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  #1   ^
Old Tue, Sep-21-04, 09:01
Zuleikaa Zuleikaa is offline
Finding the Pieces
Posts: 17,049
 
Plan: Mishmash
Stats: 365/308.0/185 Female 66
BF:
Progress: 32%
Location: Maryland, US
Default Vitamins D and A - Natural Miracles?

I wanted to share with you the information gained by my latest hobby horse, vitamin D and A supplementation. Now I've hearnd the warnings of over supplementation of these nutrients over and over so decided to see just what the actual research said about these two vitamins. I was totally amazed!!! Please do give this a read as time allows. I know it's a lot but it might be just the answer, or part of the answer, for which you're searching.

What are the diseases for which deficiencies in these vitamins have been implicated?

Vitamin D
Alcoholism
Anxiety
Arthritis
Autoimmune diseases
Birth defects
Bone diseases
Bone pain
Burning in mouth
Cancer--prostate, colon, and breast
Celiac-Sprue
Coeliac
Crohn's
Chronic Fatigue Syndrome
Chronic Pain
Cystic fibrosis
Depression
Diabetes
Diarrhea
Enzymatic diseases
Fatigue
Fibromyalgia
Graves' disease
Heart disease
Hernia
High blood pressure
Impaired wound healing
inflammatory bowel disease
Insomnia
Intestine
Irritability
Joint pain
Kidney
Liver
Lupus
Malabsorption
Multiple sclerosis
Muscle pain
Myopia
Nervousness
Obsessive Disorders
Osteomalacea
Osteoporosis
Panic Attacks
Parkinson's
Psoriasis
Rheumatoid arthritis
Rickets
Scalp sweating
Schizophrenia
Thyroid

Vitamin A
Acne
Anemia
Autoimmune diseases
Blindness
Bronchitis
Cancer—breast, cervic, and lung
Cardio vascular disease
Celiac disease
Cirrhosis
Congenital partial obstruction of the jejunum
Corneal ulcers
Chronic Fatigue Syndrome
Chronic lung disease
Cystic fibrosis
Dry Scalp
Duodenal bypass
Emphysema
Eczema
Fatigue
Fibromyalgia
Gastrointestinal problems
Giardiasis
Growth Impairment
Gulf War Syndrome
Hair and scalp problems
Hyperkaratosis
Immune diseases
Impaired healing
Infection severity (continuing and chronic)
Infertility
Insomnia
Kidney Stones
Leukemia
Melanoma
Multiple Chemical Sensitivity
Night blindness
Obstruction of the bile ducts
Pancreatic disease
Psoriasis
Respiratory infections
Rosacea
Shingles
Sprue
Thyroid
Ulcers
Urinary infections
Warts
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  #2   ^
Old Tue, Sep-21-04, 09:06
Zuleikaa Zuleikaa is offline
Finding the Pieces
Posts: 17,049
 
Plan: Mishmash
Stats: 365/308.0/185 Female 66
BF:
Progress: 32%
Location: Maryland, US
Default Vitamin D Information

Who is usually deficient in Vitamin D?

http://my.webmd.com/content/article/78/95751.htm
In the latest study, Gregory A. Plotnikoff, MD, of the University of Minnesota Medical School found a much higher incidence of vitamin D deficiency in the patients with unexplained muscle and skeletal pain than expected, regardless of their ages.

All of the African Americans, East Africans, Hispanics, and Native Americans who participated in the study were vitamin D deficient, as were all of the patients under the age of 30.

The researcher says it was a big surprise that the worst vitamin D deficiencies occurred in young people -- especially women of childbearing age. The findings are reported in the December issue of the journal Mayo Clinic Proceedings.

"The message here is that unexplained pain may very well be linked to a vitamin D deficiency," Plotnikoff tells WebMD. "My hope is that patients with unexplained pain will be tested for vitamin D status, and treated, if necessary."

http://www.washingtonpost.com/wp-dy...004May20_2.html
"The highest rate of prostate cancer is among African Americans, followed by countries in northern Europe. How are blacks like Scandinavians? They don't look alike, but in some important ways they have to be alike," said Gary G. Schwartz, a cancer researcher at Wake Forest University School of Medicine. "One way that they are alike is both groups have very low levels of vitamin D."

http://www.who.int/nut/vad.htmWhat's the minimum vitamin D necessary for good health for most people?

http://www.cholecalciferol-council....tal_illness.htm
EVIDENCE HUMANS NEED AT LEAST 3,000 IU OF VITAMIN D/DAY
Support for the growing realization that humans need a minimum of 3,000 IU of vitamin D a day (from all sources, diet, sun and supplements) includes:
1. Recent studies by Heaney et al conclude healthy men utilize between 3,000 and 5,000 IU of cholecalciferol a day, mostly from stores made by the summer sun. [21]
2. Humans living near the equator, where we evolved, have mean serum 25(OH)D levels of more than 40 ng/ml, levels requiring solar input of about 4,000 IU of vitamin D a day. [22] American lifeguards, working in swimsuits, have even higher 25(OH)D levels (64 ng/ml), in spite of temperate latitudes.[23]
3. In 2003, Gomez recently produced evidence that excessive secretion of the parathyroid gland (secondary hyperparathyroidism) is almost nonexistent when 25(OH)D levels exceed 30 ng/ml (requiring 3,000 IU of D a day). [24] Vieth cited six studies that concluded, if the aim is to keep parathyroid hormone concentrations low, 25(OH)D levels should exceed 28 ng/ml (70 nmol/L). [25]
4. Heaney and his colleagues recently showed that calcium absorption increases as 25(OH)D blood levels increase.[26] With blood levels of 34 ng/ml (equivalent to about 3,000 IU/day total intake), calcium absorption was 65% higher than when levels are 20 ng/ml. This implies that part of the reason humans need to take so much extra calcium is because there is widespread deficiency of vitamin D. when speaking of 25(OH)D blood levels, the authors were blunt, “We conclude that the lower end of the current reference range is set too low.”
5. Blood pressure is reduced significantly by ultraviolet radiation comparable to about oral intake of 3,000 IU of vitamin D a day [27] but blood pressure is not routinely reduced by small amounts of vitamin D.[28]
6. Daily doses of 2,500 IU of vitamin D helped rheumatoid arthritis [29] but small amounts did not.[30]
7. Infants receiving 2,000 IU a vitamin D a day were almost fully protected (relative risk 0.12) from developing type 1 diabetes 30 years later.[31]
8. 5,000 IU of vitamin D a day, along with calcium and magnesium, decreased the relapse rate in multiple sclerosis patients.[32] Multiple sclerosis is rare around the equator.[33]
9. To our knowledge, all studies of vitamin D and fractures demonstrate reduced fracture rates, as long as 25(OH)D levels increased to more than 40 ng/ml after treatment. [34] [35]
10. Breast milk (nature’s perfect food) is deficient in vitamin D. Does this mean Paleolithic humans were supposed to expose their young to the sun (and thus to predators)? Hollis recently discovered that breast-feeding mothers need 4,000 units of vitamin D a day to sustain themselves and their infant.[36] 2,000 units a day was not effective. It seems likely to the authors that the lack of vitamin D in human breast milk is due to widespread deficiency in mothers.[37]
10. Humans make thousands of units of vitamin D within minutes of whole body exposure to sunlight. From what we know of nature, it is unlikely such a system evolved by chance.

The definitive answer on vitamin D dosage

http://www.cure-guide.com/Natural_H.../vitamin_d.html

Babies

Babies' vitamin D stores at birth can be increased if their mothers have had adequate exposure to sunlight and/or adequate vitamin D intake during their pregnancies. Vitamin D is essential for bone growth in infancy and throughout childhood. The two reliable and safe sources of vitamin D for babies are sunlight and cod liver oil.

According to Barber and Purnell-O'Neal writing in Mothering Magazine, "a baby in a diaper needs a total of only 30 minutes of sunlight a week - less than five minutes a day. Fully clothed and without a hat, a baby would need two hours of sunlight a week, or about 20 minutes a day. Medium to darker skin tones need a little more time in the sun (Barber & Purnell-O'Neal, 2003)."

Avoid prolonged exposure to bright sunlight because of the danger of sunburn. Babies will get enough vitamin D if they have access to a bit of sun each day.

Babies that reside in North America and Europe may need vitamin D supplementation during the colder months of the year when sun exposure is not possible and weather prevents adequate exposure to the healthy rays of the sun.

Cod liver oil will provide vitamin D, vitamin A, and the omega-3 fats that stimulate brain development. Give one teaspoon for each 50 pounds of weight. A baby that weighs 10 pounds should get ¼ teaspoon, and a baby that weighs 20 pounds should get a little less than ½ teaspoon per day in the winter months. Use a source of cod liver oil that has been tested for contaminants (such as Carlson's brand). In the late spring through early autumn, give 100 mg of the omega-3 fat DHA from algae (Neuromins) or a fish oil supplement without vitamin D to babies who are eating solids. Babies that are solely breastfed do not need additional DHA if their mothers have an adequate intake of omega-3 fats, such as a fish oil or cod liver oil supplement. Breast milk normally has high levels of DHA, which can be increased by taking an omega-3 supplement.

==================================
Adults

It is safe to obtain vitamin D from the sun's UVB radiation or from foods. Vitamin D3 (cholecalciferol) is found in eggs, animal fat, and cod liver oil. Do not eat fish to secure vitamin D in your diet. The fish available to us is not safe to eat. Vitamin D2 (ergocalciferol) found in plants is less biologically active and is toxic at high dose levels, above 10,000 units per day.

Have your vitamin D levels tested before supplementing your diet. The correct test is 25-hydroxyvitamin D. Normal values, according to Dr. Joseph Mercola, are 45-55 ng/ml (115-140 nmol/l). Most lab reference ranges are too low.

Do not attempt to supplement your diet with significant amounts of vitamin D without adequate testing. Krispin Sullivan, author of the forthcoming vitamin D book Naked at Noon recommends frequent testing. "Minimum testing should not be less than every three months the first year and six months the second and third years. Elevated 25(OH)D may not show up in a blood test until as long as 2-3 years after starting an excessive dose" (www.sunlightandvitamind.com).

The typical vitamin D dosage is 2,000-3,000 IU for a 150 pound person, or 1 teaspoon of cod liver oil for each 50 pounds of body weight. Sullivan recommends seeking out a health care provider knowledgeable in vitamin D supplementation. Use cod liver oil during the winter months and switch to a fish oil omega-3 supplement during months when exposed to sunshine is possible.

Do not use a daily sunscreen. Reserve sunscreen use for the prevention of sunburn during midday exposure in bright sunlight, when swimming, at the beach, and during snow sports. Then use only zinc oxide and titanium dioxide sunscreens either in a cream (Lavera, Dr. Hauschka, etc.) or micronized powder (ColorScience).

Before considering supplementation with vitamin D, it would be wise to have your vitamin D level tested. This is best done from a nutritionally oriented physician. It is very important that they order the correct test. The advantage of having your medical doctor perform the test is that it will usually be covered by your medical insurance.
Eventually, Krispin Sullivan, my nutritionist mentor in vitamin D, hopes to have an inexpensive saliva hormone test that you will be able to do through the mail. In the meantime, the blood test is the best route to monitor vitamin D levels at this time.
Don't Be Fooled -- Order the Correct Test
There are two vitamin D tests -- 1,25(OH)D and 25(OH)D.
25(OH)D is the better marker of overall D status. It is this marker that is most strongly associated with overall health.
The correct test is 25(OH)D, also called 25-hydroxyvitamin D
Please note the difference between normal and optimal. We don't want to be average here; we want to be optimally healthy.
Primitive man likely developed in tropical and sub-tropical conditions with large exposure to UV-B and its secondary consequence to skin exposure, vitamin D.
Primitive environmental availability of a nutrient does not necessarily establish the higher requirements, but these exposures would have influenced the evolution of the relevant physiology, and such concentrations should at least be considered presumptively acceptable.
Some experts may disagree with the following healthy ranges, but they are taken from healthy people from the tropical or subtropical parts of the world where they are receiving healthy sun exposures. It seems more than reasonable to assume that these values are in fact reflective of an optimal human requirement.
Dr. Michael Hollick is one of the top vitamin D researchers in the world and he has been advocating higher reference ranges, though not as high as the ones suggested here.
(Holick MF. Calcium and Vitamin D. Diagnostics and Therapeutics. Clin Lab Med. 2000 Sep;20(3):569-90)
Optimal 25-hydroxyvitamin D values are:
45-50 ng/ml or
115-128 nmol/l Normal 25-hydroxyvitamin D lab values are:
20-56 ng/ml
50-140 nmol/l
Your vitamin D level should NEVER be below 32 ng/ml. Any levels below 20 ng/ml are considered serious defiency states and will increase your risk of breast and prostate cancer and autoimmune diseases like MS and rheumatoid arthritis.
If you have the above test performed, please recognize that many commercial labs are using the older dated reference ranges. The above values are the newest ones from the clinical research.

Make Sure Your Lab Uses the Correct Assay
There are a number of different companies that have FDA approval to perform vitamin D testing. The gold standard company though is Diasorin. Quest labs is the largest commercial lab in the US and they use this company to measure 25 hydroxy D levels. However, many other commercial labs don’t. So if you do not have your test done at Quest labs please contact the lab directly to find out which assay is being used. Your test results will not be accurate and you can not use the values in the table above unless the D is measured with a Diasorin assay. The extra hassle is definitely worth it, believe me. You will only need to do this once though, as the labs do not switch assays. However, if your lab is not using the Diasorin assay you could ask them to switch to the gold standard.

How To Dose Your Vitamin D Once You Know Your Levels
Vitamin D is a fat soluble vitamin and can be quite toxic. Once you have vitamin D toxicity you can't easily turn it around.
So don't even think of starting this program unless you have your blood levels checked. Many of you may choose to ignore this warning, but I am telling you in plain simple English, that while vitamin D has enormous potential for improving your health, it has nearly equal potential to worsen it, if you use it improperly.
For safety purposes it is advisable to optimize your vitamin D levels only with the help of a trained health care professional. The exact protocol to optimize your vitamin D levels will be in Krispin Sullivan's upcoming book Naked at Noon. The book will have far more information than is in this brief review and will further highlight the importance of testing.
If you need to know this information before her book is published a preliminary copy of her vitamin D research is available on her Web site. While she has an e-mail listed on her site, please understand that she doesn't have time to respond to personal e-mails or her book will never be finished.
Krispin Sullivan and I share the same passion--seeking to help large numbers of people regain their health with inexpensive nutritional therapies. She has researched this subject for a number of years and, to the best of my knowledge, is one of the most experienced clinicians in this area. She has provided me with much of the foundational background for this review, and I am very grateful for her willingness to bring me up to speed in, not only this area, but also omega-3 nutrition and vitamin K.

Sunlight Is the Ideal Source of Vitamin D
Ideally, the best place to get vitamin D is from your skin being exposed to the UV-B that is in normal sunlight. Vitamin D from sunlight, or supplements, acts as a pro-hormone, rapidly converting into 25-hydroxyvitamin D.
Many experts believe that there is no harm in the vitamin D concentrations associated with sun exposure, and that such levels are probably optimal for human health.
Unfortunately, the amount of sun reaching most of the U.S. is only sufficient to generate a vitamin D response for about three months of the year.
Now, I can just hear scores of you getting alarmed that this recommendation will increase your risk of skin cancer. Well folks, nothing could be further from the truth.
I will provide all of the documentation and scientific research to support this assertion in future issues. But, I am convinced beyond any shadow of a doubt that as long as you avoid being sunburned, sun exposure at noon on unexposed skin is one of the healthiest things you can do for your body.
Most of us just don't live far south enough, or high enough in the mountains, to allow more UV-B to reach our skins. So, for those times of the year when access to the proper amount of sun is not possible, you will want to consider the cod liver oil recommendations above.

Ultraviolet-B Is What Generates Vitamin D In Your Skin
Ultraviolet (UV) light is divided into 3 bands, or wavelength ranges, which are referred to as UV-A, UV-B and UV-C.
UV-B is sometimes called the "burning ray." It's the primary cause of sunburn caused by overexposure to sunlight. However, UV-B sunlight produces vitamin D on the skin. The amount produced depends on exposure time, latitude and altitude of location, amount of skin surface exposed, skin pigmentation and season.
UV-B also stimulates the production of MSH, an important hormone in weight loss, energy production, and in giving you that wonderful tanned appearance.
However, UV-B does not penetrate very deeply into the skin. The darker the pigmentation or more tanned the skin, the less UV-B penetrates. Window glass allows only 5% of the UV-B light range that produces D to get into your home or auto.
The timing of your sun exposure is also a major factor. Sun exposure must take place when UV-B is present. The forthcoming UV-B meter, discussed below, should greatly aid in this assessment.

The actual dosing of the sun exposure is quite complex, since it involves knowing the amount of UV-B and one's skin color.
This doesn't sound very complex, but the amount of UV-B is not a constant. It is a major variable and is influenced by a number of factors:
• Latitude -- the further north you are the less there is
• Time of Year -- virtually none available in winter in continental U.S.
• Clouds -- can block UV-B
• Pollution -- smog and ozone can block UV-B
• Altitude -- the higher up you are the more UV-B reaches you
I am working with a company now to bring a very inexpensive UV-B meter so you can know exactly how much sunlight you need on any given day to generate an optimum vitamin D exposure. I hope to have that UV-B meter available later this year so you can use it to time your dose of sun exposure.
It is important to know the level of UV-B exposure. Unlike the typical American strategy, more is better, that is not the case for UV-B exposure. Longer exposure will not increase vitamin D production, but will increase the danger of skin damage and possible skin cancer.

Major Caution: Avoid Sunburn
Again, it is important to stress that you should never get burned and should only implement sun exposure very gradually.
While we all benefit from regular exposure to sun, it is important to recognize that you should always limit your exposure so that you don't get burnt. Sunburn has been clearly related to an increased risk of skin cancer.
Interestingly, if you don't get sunburned and actually have regular sun exposure, you will have a decreased risk of the dangerous skin cancer, melanoma.
However, don't let dermatologists scare you. We all need sun. It is very similar to water. Just because you can drown while swimming, doesn't mean you should never drink water or swim in it. Similarly, as long as we avoid sun exposure that will cause burning, it will help improve our health.
Later this year I will provide all the scientific documentation for this. It is a complex issue though. Skin cancer is largely related to the over abundance of omega 6 oils that we have in this country. When sunlight hits these fats it can convert them to cancer causing molecules, and if one is not healthy, these cells can go on to developing cancer.
This cancerous transformation doesn't happen with omega three fats. So, changing the ratio of omega 3 to omega 6 oils in your diet is one the keys to prevent this. The best sources of omega three fat would be cod liver oil and grass fed animals like beef.

Remember: Don't Ever Get Sun Burned
It is also important to point out the obvious. Fair skinned individuals need far less exposure to receive their dose of sun to produce vitamin D. Lighter skin allows for greater penetration of UV-B, leading to higher levels of D.
African Americans however, would need considerably more sun to generate vitamin D. This is one of the reasons why breast and prostate cancers are so much higher in Africans who are living in temperate climates. They just aren't able to get enough sun to generate vitamin D. In fact, in the Northern U.S. cities, they will find it impossible to get adequate D from sunlight in any season.
Elderly individuals will also have a great difficulty getting enough vitamin D from sun exposure, since an enzyme in their skin decreases with degenerative aging and, as a result, their skin has a limited capacity for producing vitamin D.
Interestingly, it is impossible to get vitamin D toxicity from too much sun exposure. Your body just won't let it happen. That is why receiving your vitamin D from the sun is the best option if possible.

Ultraviolet exposure beyond the minimal dose required to produce skin redness, does not increase vitamin D production any further.
An equilibrium occurs in white skin within 20 min of ultraviolet exposure, in which further increases in vitamin D is not possible, since the ultraviolet light will actually start to degrade the vitamin D.
It can take 3-6 times longer for pigmented skin to reach the equilibrium concentration of skin previtamin D. However, skin pigmentation does not affect the amount of vitamin D that can be obtained through sunshine exposure.
It is commonly thought that only occasional exposure of the face and hands to sunlight is "sufficient" for vitamin D nutrition. Indeed, this exposure can provide 200-400 IU vitamin D during those months when the appropriate sunlight is available.
Supplemental Vitamin D
Unfortunately the vast majority of us living in the U.S. just do not have access to the proper amount of sun most of the year. Even if the sun is out there, most of us are working during the week and don't have time to go out and capture some sunlight on our skins.
So, that leaves supplementation as the only practical option for most of us.

Vitamin D Toxicity
First, let me state that there are two types of vitamin D supplements: vitamin D3 (cholecalciferol) which comes from fish oil and plant source D2 (ergocalciferol) which is found in fortified foods and some supplements. D2, found in plants and made active by irradiation, is less biologically active.
Vitamin D3 is found in eggs, organ meats, animal fat, cod liver oil and fish. It is the equivalent to the vitamin D3 formed on our skins from UV-B.
You should stay away from the synthetic D2 as it is the one that has been shown to have toxicity at the higher dose ranges. You will only want to use vitamin D3.
There are newer reasons why vitamin D2 has a greater potential for harm. First, vitamin D binding protein has a weaker affinity for the vitamin D2 metabolites than vitamin D3. Second, unique biologically active metabolites are produced in humans from vitamin D2, but there are no analogous metabolites derived from vitamin D3.
There is no doubt that vitamin D2 is a synthetic analogue of vitamin D, with different characteristics. It is inappropriate to regard vitamin D2 as a vitamin. Future research into the toxicity of this vitamin needs to focus on vitamin D3 as being something distinct from vitamin D2, for which almost all our current toxicity data relate to.
Even without careful attention to the type of vitamin D being used, a recent expert review on vitamin D was unable to find any published evidence of vitamin D toxicity in adults from an intake of 10,000 IU per day that was verified by the blood 25(OH)D concentration.

People Who Should Not Take Supplemental Vitamin D
Some patients with sarcoidosis, tuberculosis, or lymphoma become hypercalcemic in response to any increase in vitamin D nutrition. For these persons, it may be wise to avoid any dietary or environmental sources of vitamin D, unless they are carefully monitored with serum calcium and 25(OH)D levels.

Although Mercola cautions about vitamin D toxicity, he later recants by this:

http://www.mercola.com/2003/dec/27/vitamin_d_quiz.htm

How Much Vitamin D is Too Much? Take This Vitamin D Quiz to Find Out!

Dr. Mercola's Comment:

There is much confusion about vitamin D and vitamin D toxicity. I encourage you to take the quiz and even pass it along to your doctor, as very few U.S. physicians are aware of vitamin D’s importance.

Winter is the time of year when most of us in the United States need to be very diligent about keeping our vitamin D levels within optimal levels. I recommend that most take a high-quality cod liver oil, which is an excellent source of vitamin D, regularly from fall until early spring. However, it is essential to understand that in order to know how much vitamin D you should be taking, you should get your blood level checked. If you use beneficial products like cod liver oil without doing blood tests for vitamin D levels, you should keep the dose at one to two teaspoons per day to prevent overdosing.

This is a major point: excess vitamin D will cause, not prevent, osteoporosis and hardening of your arteries. Please be very careful with cod liver oil. If you are unable to obtain vitamin D testing, then please do not exceed one to two teaspoons of cod liver oil. So please do yourself a favor--read the article on vitamin D testing and be sure to have your level measured. As I mentioned above, nearly all physicians are not aware how to have this checked and how to interpret the normal reference ranges, so I encourage you to print out the article on vitamin D testing not only for your own records but also for your doctor so he or she can become aware of this vitally important nutrient.

The Vitamin D Council, the non-profit group that contributed the excellent quiz below, is another great resource for vitamin D information. The Vitamin D Council is a group of citizens concerned about vitamin D deficiency and the diseases associated with that deficiency. I encourage you to check out their website and sign up for their informative newsletter. Their goal is an important one: to draw attention to the problem of vitamin D deficiency through the education of professionals, the media, government officials and average citizens.


--------------------------------------------------------------------------------

By John Jacob Cannell, M.D.
Executive director of The Vitamin D Council

1. If an otherwise healthy adult tried to kill himself by taking an entire bottle (250 capsules) of 1,000 iu cholecalciferol, which of the following would happen?

a) The person would die within 24 hours from severe hypercalcemia and widespread calcinosis.
b) If the person received intensive treatment for hypercalcemia he may survive.
c) Hypercalcemia would be severe but require only supportive treatment.
d) Such doses are called "Stoss" therapy and are occasionally used therapeutically although they do not replicate normal physiology. As most Americans are vitamin D deficient, such a one-time dose would probably be a health benefit for the majority of Americans.

The correct answer is d. One of the most recent examples is the use of stoss therapy to reduce fracture rates in the elderly (100,000 IU of oral cholecalciferol every four months for five years) by Dr. Trivedi and colleagues (University of Cambridge School of Clinical Medicine) published in the British Medical Journal. How high do you think average 25-hydroxyvitamin D levels were in the subjects after they received 100,000 IU of cholecalciferol every four months for five years? Answer: about 29 ng/ml, still mildly deficient! (Source)

2. Acute poisoning leading to rapid death from ingestion of vitamin d capsules (successful suicide attempt),

a) Has frequently been reported in the literature.
b) Has occasionally been reported in the literature
c) Has never been reported in the literature.

The answer is C, as far as we know. If you know of a report of a successful suicide attempt, accidental death or murder from overdosing on vitamin D supplements, let us know. We do know of one interesting case that demonstrates the relative safety of vitamin D. Industrial strength crystalline vitamin D was added to table sugar, either by accident or on purpose. The two men poisoned were getting about 1,700,000 IU of cholecalciferol every day for seven months. Again, they were getting at least, 1,700,000 units [440 times the Institute of Medicine's toxicity warning (LOAEL)] every day for seven months! Both got very sick but recovered. (Source)

3. True of false: water has a higher (safer) therapeutic index (the median lethal dose divided by the median effective dose) than cholecalciferol?

a) True
b) False
c) About the same

The answer is b. Although exact human studies have never been done for obvious ethical reasons, water intoxication leading to hyponatremia, cerebral edema and occasional death is common in psychiatric populations and may become evident if one drank 80 glasses of water a day, instead of eight. Heaney, et al, recently showed healthy humans utilize about 4,000 IU of cholecalciferol a day, if they can get it. 40,000 IU a day is certainly not acutely toxic. In fact, some research reported that young white humans get up to 50,000 IU from one full body summer sun exposure. (Source)

4. If a person totally avoided the sun and regularly took two standard multivitamins a day for several years, each containing 400 iu of ergocalciferol, as his sole source of vitamin d, he would,

a) Rapidly become vitamin D toxic and require medical attention for symptoms of hypercalcemia.
b) Slowly become vitamin D toxic and eventually become symptomatic.
c) Slowly develop hypervitaminosis D but remain asymptomatic.
d) Obtain a healthful vitamin D blood level.
e) Inexorably become vitamin D deficient.

The answer is e. Two standard multivitamins contain 800 IU of ergocalciferol, equivalent to about 500 IU of cholecalciferol. If you totally avoided the sun, as many dermatologists routinely recommend with impunity (so far), one would have enough vitamin D to prevent rickets and osteomalacia but would still have a suboptimal 25-hydroxyvitamin D and thus be at risk to develop numerous other chronic inflammatory diseases, not just osteoporosis. For a review of such illnesses, see Zittermann. (Source)

The key is "totally avoided the sun." Remember, most people get 90 percent of their vitamin D requirement from very casual sun exposure, like the sunlight that strikes the uncovered and unsunblocked face, arms and hands when you walk to your car. Vitamin D production in the skin is that fast. Of course, some people follow their doctor's advice and take obsessive steps to prevent sunlight from ever striking their unprotected skin. A host of chronic inflammatory diseases may await the patients who follow such advice, just as trial lawyers may await the doctors that give it.

5. Of the three medications listed below, which is the safest in overdose?

a) Vitamin D (250 of the 1,000 IU capsules)
b) Aspirin (250 of the 325 mg tablets)
c) Tylenol (250 of the 500 mg tablets)

The answer is a. In fact 250,000 IU of vitamin D at one time is used as "stoss" therapy, especially in Europe. For a review of many such studies and the doses needed to achieve toxic 25-hydroxyvitamin D levels, see Vieth. (Source)

6. Which drug has the highest (safest) therapeutic index?

a) Depakote
b) Lithium
c) Coumadin
d) Dilantin
e) Synthroid
f) Theophylline
g) Cholecalciferol

The answer is g. All of the medication listed except cholecalciferol have narrow therapeutic indices and can easily cause death in overdose. Such is not true for vitamin D and, because of the huge number of capsules needed, is not likely unless one has the industrial strength compound. See below for a sample calculation.

7. In 1997, adams and lee wrote a widely publicized paper about vitamin d toxicity in the annals of internal medicine. The adams and lee paper was accompanied by a stern editorial warning of the dangers of vitamin d written by marriott of the national institute of health. The three authors,

a) Correctly diagnosed all five of the patients
b) Were thanked by nationally acclaimed vitamin D scientists for their contributions to understanding vitamin D toxicity.
c) Showed frightening ignorance about vitamin D toxicity and appeared not to know the difference between the two standard deviation upper limit of a Gaussian distribution and levels known to reflect vitamin D toxicity.

The Adams and Lee paper and the editorial by Dr. Marriott are a continued embarrassment to the usually stellar Annals of Internal Medicine. However, the papers are instructive in that they remind us that otherwise educated and intelligent research physicians can confuse the two standard deviation upper limits of a Gaussian distribution with toxicity. For a more detailed critique, as well as several other problematic articles about vitamin D, see this link.

8. By sunbathing for a few minutes in the noonday summer sun, one can easily obtain five times the vitamin d toxicity warning (lowest observed adverse effects level or loael) of the institute of medicine's food and nutrition board.

a) True
b) False

The answer is a, at least for young whites. The IOM lists the Lowest Observed Adverse Effects Level (LOAEL) as 3800 IU for vitamin D. Studies show young whites can make between 10,000 to 25,000 IU in a single, relatively brief, sun exposure. Numerous factors affect the body's ability to make such high amounts of cholecalciferol, with age, race, latitude, clothing, season and sunblock being the main factors. (Source)

9. If humans are twice as sensitive as the most sensitive mammal tested (male rats), then a 110-pound human would have to injest 88,000 capsules (352 bottles containing 250 of the 1,000 iu capsules) of cholecalciferol in order to have a 50 percent chance of dying (ld50) from an acute overdose.

a) True
b) False

False, about 168 bottles would do it. The LD50 for male rats (the most sensitive mammal tested) is 42 mg/kg. If humans were twice as sensitive that would be an LD50 of 21mg/kg or 21,000 ug/kg or 1,050,000 ug for a 50 kg human which is 42,000,000 units or 42,000 capsules or 168 bottles of the 250 capsules of 1,000 IU cholecalciferol. [Dorman DC (1990) Toxicology of selected pesticides, drugs, and chemicals. Anticoagulant, cholecalciferol, and bromethalin-based rodenticides. Vet Clin North Am Small Anim Pract 20(2):339-352].

10) As most american blacks suffer from vitamin d deficiency, some black activists feel unwarranted fear and scare techniques about vitamin d toxicity may be racially motivated. That is, racists may be intentionally repeating and promulgating vitamin d toxicity scares in order to prevent relevant government agencies from dealing with the problem of widespread vitamin d deficiency in the black community.

a) True
b) False

True. The recent NIH conference on vitamin D was most interesting in this regard. Very few Blacks were attendees but several were helping with registration. As the conference progressed into the second day, Blacks helping with registration began to listen to the lectures and became increasingly angry as speaker after speaker pointed out how vitamin D deficiency adversely impacts the black community. One young black man told a sad story of how his infant son was recently diagnosed with rickets. Although the 1997 Food and Nutrition Board was an all-white board, most of the Blacks were angry that nothing is being done currently.

Certainly, it is true that one of the most effective ways to paralyze the government into continued inaction on the pandemic of vitamin D deficiency would be to raise false and frightening toxicity fears. However, remember that it is easy to suspect vast conspiracies, but in the end it is usually simple incompetence. That is certainly true of the mistakes I've made in my life.

11. In the most recent case of vitamin d toxicity described in the literature, a man recovered uneventfully after taking a health supplement every day for two years that contained 156,000 iu of cholecalciferol.

a) True
b) False

True. Actually, it is likely he took more than that. An industrial manufacturing error was implicated. Such reports help confirm what is known from animal data and that is that it takes a lot of vitamin D to hurt you, but it can be done. (Source)

12. One of the world's foremost authorities on vitamin d metabolism and physiology recently said, "worrying about vitamin d toxicity is like worrying about drowning when you are dying of thirst."

a) True
b) False

True. The quote is from one of the vitamin D scientists listed below. One of the problems is that there are so few vitamin D scientists in the world, that misconceptions, especially about toxicity, are the rule rather than the exception, even among medical researchers.

In 1999, Dr. Reinhold Vieth, perhaps the world's leading expert on vitamin D toxicity and metabolism, wrote a systematic and scholarly review of the world's literature debunking the hysteria surrounding fears of vitamin D toxicity. (Source)

Later, Vieth demonstrated the safety of daily dosing with 4,000 IU of cholecalciferol, a dose that exceeded the current toxicity warnings of the IOM's FNB. (Source)

Two years later, Heaney, et al, demonstrated the safety of doses up to 10,000 IU a day while also demonstrating for the first time that healthy humans utilize 3,000 to 5,000 IU of cholecalciferol a day (10 times the Institute of Medicine Food and Nutrition Board's current recommended Adequate Intake). What the human body does with such high amounts of cholecalciferol remains unknown, but we suspect Nature has a plan. (Source)

In a reply to critics of his paper, Vieth challenged anyone in the scientific community to present even a single case of vitamin D toxicity in adults from ingestion of up to 1,000 ug (40,000 IU) a day of cholecalciferol saying, "I welcome any discussion of evidence of harm with vitamin D3 (not D2) in adults at doses <1,000 ug/d." Vieth's challenge remains unanswered and his work remains unrefuted. (Source)


--------------------------------------------------------------------------------
Related Articles:
RDAs of Vitamin D Far Too Low

Millions of U.S. Youth at Risk of Vitamin D Deficiency

Vitamin D for Cancer

Milk Not Useful in Raising Your Vitamin D Levels

Vitamin D Treats Congestive Heart Failure

Even Breastfed Babies Deficient in Vitamin D

Another concuring view quoting actual studies:
http://stopcancer.com/Barefoot&DeWi...cerDefense2.htm

Vitamin D God Versus the A.M.A. by Robert Barefoot

Today, as never before, the American public is being bombarded with a barrage of medical misinformation designed to make the richest industry, drugs and pharmaceuticals, even richer. The statements either emanate (come out from a source) or are being supported by the medical prestigious (marked by illusion or trickery) American Medical Association, commonly known as the AMA. The statements, when viewed up close, appear to be made for the protection of the public; however, when viewed as a whole form at a distance, they can be interpreted as having the opposite effect. For example, "You don't need your gall bladder", even though it serves a useful biological function. Not only does this statement imply that God did not know what he was doing when he created man, but also the statement gives justification for the multi billion dollar assembly line removal of over 1,000,000 gall bladders a year in America. Another example is, "The sun is bad for you, it can cause cancer." Not only does this statement, once again, imply that God made a mistake when he created the solar system, but it also provides support for the multi billion dollar sun block industry. The tragedy is that, not only does the sun help the plants and animals to flourish, there is massive scientific evidence to show that the human body needs sunshine to provide good health. Although there are dozens more examples of statements inferring that the AMA is right and God is wrong, the most devastating to human health is the statement that Vitamin-D in excess is toxic. The measure of excess is their Recommended Daily Allowance, or RDA, which, in the case of vitamin-D, is 400 International Units (I U's) daily. Although 400 may sound like a big number, 400 IUs of vitamin-D is less than 0.01 milligrams. For those who do not understand just what a milligram is, a grain of salt weighs several milligrams. Thus the yearly RDA for vitamin-D designed by God is less than a grain of salt, and anything in excess of this, according to the AMA, "may be toxic". To understand why this ridiculously low recommended consumption is devastating to human health, one must review the history of vitamin-D.


To begin with, toxicity is defined as "the ability of a substance to cause injury to living tissue once it reaches susceptible site in or on the body". Based on this definition, almost all drugs are toxic. However, when a doctor tells a patient that something "is toxic", almost always, the patient believes that the doctor means that "it can kill you". Unfortunately, the doctors common referral to "too much" vitamins and minerals as toxic is more than often interpreted as meaning that they can be "lethal". Both history and scientific studies have shown this not to be true when taken in reasonable amounts. The question then becomes, "just what is a reasonable amount and what is too much?". Nutritionists believe that the amounts that should be consumed are often 2 to 100 times the recommended daily allowance (RDA). Scientific testing has shown that such amounts are both safe and effective. However, when seeking justification for the rash toxic statements, modern medicine resorts to studies where the amounts consumed are tens of thousands of times the RDA. Of course this is unreasonable if logic were to prevail.


When one, studies the massive scientific documentation on tests carried out by world recognized scientists, one has to almost conclude that their has been a conspiracy to maintain the myth that vitamins and minerals can be harmful to your health. To present this information in a form that the public could understand would take several books. However, because of the importance of vitamin-D in the prevention of disease and aging, and because of the fact that, except for health stores, it basically remains off of the shelves, and when found, it is only in tiny amounts too small to be effective. Examples of such studies are as follows:


After vitamin-D was removed from the market following the toxic effects that massive doses had on seven medical students, the public, who commonly took mega doses (millions of I.U.s) daily and claimed dramatic health benefits, demanded a fair study. One of the first and largest, Further Studies on Intoxication With Vitamin-D, was done by the University of Illinois, Chicago, Annuals of Internal Medicine, Volume 10, Number 7, January 1937, and took nine years to complete. They concluded that " Early experience with impure preparations of Vitamin D has lead to a get deal of misunderstanding and fear of over dosage on the part of those who have little acquaintance with the fundamental mechanisms involved. Suffice it to say that most of the earlier work must be disregarded. They also noted that both human subjects and dogs generally survive the administration of 20,000 I.U. per kilogram (14,545,000 I.U for a 160 pound man) per day for indefinite periods without intoxication." They further concluded that, "In view of the extensive experience in administration of vitamin-D to human subjects with a relatively low incidence of toxicity, and the correlation of the results of animal experiments with the observations on human subjects, we believe that the burden of proof now rests on those who maintain the undesirability of the use of this form (high daily doses of Vitamin D) of therapy.


Another study, A Preliminary Report on Activated Ergosterol (A form of High Dosage Vitamin-D in the Treatment of Chronic Arthritis), by G. Garfield Snyder, M.D., F.A.C.P., Willard H. Squires, M.D., F.A.C.P., New York State Journal of Medicine, May 1, 1940, pp 708-719, which used doses over 750 times the RDA of vitamin-D, concluded " We are inclined to agree with Reed Struck and Streck that the hazards of toxicity in high dose vitamin-D therapy have been greatly exaggerated” as "the degree of clinical improvement has been marked and sustained” and “No serious toxic manifestations were encountered.”


Another study, Follow-up Study of Arthritic Patients Treated with Activated Vaporized Sterol, by R. Garfield Snyder, M.D., F.A.C.P., Willard H. Squires, M.D., F.A.C.P., New York State journal of Medicine, December, 1941 concluded that "the use of high doses of activated Vitamin-D is not associated with any more danger than is usually encountered with other accepted forms of therapy.”

The study, Comparative Therapeutic Value and Toxicity of Various Types of Vitamin-D by Chapman Reynolds, M. D. , Louisiana State University School of Medicine, The Journal Lancet, Minneapolis, October, 1942, Vol LXII, No.10, page 372, reported that the treatment of arthritis with massive doses (thousands of times the minimum treatment of 10,000 IU) of vitamin-D led to favorable results with no toxic reactions. This study also shows that the original toxic effects that resulted form taking thousands of times the minimal requirement (over 250,000 times the current RDA), were not caused by the vitamin-D but were caused by the impurities of using the pre 1932 solvent extraction procedure to produce the vitamin-D. It also concluded that the same amounts of the newer and cleaner form of vitamin-D produced by the Whittier process, used exclusively after 1932, was both non-toxic and beneficial to health.


In the study, The treatment of Arthritis By Electrically Activated Baporized Ergosterol, by G. Norris, M.D., Rheumatism, July 1947, pages 56-60, vitarnin-D in massive dosage is of great value in the treatment of arthritis, and that toxic effects are so rare or so temporary as to constitute no obstacle to its use.


The forgoing were just a few of the many prestigious scientific reports done by credible world renown scientists working in famous research institutions who gave powerful evidence to the fact that vitamin-D was not toxic. Many more credible reports exist which demonstrate the benefits of vitamin-D to human health, and can be found in the book The Calcium Factor by Carl Reich, M.D. and Robert Barefoot, Chemist. The few negative reports that could be found did not stand the test of scientific credibility, such as clinical research done in the name of scientific research by doctors experimenting on only a few patients for a short time and with no quality control. Unfortunately, they are telling there leaders in the AMA what they want to hear, so the real massive scientific research which contradicts these feeble findings is removed from the doctor's vision. Nevertheless, vitamin-D, designed by God, has been scientifically proven to be both beneficial to human health and non toxic.

The conclusion of an actual study of the safety of vit D3 at different levels
http://www.direct-ms.org/articles/V...SafetyStudy.pdf
Throughout the history of vitamin D supplementation in North America, high-dose preparations of the vitamin D2 form have generally been used. Vitamin D3 is common in lower-dose regimens, but in some parts of the world vitamin D2 is the only form licensed for use. In terms of rickets prevention, research from the 1930s was inconclusive at detecting a difference in efficacy between the 2 forms of vitamin D; therefore, pharmacopoeias continue to regard vitamin D2 as being equivalent to vitamin D3,
292 VIETH ET AL FIGURE 3. Total serum calcium concentrations and urinary calcium-creatinine excretion ratios at baseline (0 mo) and during supplementation with 25 (A and C) and 100 (B and D) g vitamin D3/d. The heavy line in each panel is the nonparametric, locally weighted regression and smoothing scatter plot. The dotted lines reflect the upper limit of the central 95% CI for the mean change. The value of each dotted line was calculated by adding the upper limit value (97.5%) for the mean change from baseline at each time point to the mean baseline value (month 0) for each group (repeated-measures
ANOVA followed by Dunnett’s test). even though the latter form is more effective at raising serum
25(OH)D concentrations (20). What seems to have been forgotten nis that the literature of half a century ago established that, at high doses, there was a greater risk of toxicity with what was called “the purely artificial” compound, vitamin D2 (38–40). One explanation for the difference in toxicity was the poorer stability and greater impurity of vitamin D2 than of vitamin D3 preparations (38). There are newer reasons why vitamin D2 has a greater potential for harm. First, vitamin D binding protein has a weaker
affinity for the vitamin D2 metabolites than for 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (41–43). This means that the proportions of free 25-hydroxyvitamin D2 and 1,25-dihydroxyvitamin
D2 are higher and more biologically available. Second, unique biologically active metabolites are produced from vitamin D2 in humans and there are no analogous metabolites derived from vitamin D3 (44). There is no doubt that vitamin D2 is a synthetic analogue of vitamin D, with different haracteristics.
It is an anachronism to regard vitamin D2 as a vitamin. Future research into the toxicology of this vitamin needs to focus on vitamin D3 as being something distinct from vitamin D2, for which almost all our current toxicity data relate to. The working definition of the recommended dietary allowance has been to ensure “levels of intake of essential nutrients considered, in the judgment of the Food and Nutrition Board on the basis of available scientific knowledge, to be adequate to meet the known nutritional needs of practically all healthy persons” (2, 6). For vitamin D, the relevant question could be, what 25(OH)D
concentration is desirable and how much vitamin D is needed to ensure that most adults attain this intake (45)? We did not measure PTH in this study, so we cannot address the question of what the desirable vitamin D intake is. However, the present results do provide insights into the lowest 25(OH)D concentrations that can be reasonably ensured in adults consuming 25 and 100 g vitamin D3/d. The 25- g/d intake offered reasonable assurance that serum 25(OH)D concentrations in adults would be > 40 nmol/L, but did not ensure that most subjects would attain serum 25(OH)D concentrations considered desirable (> 75 nmol/L). The 100- g/d intake offered reasonable assurance that 25(OH)D concentrations
in adults would be > 69 nmol/L (Figures 1 and 2), close to the lower end of the desirable concentration.
If the serum 25(OH)D concentration is the appropriate measure of vitamin D nutritional adequacy (1), then more of the present type of specific data are needed to define the amounts of vitamin D required to ensure that for “practically all healthy persons” serum 25(OH)D concentrations are maintained above an
amount considered adequate. There are subgroups who require ≥25 g vitamin D/d to maintain acceptable 25(OH)D concentrations. Gloth et al (46) reported that in older patients with 25(OH)D concentrations < 25 nmol/L, vitamin D intakes ranged as high as 29 g/d. Patients with cystic fibrosis require > 20 g vitamin D/d to maintain 25(OH)D concentrations > 40 nmol/L (47). Despite the greater number of subjects and the longer follow-up in the present study than in previous comparable studies
(3, 18, 19), consumption of vitamin D3 at intakes ≥100 g/d causes no harm and effectively raises 25(OH)D to high-normal concentrations in practically all adults.
REFERENCES
1. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary reference intakes: calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy
Press, 1997.
2. National Research Council. Recommended dietary allowances. 10th ed. Washington, DC: National Academy Press, 1989:92–7.
3. Narang NK, Gupta RC, Jain MK, Aaronson K. Role of vitamin D in pulmonary tuberculosis. J Assoc Physicians India 1984;32:185–6.
4. Adams JS, Lee G. Gains in bone mineral density with resolution of vitamin D intoxication. Ann Intern Med 1997;127:203–6.
5. Marriott BM. Vitamin D supplementation: a word of caution. Ann Intern Med 1997;127:231–3.
6. Yates AA. Process and development of dietary reference intakes: basis, need, and application of recommended dietary allowances. Nutr Rev 1998;56:S5–9.
7. Gallagher JC, Kinyamu HK, Fowler SE, Dawson-Hughes B, Dalsky GP, Sherman SS. Calciotropic hormones and bone markers in the elderly. J Bone Miner Res 1998;13:475–82.
8. Harris SS, Dawson-Hughes B. Seasonal changes in plasma 25-hydroxyvitamin D concentrations of young American black and white women. Am J Clin Nutr 1998;67:1232–6.
9. Chapuy MC, Preziosi P, Maamer M, et al. Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 1997;7:439–43.
10. Liu BA, Gordon M, Labranche JM, Murray TM, Vieth R, Shear NH. Seasonal prevalence of vitamin D deficiency in institutionalized older adults. J Am Geriatr Soc 1997;45:598–603.
11. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med 1998;338:777–83.
12. Perry HM, Bernard M, Horowitz M, et al. The effect of aging on bone mineral metabolism and bone mass in Native American women. J Am Geriatr Soc 1998;46:1418–22.
13. Peacock M. Effects of calcium and vitamin D insufficiency on the skeleton. Osteoporos Int 1998;8(suppl):S45–51.
14. McKenna MJ, Freaney R. Secondary hyperparathyroidism in the elderly: means to defining hypovitaminosis D. Osteoporos Int 1998; 8(suppl):S3–6.
15. Heaney RP. Vitamin D: how much do we need, and how much is too much? Osteoporos Int 2000;11:553–5.
16. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69:842–56.
17. Arthur RS, Piraino B, Candib D, Cooperstein L, Chen T, West CPJ. Effect of low-dose calcitriol and calcium therapy on bone histomorphometry and urinary calcium excretion in osteopenic women.
Miner Electrolyte Metab 1990;16:385–90.
18. Tjellesen L, Hummer L, Christiansen C, Rodbro P. Serum concentration of vitamin D metabolites during treatment with vitamin D2 and D3 in normal premenopausal women. Bone Miner 1986;1:407–13.
19. Barger-Lux MJ, Heaney RP, Dowell S, Chen TC, Holick MF. Vitamin D and its major metabolites: serum levels after graded oral dosing in healthy men. Osteoporos Int 1998;8:222–30.
20. Trang H, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998;68:854–48.
21. Gokce C, Gokce O, Baydinc C, et al. Use of random urine samples to estimate total urinary calcium and phosphate excretion. Arch Intern Med 1991;151:1587–8.
22. Cleveland WS. Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc 1979;74:829–36.
23. Colton T. Regression and correlation. In: Colton T, ed. Statistics in medicine. Boston: Little Brown and Company, 1974:189–216.
24. Holick MF. Environmental factors that influence the cutaneous production of vitamin D. Am J Clin Nutr 1995;61(suppl):638S–45S.
25. McHenry CR, Rosen IB, Walfish PG, Pollard A. Oral calcium load test: diagnostic and physiologic implications in hyperparathyroidism. Surgery 1990;108:1026–31.
26. Guillemant J, Guillemant S. Effects on calcium and phosphate metabolism and on parathyroid function of acute administration of tricalcium phosphate. Bone 1991;12:383–6.
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Default Vitamin A Information

Who is usually deficient in Vitamin A?

http://www.who.int/nut/vad.htm
Vitamin A deficiency (VAD) is the leading cause of preventable blindness in children and raises the risk of disease and death from severe infections. In pregnant women VAD causes night blindness and may increase the risk of maternal mortality.

http://www.yourhealth.com.au/index....tent.php?id=153
Vitamin A

What is it and What Does it Do?

Vitamin A is a fat-soluble vitamin that helps cells reproduce normally - a process called differentiation. Cells that have not properly differentiated are more likely to undergo precancerous changes. Vitamin A, by maintaining healthy cell membranes and supporting immune function, helps prevent infection. It is also needed for the formation of bone, protein, and growth hormone. Vitamin A may be produced in the body from the conversion of beta-carotene. People who limit their consumption of liver, dairy foods, and beta-carotene-containing vegetables can develop a vitamin A deficiency. Extremely low birth weight babies (2.2 pounds or less) are at high risk of being born with a deficiency, which increases the risk of lung disease. The earliest deficiency sign is poor night vision, however other symptoms include dry skin, increased frequency of infections, and metaplasia (a precancerous condition).

Deficiencies are likely to occur with a variety of conditions causing malabsorption. A high incidence of vitamin A deficiency in people infected with the HIV virus has also been reported. People with hypothyroidism have impaired ability to convert beta-carotene to vitamin A. Deficiency during pregnancy can cause birth defects.

Dietary Sources
Liver, dairy, and cod liver oil contain significant amounts of vitamin A.

Therapeutic Uses
Recurrent infections of the mucous membranes, including bronchitis, thrush, urinary tract infections, conjunctivitis
• Support for poor immune function, including HIV
• Night blindness, retinopathy
• Cystic fibrosis
• Digestive disorders including chronic gastritis, peptic ulcer, coeliac disease and Crohn’s disease
• Iron-deficiency anaemia
• Acne, poor wound healing
• Abnormal pap smear
• Hypothyroidism

Common and Optimal Dosage Range
• RDI for adults is approximately 2,500 IU. Greater amounts are needed in certain illness and during breastfeeding. Therapeutic doses range from 10,000 to 500,000 IU per day with careful monitoring.
• Taking vitamin A and iron together helps overcome iron deficiency more effectively than iron supplementation alone.
Cautions, Contraindications and Side Effects
• Up to 25,000 IU (7,500 mcg) of vitamin A per day is considered safe for most adults.
• Women who are or could become pregnant should take less than 10,000 IU (3,000 mcg) per day of vitamin A to avoid the risk of birth defects. All supplements containing vitamin A will carry the warning that more than 2,500 IU may cause birth defects. The Teratology Society in the United States recommends a daily intake of 8000 IU for pregnant women, or a supplement for pregnant women who receive less than 2,200 iu daily, because deficiencies are also associated with birth defects and poor pregnancy outcomes.
• In rare cases, intake above 25,000 iu (7,500 mcg) per day can cause headaches, dry skin, hair loss, fatigue, bone problems, and liver damage. At higher levels (for example 100,000 IU per day) these problems become more common.
• Certain medications may interact with vitamin A. Please discuss the use of vitamin A and your current medication(s) with your healthcare practitioner.

Now to address the concern re vitamin A toxicity in conjunction with vitamin A.

It seems in both cases it is the synthetic forms of the vitamins that are toxic in large doses, not the natural ones. Gee , I guess the body can tell the difference between natural and synthetic vitamins after all!!! So much for those who say the body is too stupid!!

http://cerhr.niehs.nih.gov/genpub/t...min_a-ccae.html
Overview

Vitamin A is a chemical that is essential to sustain human life and must be provided in adequate amounts through food or other dietary supplements. However, excessive consumption of vitamin A can cause birth defects. Recently, birth defects have been observed in children born to mothers taking synthetic vitamin A drugs used to treat acne. These observations raised concerns that high vitamin A intake during pregnancy could cause birth defects in unborn children. Initial studies comparing levels of vitamin A intake during pregnancy in women who had healthy infants to woman who gave birth to infants with birth defects were contradictory. However, birth defects were observed in the young of animals fed high concentrations of vitamin A during pregnancy. The California Environmental Protection Agency (CAL/EPA) has identified retinol or retinyl esters (types of pre-formed vitamin A) as developmental toxins when administered at doses greater than 10,000 International Units (IU). The Food and Drug Administration has established a daily recommended allowance (RDA) of 5,000 IU for vitamin A. Because vitamin A is required to ensure reproductive health, it has been recommended that pregnant woman maintain their intake around 8,000 IU and that vitamin A be taken in the form of beta-carotene, which is not considered toxic. Women can take vitamin A in many forms. Pre-formed vitamin A (retinol or retinyl esters) is found in liver, vitamin tablets, and fortified cereals. Beta-carotene is found in fruits and vegetables and is converted to vitamin A in the body.

Description of Vitamin A

Vitamin A occurs in several different forms. Pre-formed vitamin A is a family of substances called retinol or retinyl esters (Teratology Society; 1987). Retinyl palmitate and retinyl acetate are examples of retinyl esters that are commonly used in vitamins (FDA Talk Paper; October 6, 1995). Pre-formed vitamin A is also found in animal products like liver and in fortified cereals and vitamin tablets (FDA Talk Paper; October 6, 1995). Beta-carotene, found in fruits and vegetables, is a vitamin A precursor, which means that it is converted to vitamin A in the body.

Concentrations of vitamin A are expressed in terms of International Units (IU) or retinol equivalents (RE) (Teratology Society; 1987). An IU is equivalent to 0.3 milligrams (mg) of a vitamin A compound called all-trans-retinol. Units of RE are used to standardize different forms of dietary vitamin A and 1 RE is equal to 1 mg of all-trans-retinol.

Vitamin A Toxicity During Pregnancy

Some women who used the synthetic vitamin A drug Accutane® while pregnant gave birth to babies with birth defects, according to the March of Dimes (March of Dimes 1999). Examples of birth defects were "hydrocephaly (enlargement of the fluid-filled spaces in the brain); microcephaly (small head); mental retardation; ear and eye abnormalities, cleft lip and palate, and other facial abnormalities and heart defects." Women who took the drug also had a higher risk of miscarriage. The active ingredient in Accutane®, isotretinoin, is produced in the body in small amounts after eating vitamin A. Therefore, concerns were raised that a high intake of vitamin A by pregnant women could cause birth defects in infants.

Contradictory results have been obtained in studies that examined vitamin A intake during pregnancy and birth defects in humans. A study sponsored by the National Institute of Child Health and Human Development (NICHD) compared vitamin A intake during pregnancy in women who had given birth to infants who were healthy, who had a neural tube defect (defects in the brain and spinal cord), and who had a cranial-neural-crest defect (malformation of cleft palate, face, or heart) (NIH News Alert; July 22, 1997). It was concluded, "When compared to women in the control group, neither the women in the neural tube defect group nor those in the group pregnant with children having other major malformations were found to have been more likely to have consumed between 8,000 and 10,000 IU of vitamin A."

A similar study conducted at the Boston University School of Medicine compared vitamin A intake during pregnancy in women who had given birth to healthy infants or who had cranial-neural-crest defects (defects of the head, face, nervous system excluding the neural tubes, thymus, and heart), neural tube defects (defects in brain or spinal cord), or defects of the bones, muscles, or urinary tract (New England Journal of Medicine Journal Club; 333:1369-73; 11/23/95). The study found that women who took about 10,000 IU or more vitamin A during pregnancy were more likely to give birth to a child with a cranial-neural-crest defect. It was estimated that intakes of greater than 10,000 IU of vitamin A by pregnant women could result in a defect in one of every 57 infants.

According to the Teratology Society, there are several reports of malformations in humans following a vitamin A intake of 25,000 IU/day or more during pregnancy (Teratology Society; 1987). Some of the defects were similar to those caused by isotretinoin.

Animal studies have demonstrated birth defects similar to those produced by Accutane®. Cleft palates and defects of the head, face, and eye were seen in the young of pregnant rats fed 35,000 IU of vitamin A (Teratology Society; 1987). Similar defects were also observed following vitamin A administration to pregnant mice, guinea pigs, hamsters, and rabbits.

Vitamin A Regulations and Recommendations

Retinol/retinyl esters (pre-formed vitamin A) in doses greater than 10,000 IU, or 3,000 retinol equivalents are listed on the CAL/EPA Proposition 65 list of developmental toxins (Cal/EPA Proposition 65 List). This means that an expert group of scientists found sufficient evidence that the compounds can be harmful to unborn children. The following statement is included with the listing, "NOTE: Retinol/retinyl esters are required and essential for maintenance of normal reproductive function. The recommended daily level during pregnancy is 8,000 IU".

Several recommendations have been made for vitamin A intake by pregnant women. The FDA has recommended that pregnant women obtain vitamin A in the form of beta-carotene whenever possible (FDA Talk Paper; October 6, 1995). According to the FDA, "beta-carotene is a substance found naturally in plants, and it can be converted to vitamin A in the body. It is considerably less toxic than the pre-formed vitamin A. Therefore, women of child-bearing age are advised to choose fortified foods that contain vitamin A in the form of beta-carotene rather than pre-formed vitamin A, whenever possible. The vitamin A in fruits and vegetables is naturally in the form of beta-carotene, and high intakes of vitamin A from these sources are generally not of concern. Taking too little vitamin A can result in adverse effects just as can taking in too much. The key is in finding the 'right amount' through carefully reading product nutrition labeling."

The following list contains recommendations from the Teratology Society (Teratology Society; 1987):

Supplementation of 8,000 IU vitamin A (as retinol/retinyl esters) per day should be considered the recommended maximum prior to or during pregnancy until further evaluations can be performed in the human population. It is important to determine the type of vitamin A consumed, since beta-carotene has not been associated with vitamin A toxicity in animals or man.

Manufacturers of vitamin A (as retinol or retinyl esters) should lower the maximum amount of vitamin A per unit dosage to 5,000-8,000 IU (1,500-2,400 RE) and identify the source of the vitamin A. High dosages of vitamin A as retinol/retinyl esters (25,000 IU or more) are not recommended.

Labeling of products containing vitamin A supplements (as retinol/retinyl esters) should indicate (a) that consumption of excessive amounts of vitamin A may be hazardous to the embryo/fetus when taken during pregnancy; and (b) that women of childbearing potential should consult with their physicians before consuming these products.

Dr. Larry Gilstrap of the American College of Obstetricians and Gynecologists was quoted as saying (USA Today), "We want to reassure women that the amount (of vitamin A) in their prenatal vitamin is safe, and so is the amount they're likely getting from their diet.'' Gilstrap went on to say that vitamins given to pregnant women usually contain 4,000-5,000 IU. Dr. Gilstrap considered this amount of vitamin A to be sufficient because it leaves room for dietary sources of vitamin A such as meat and dairy products.

G. Oakley and J. Erickson from the Centers for Disease Control and Prevention (CDC) stated that pregnant women should take supplements containing less than 8,000 IU vitamin A and limit the amount of liver they eat (New England Journal of Medicine Journal Club; 333:1369-73; 11/23/95).

Another study
http://www.biotech-info.net/disorders.html

Vitamin A Deficiency Disorders: Origins of the Problem and Approaches to Its Control"

Alfred Sommer, MD, MHS
Dean
The Johns Hopkins University
Bloomberg School of Public Health
2001

The announcement that Swiss scientists had genetically modified a strain of rice to produce beta-carotene, a precursor of vitamin A, set off heated debate between those who believe this would solve the global problem of vitamin A deficiency and those who argue that such genetically engineered products might do more harm than good. Neither extreme is tenable. If — and it remains a big “if” — “golden rice” and its variants prove safe and effective, they will be a valuable new tool for controlling vitamin A deficiency. Under the most optimistic of circumstances, however, they will never solve the global problem by themselves. This review attempts to place this new tool in perspective.

Vitamin A deficiency disorders encompass the full spectrum of clinical consequences associated with suboptimal vitamin A status.(1) These disorders are now known to include reduced immune competence resulting in increased morbidity and mortality (largely from increased severity of infectious diseases); night blindness, corneal ulcers, keratomalacia and related ocular signs and symptoms of xerophthalmia; exacerbation of anemia through suboptimal absorption and utilization of iron; and other conditions not yet fully identified or clarified (e.g., retardation of growth and development).(2)

Magnitude and Distribution

Clinical and sero-epidemiologic studies and surveys indicate that vitamin A deficiency is widespread throughout the developing world. Vitamin A deficiency has long been recognized in much of South and Southeast Asia (India, Bangladesh, Indonesia, Vietnam, Thailand, the Philippines) by the common presentation of clinical cases of xerophthalmia (night blindness to permanently blinding keratomalacia). Subsequent studies in Africa, where it had been less well recognized, indicated that a large proportion of pediatric blindness was due to acute deterioration in vitamin A status during measles and similar childhood infections.(3, 4)

Vitamin A deficiency was found to increase childhood morbidity and mortality(2, 5-10) in populations in which xerophthalmia was not readily recognized(11) and in greater numbers than would be expected solely from the increase in mortality associated with xerophthalmia.(2, 12) This discovery led to the recognition that seemingly mild biochemical deficiency, insufficient to cause xerophthalmia, accounts for large numbers of preventable childhood deaths.

The extent and distribution of vitamin A deficiency and its consequences are remarkably well established. Numerous local and national surveys have been conducted. In countries where they have not been conducted, data from nearby countries with similar characteristics (under-5-year mortality, poverty, diet) allow for judicious extrapolation. The few intensive national surveys linked to longitudinal studies(13) and extrapolations from sero-surveys and community-based randomized intervention trials show that vitamin A deficiency poses a significant problem in more than 70 countries.(14) Recent calculations suggest that roughly 150 million children are deficient: every year 10 million children develop xerophthalmia, 500,000 children are permanently blinded from xerophthalmia and 1 to 2 million children die unnecessarily.(15)

Vitamin A deficiency disorders have not been quantified in women of childbearing age. Older anecdotal reports(16, 17) and recent surveys(18, 19) indicate that night blindness from vitamin A deficiency is common among pregnant women in India, Indonesia, Bangladesh, Nepal and elsewhere, particularly during the latter half of pregnancy. Most surveys reveal rates of night blindness of 10% or more during pregnancy in populations in which the children are commonly deficient.(1) A recent large-scale randomized placebo-controlled trial of vitamin A or beta-carotene supplementation in Nepali women reduced maternal mortality by approximately 40%,(20, 21) an effect that persisted for at least one year postpartum.(22)

Vitamin A deficiency disorder affects large numbers of young children and women of childbearing age throughout the developing world. Current estimates do not include China, where recent visits with nutritionists and pediatricians in the southwestern regions identified cases of xerophthalmia and where a recent UNICEF survey revealed depressed serum retinol values and night blindness during pregnancy in large, impoverished regions.(23-25) The size of the global problem is therefore likely to grow as additional data are gathered.

Origins of Deficiency

Children begin life with an urgent need for vitamin A. Full-term infants — even those of well-nourished mothers in wealthy countries — are born with barely enough vitamin A to sustain them during the first few days of life. During the first six months of life they need at least 125 mg of retinol equivalents daily to prevent xerophthalmia and about 300 mg to thrive (and accumulate adequate liver stores of 20 mg per gram of liver).(1, 26, 27)

The only significant source of vitamin A for young infants is breast milk (or equivalent formulas). Except when mothers suffer from severe protein-energy malnutrition, the quantity of breast milk is roughly similar around the globe, but the concentration of vitamin A in that milk varies dramatically with the vitamin A status of the mother.(26, 28) When mothers are vitamin A deficient, breast milk concentrations will be low. Without supplemental vitamin A, their infants will become deficient.

Children in developing countries are at risk of consuming a vitamin A~deficient diet throughout life, not just during early infancy. Although Western populations receive abundant preformed vitamin A from animal products (eggs, butter, cheese, liver, processed foods fortified with vitamin A), poor rural populations in developing countries rely on beta-carotene, a precursor of vitamin A found in dark-green leafy vegetables, carrots and colored fruits (mango and papaya). Even when abundant, these are poor substitutes for animal sources of the preformed vitamin: many children do not like dark-green leafy vegetables; fruits are often costly, sold as a cash crop or highly seasonal (e.g., mangos); and many vegetables bind beta-carotene tightly to their cellular matrices, yielding little during digestion. Recent data indicate that the bioavailability (and bioconversion) of dark-green leafy vegetable sources of beta-carotene is much lower than previously supposed,(29, 30) with perhaps no more than 2% to 4% being absorbed, converted to vitamin A, and made available to meet metabolic needs.

Children in the developing world probably need more vitamin A than do their better nourished Western counterparts. Diarrhea, childhood exanthematous diseases and respiratory infections are more common in poor rural populations, further reducing vitamin A absorption (diarrhea) while increasing utilization (measles) and excretion (respiratory infection).

Why young children in developing countries are deficient in vitamin A is clear. Their greatest risk of becoming vitamin A deficient is during the first few years of life, when their diets are the least diverse, growth (hence need) is greatest and they are at highest risk of life-threatening infections. As they enter their school-age years these factors begin to moderate even though deficiency persists and mild manifestations (e.g., night blindness and Bitot’s spots) remain common.

Why women are so frequently deficient is less clear. They also have a similarly unvaried diet that is largely deficient in good sources of preformed vitamin A. Pregnancy and lactation place additional burdens on their meager vitamin A stores. Other consequences of pregnancy probably explain why deficiency is most severe — and night blindness most common — during the latter half of pregnancy. Even though pregnancy-related night blindness spontaneously disappears during the early postpartum period, the underlying deficiency does not. As a consequence these women suffer an increase in mortality for at least one year postpartum.(20-22)

Combating Vitamin A Deficiency

There is global agreement on the need to combat vitamin A deficiency.(2, 14) More than 70 countries have formal intervention programs, although only a few (Nepal, Indonesia, Tanzania, Bangladesh, Vietnam) have made significant, discernible progress. Three basic strategies exist for increasing vitamin A intake: increasing the consumption of foods rich in vitamin A and provitamin A; fortifying commonly consumed dietary items with vitamin A (or beta-carotene); and providing large, periodic, vitamin A supplements to high-risk populations.

Dietary Diversification

Many nutritionists consider increasing the consumption of natural dietary sources of vitamin A to be the logical long-range solution to deficiency. Despite occasional demonstration projects and correlational analyses,(31) little definitive evidence exists that vitamin A sufficiency can be achieved — let alone sustained — through traditional food sources, particularly those available to poor, rural, high-risk populations. As noted, vegetables are poor sources of provitamin A beta-carotene. Although they contain considerable quantities of beta-carotene, these are not readily bioavailable. It needs to be shown that vulnerable children can consume quantities of dark-green leafy vegetables sufficient to normalize their vitamin A status.

Adults may be able to obtain sufficient vitamin A by consuming far larger amounts of vegetables and fruits than children consume or through the greater diversity of their diet, but this too needs documentation. In at least two studies, women provided daily with large helpings of dark-green leafy vegetables failed to significantly improve their vitamin A status(29, 32) in contrast to those fed cookies containing pure synthetic (therefore readily absorbed) beta-carotene.(29) Introducing animal sources of preformed vitamin A (e.g., eggs) into the diet might make a significant difference but remains beyond the resources (and cultural patterns) of many of the populations at highest risk.

Fortification by Conventional Means

Fortifying dietary items with preformed vitamin A or beta-carotene is a proven strategy for preventing deficiency.(33) In the early 1900s Denmark legislated vitamin A fortification of margarine because its growing dairy exports deprived the poorer classes of once-abundant butter, for which they initially substituted vegetable oil~based margarine, which is naturally devoid of vitamin A. In the United States, Western Europe and most wealthy countries, a wide variety of dietary items is fortified with vitamin A (milk, margarine, cereal products). Developing countries have experimented with fortifying a range of products with vitamin A (monosodium glutamate, wheat, noodles, sugar). To date, only sugar fortification, primarily in Latin America, has taken hold.(34)

Traditional fortification techniques require a dietary item that is consumed in suitable quantities by the groups at highest risk; is processed at a limited number of sites where the fortificant can be conveniently added; stabilizes vitamin A during its normal shelf life in the marketplace (vitamin A is unstable in salt, making salt unsuitable for vitamin A but fine for delivering iodine); results in little increase in cost to the consumer; and has acceptable organoleptic qualities (color, smell, taste). These requirements have been difficult to achieve for high-risk poor populations that generally consume a monotonous diet devoid of expensive, centrally processed items.

Fortification by Genetic Modification

In an attempt to overcome some of the obstacles facing conventional fortification, scientists have begun to genetically modify traditional dietary items to produce beta-carotene. Monsanto produced rape seed and mustard rich in beta-carotene and, more recently, scientists funded by the Rockefeller Foundation produced a strain of rice — golden rice — genetically modified to produce beta-carotene.(35) This may well herald an important strategy for controlling vitamin A deficiency, particularly because rice is the dietary staple of many of the most-deficient populations.

Some hurdles need to be surmounted before golden rice or its variants can have an effect. The strains must be able to grow under the varied conditions in countries with vitamin A~deficient populations. The yield and the cost must be attractive to the farmer (or benefit from public sector subsidization). The organoleptic qualities of the rice must be acceptable to the target population (women and children). The beta-carotene needs to be bioavailable, the degree dependent on its concentration in the rice, the matrices to which it is bound, the effect of traditional cooking methods and the amount consumed.

Although genetically modified rice could go a long way toward controlling vitamin A deficiency, it will never completely solve the problem. Many deficient populations do not consume rice, and even within traditional rice-consuming countries, some high-risk groups will not be able to afford it.

Supplementation

Vitamin A (retinol) supplements — naturally occurring (as in cod liver oil) or synthetically derived (multivitamin preparations) — have long been used to prevent vitamin A deficiency and its associated disorders.(2, 36) Vitamin A is a component of prenatal and infant multivitamins routinely consumed by Western populations. Periodic administration of large doses of vitamin A to children was pioneered in India(37) and advanced globally after the first major international meeting on the control of vitamin A deficiency in 1974.(32)

Periodic supplementation is the most widely implemented intervention for controlling vitamin A deficiency in the developing world. Countries have found these programs to be relatively easy and quick to initiate at relatively modest marginal cost.(2, 38) Supplements are extremely inexpensive, at 2 to 4 cents per dose of 200,000 international units (IU). Most of the cost is for the gelatin capsule; the cost for the vitamin A is less than 1 cent.

The major cost for (and impediment to) population-wide supplementation is the delivery system. Recommendations called for the administration of 200,000 IU every 4 to 6 months to all children 12 to 60 months of age. Unfortunately, that often requires a delivery mechanism such as that presently used successfully in a number of countries (e.g., Nepal and Bangladesh). In Nepal, 37,000 village women volunteers reach more than 2 million children during special “Vitamin A Days” held twice every year.(39)

To better use existing delivery channels, many countries have piggybacked vitamin A distribution onto regular immunization efforts. In particular, 25,000 or 50,000 IU of vitamin A is given to young children at ages 6, 10, and 14 weeks when they receive their diptheria, pertussis and tetanus immunizations. A fourth dose (100,000 IU) is administered at age 9 months with measles immunization.(40) The rationale for this schedule is that an existing distribution mechanism is available, minimizing the marginal cost of delivery; a high risk of deficiency exists during the first year of life (200,000 IU is given to mothers 6 to 8 weeks postpartum to boost breast milk vitamin A concentration); and infants are at greatest risk for the consequences of deficiency, particularly mortality. Coverage achieved by supplement distribution programs has dramatically risen in the past two years, largely because vitamin A administration was included in national immunization days, which were designed to deliver polio vaccine. More than 40 countries reported covering more than 80% of their target children with vitamin A supplements during 1998.(1, 41)

Although randomized controlled clinical trials have demonstrated the value of periodic supplementation,(2) in practice it has proved difficult to reach children after the first year of life; indeed, with immunization rates falling below expected targets, these too have not met their goals. To compound the problem, national immunization days will soon be phased out.

A recent multinational trial sponsored by the World Health Organization (WHO) suggests that the present regimen of dosing mothers with 200,000 IU postpartum and their children three times in the first 14 weeks of life with 25,000 IU does not improve vitamin A status much beyond age 6 months.(42) In response, a recent informal consultation organized by WHO recommended that doses to infants and mothers be increased: 400,000 IU to postpartum women (in two doses during the preconceptual period) and 50,000 IU to infants at least three times before age 6 months. Although the effect of these increases is yet to be ascertained, evidence suggests they will be safe and effective.(27)

Safety Considerations

Undue concern over vitamin A toxicity, a rare and transient condition,(43) has complicated the design of intervention strategies and unnecessarily diverted attention and commitment from effective control strategies. Because safety relates to the prevention of deficiency, only two issues arise: teratogenicity and acute toxicity.

Very large doses of vitamin A during the first trimester of pregnancy can be teratogenic, so high-dose supplementation of women of childbearing age is only recommended during the infertile postpartum period.(40) Acute toxicity, although harmless and transient, can result in nausea and vomiting. If mothers notice and are concerned, it might result in lower compliance rates, so supplement size is adjusted for the child’s age. Even so, young children who might inadvertently receive multiples of the recommended dose (in addition to increased amounts in breast milk) will not suffer significant, permanent sequelae.(1) The implications for intervention strategies are minimal.

Diet

Traditional foods cannot produce teratogenic or toxic effects. For deficient populations the primary source of vitamin A is vegetables, which lack the preformed vitamin. Ingesting large quantities of carrots and other carotenoid-rich vegetables may produce high carotene levels, but these are harmless. Because the body regulates conversion of beta-carotene to vitamin A, serum retinol does not rise to toxic levels.

Fortification

Programs that add retinyl palmitate (preformed vitamin A) to dietary items carefully adjust the level of fortification to benefit consumers whose diets are most deficient without exposing wealthier segments of society, whose diets might be richer in preformed vitamin A, from consuming excessive amounts. These programs take pains to achieve a balance that best serves both groups. The choice of vehicle can optimize this relationship.

Fortifying a product or a specific package of that product (e.g., the smallest packets of monosodium glutamate) uniquely ingested by those who are most deficient increases the amount of vitamin A that can be safely added. Nonetheless, ongoing surveillance is valuable in identifying isolated groups or individuals who purposely purchase and consume large doses of supplements on a sustained basis.

Fortification through genetic modification poses no risks of vitamin A toxicity. Genetically modified crops (e.g., golden rice, enriched canola oil) produce beta-carotene, not preformed vitamin A.

Supplementation

This intervention is potentially the most problematic because it is theoretically possible to overdose the recipient through frequent, inadvertent dosing. From a practical standpoint, however, serious or sustained side effects require very high, frequent and persistent dosing (50,000 to 100,000 IU daily for 3 to 6 months).(1, 27, 40, 43) An often expressed concern is that a child might receive three or even four high-dose supplements within a month (a regular distribution, a dose during measles, plus a third or fourth from an overly zealous local health worker). The worst result, however, would be a day or two of nausea and vomiting. This risk pales in comparison with the millions of children who would otherwise die or be blinded.

Conclusions

A decade ago the public health and nutrition communities recognized the need to improve the vitamin A status of young children throughout the developing world.(44) The World Bank has estimated that vitamin A supplementation (the only approach they modeled) was among the most cost-effective health interventions available, at less than US$1 per disability-adjusted life year.(45) Although more than 70 countries have embraced the global goal of eliminating vitamin A deficiency as a public health problem, progress has been slow, largely because of the costs and logistical challenges to changing behavior (diets), delivering large-dose supplements regularly, and fortifying traditional dietary items. A number of bilateral and international agencies recently recommitted themselves to these efforts, even as continuing research expands the implications of deficiency. New tools, such as genetically modified staple crops, could provide important strategies and stimulate these global efforts.

References


Report of the XX IVACG Meeting, Hanoi, February, 2000. ILSI Press: Washington, DC (in preparation).
Sommer A, West KP. Vitamin A Deficiency. Oxford: Oxford University Press, 1996.
Chirambo MC, BenEzra D. Causes of blindness among students in blind school institutions in a developing country. Br J Ophthalmol 1976;60:665-668.
Foster A, Sommer A. Childhood blindness from corneal ulceration in Africa: causes, prevention, and treatment. Bull WHO 1986;64:619-623.
Sommer A, Hussaini G, Tarwotjo I, Susanto D. Increased mortality in children with mild vitamin A deficiency. Lancet 1983;2:585-588.
Sommer A, Tarwotjo I, Djunaedi E, West KP, Loeden AA, Tilden R, Mele L, Aceh Study Group. Impact of vitamin A supplementation on childhood mortality. A randomized controlled community trial. Lancet 1986;1:1169-1173.
West KP, Pokhrel RP, Katz J, LeClerq SC, Khatry SK, Shrestha SR, Pradhan EK, Tielsch JM, Pandey MR, Sommer A. Efficacy of vitamin A in reducing preschool child mortality in Nepal. Lancet 1991;338:67-71.
Rahmathullah L, Underwood BA, Thulasiraj RD, Milton RC, Ramaswamy K, Rahmathullah R, Babu G. Reduced mortality among children in Southern India receiving a small weekly dose of vitamin A. N Engl J Med 1990;323:929-935
Muhilal, Permeisih D, Idjradinata YR, Muherdiyantiningsih, Karyadi D. Vitamin A-fortified monosodium glutamate and health, growth, and survival of children: a controlled field trial. Am J Clin Nutr 1988;48:1271-1276.
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Ghana VAST Study Team. Vitamin A supplementation in northern Ghana: effects on clinic attendances, hospital admissions, and child mortality. Lancet 1993;342:7-12.
Sommer A. Clinical research and the human condition: moving from observation to practice. Nat Med 1997;10:1061-1063.
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Grant JP. The State of the World’s Children. Oxford: Oxford University Press, 1995.
Humphrey JH, West KP, Sommer A. Vitamin A deficiency and attributable mortality among under-5-year-olds. Bull WHO 1992;70:225-232.
Sommer A. Nutritional Blindness: Xerophthalmia and Keratomalacia. Oxford: Oxford University Press, 1982.
Dixit DT. Night-blindness in third trimester of pregnancy. Indian J Med Res 1966;54:791-795.
Katz J, Khatry SK, West KP, Humphrey JH, LeClerq SC, Pradhan EK, Pokhrel RP, Sommer A. Night blindness during pregnancy and lactation in rural Nepal. J Nutr 1995;125:2122-2127.
Christian P, West KP, Khatry SK, Katz J, Shrestha SR, Pradhan EK, LeClerq SC, Pokhrel RP. Night blindness of pregnancy in rural Nepal - nutritional and health risks. Int J Epidemiol 1998;27:231-237.
West KP, Katz J, Khatry SK, LeClerq SC, Pradhan EK, Shrestha SR, Connor PB, Dali SM, Christian P, Pokhrel RP, Sommer A. Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group. BMJ 1999;318:570-575.
Christian P, West KP, Khatry SK, Kimbrough-Pradhan E, LeClerq SC, Katz J, Shrestha SR, Dali SM, Sommer A. Night blindness during pregnancy and subsequent mortality among women in Nepal: effects of vitamin A and beta-carotene supplementation. Am J Epidemiol 2000;152:542-547.
Pradhan L, the NNIPS Study Team. Reduction in maternal mortality associated with vitamin A supplementation extends beyond perinatal period (in preparation).
Sommer A. Personal observations in Sichuan Province, October 1998.
Yip R. Personal communication, September 2000.
Fei L. A Review of vitamin A deficiency research in minority areas of southwest China, 1996.
Humphrey J, Rice AL. Vitamin A supplementation of young infants. Lancet 2000;356:422-424.
World Health Organization. Report of an Informal Consultation on Vitamin A Supplementation. Yverdon-les-Bains, Switzerland. March 1-3, 2000. Geneva: World Health Organization.
Stoltzfus RJ, Hakimi M, Miller KW, Rasmussen KM, Dawiesah S, Habicht J, Dibley MJ. High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant. J Nutr 1993;123:666-675.
de Pee S, West CE, Muhilal, Karyadi D, Hautvast JGAJ. Lack of improvement in vitamin A status with increased consumption of dark-green leafy vegetables. Lancet 1995;346:75-81.
de Pee S, West CE, Permaesih D, Martuti S, Muhilal, Hautvast JGAJ. Orange fruit is more effective than are dark-green, leafy vegetables in increasing serum concentrations of retinol and _-carotene in schoolchildren in Indonesia. Am J Clin Nutr 1998;68:1058-1067.
Islam N, Talukder A, Tabibul AK, Bloem MW. Home gardening to scale: preliminary results from a nationwide program in Bangladesh. Report of the XVI IVACG Meeting, Chiang Rai, Thailand. Washington, DC: ILSI Press, 1994.
World Health Organization, U.S. Agency for International Development. Vitamin A deficiency and xerophthalmia. Report of a joint WHO/USAID Meeting. WHO Technical Report Series 590. Geneva: World Health Organization, 1976.
Blegvad O. Xerophthalmia, keratomalacia and xerosis conjunctivae. Am J Ophthalmol 1924;7:89-117.
Phillips M, Sanghvi T, Suarez R, McKigney J, Vargas V, Wickham C. The costs and effectiveness of three vitamin A interventions in Guatemala. Latin America and Caribbean Health and Nutrition Sustainability: Technical Support for Policy, Financing and Management. Washington, DC: International Science and Technology Institute Inc., 1994.
Ye X, Al-Babili S, Klöti A, Zhang J, Lucca P, Beyer P, Potrykus I. Engineering the provitamin A (_-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm. Science 2000;287:303-305.
Snell S. On nyctalopia with peculiar appearances on the conjunctiva. Trans Ophthalmol Soc UK 1880/81;1:207-215.
Swaminathan MC, Susheela TP, Thimmayamma BVS. Field prophylactic trial with a single annual oral massive dose of vitamin A. Am J Clin Nutr 1970;23:119-122.
West KP, Sommer A. Delivery of Oral Doses of Vitamin A to Prevent Vitamin A Deficiency and Nutritional Blindness. A State-of-the-Art Review. Rome, Italy: United Nations Administrative Committee on Coordination-Subcommittee on Nutrition, 1987.
Nepali Technical Assistance Group. When a vitamin A supplementation program turns into a long-term strategy. Kathmandu, Nepal, July, 2000
WHO/UNICEF/IVACG Task Force. Vitamin A Supplements: a Guide to Their Use in the Treatment and Prevention of Vitamin A Deficiency and Xerophthalmia. 2nd ed. Geneva: World Health Organization, 1997.
Schultink W. Personal communication, March 2, 2000.
WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group. Randomised trial to assess benefits and safety of vitamin A supplementation linked to immunisation in early infancy. Lancet 1998;352:1257-1263.
Bauernfeind JC. The Safe Use of Vitamin A. A Report of the International Vitamin A Consultative Group (IVACG). Washington, DC: Nutrition Foundation, 1980:1-44.
Sommer A. Vitamin A deficiency and childhood mortality (editorial). Lancet 1992;339:864.
World Bank. The World Bank World Development Report 1993: Investing in Health. Oxford University Press 1993

And...

http://members.iinet.net.au/~warpf/vitamina.html

What are the results of the vitamin A treatment study?

A six-year study of 600 patients with typical Retinitis Pigmentosa (RP) concluded that, on average, the course of retinal degeneration was slowed among patients receiving a specified daily vitamin A palmitate supplement. There was almost a 20% slower annual decline of remaining retinal function in the study patients who took 15,000 IU vitamin A palmitate compared to those who took only trace amounts, as monitored by electroretinographic (ERG) amplitudes (8.3% compared to 10.0%). The results also suggested that the course of disease might be faster on average among patients receiving a daily high dose supplement of vitamin E (400 IU) than among those receiving a trace dose of vitamin E. Based on the results of this study, it is recommended that most adult patients with the common forms of RP take a daily 15,000 IU supplement of vitamin A palmitate under the supervision of an ophthalmologist, and avoid the use of high dose supplements of vitamin E, such as 400 IU. TOP

Is this a cure?

Unfortunately, no. But it may be a help for many. This treatment may decrease the yearly loss of retinal function, but will not stop it. Adults who use this treatment may have on average slower annual decline of remaining retinal function than those not using this treatment. While this does not represent a cure, it does represent a first step in managing typical RP. The patient must not expect improved vision from one year to the next, nor expect that vision loss would be completely arrested. Research aimed toward the development of additional treatments, cure and prevention actively continues. TOP

What types of RP may be helped by this treatment?

The clinical treatment trial of vitamin supplementation included patients with typical forms of RP, including the common inheritance types of X-linked, autosomal dominant, and autosomal recessive, as well as isolated RP and Usher syndrome type 11. Several other less common forms of RP were not included because too few patients were available for the study. Also, there was no preliminary evidence to suggest that vitamins could modify the course of these forms. Usher syndrome type 1, atypical RP (for example, cone-rod dystrophy and unilateral RP), Bardet-Biedl syndrome, Lebers congenital amaurosis, Refsum disease and other less common syndromes that involve RP were not included. Also, patients were not evaluated in this study if they had very advanced RP; if they were below the fifth percentile of normal for body weight for their age, sex and height, if they had impaired liver function; or if they were under age 18. Therefore, based on this study, formal recommendation of vitamin A supplementation cannot be made for these groups of patients. They should be assessed individually by their doctors. TOP

Was any type of macular degeneration included in this study?

No. This study was limited only to typical RP. Macular degeneration, whether the juvenile onset or late onset, age-related form, was not included in this trial. In fact, because macular degeneration has different symptoms, it also might be caused by different disease processes than RP. Recommendations regarding vitamin supplementation for patients with macular degeneration will have to await completion of other studies now being conducted through projects supported by the US government. TOP

Can children who have RP be given supplements of vitamin A?

This is a very difficult question to answer. Because patients under the age of 18 were not evaluated in this study, no formal recommendation can be made. However, it seems reasonable for children with RP to be assessed individually by their ophthalmologist and paediatrician for possible vitamin A treatment with a dose that takes into account the age, weight, general health status, and published guidelines for the safe use of vitamin A. Your child’s doctor might consider use of a standard children’s multiple vitamin capsule containing 5,000 IU vitamin A and 30 IU vitamin E, among other components. The 15,000 IU daily supplement of vitamin A recommended for adults is well above a child’s recommended daily allowance. Refer below to questions 6 and 7 for a discussion of the potential adverse side effects from high intake of vitamin A. TOP

What are the possible side effects of taking too much vitamin A?

For normal healthy adults the US Recommended Daily Allowance (US RDA) of vitamin A is 5,000 IU. The RDA for children depends on age and weight, and ranges from 1400 IU for an infant to 3300 for a ten year old weighing 60 pounds. The designation "IU" stands for International Unit. It is based on a standardised level of activity and defines the amount of activity of the specific substance present in the capsule. Based on the study results, the daily dose recommended for most adult patients with RP is 15,000 IU from capsule supplements of vitamin A palmitate, in addition to a regular balanced diet, which typically provides 3,000-4,000 IU per day. This totals approximately 18,000 IU per day of vitamin A. Regular long-term intake of 25,000 IU or more daily as a supplement has been associated with liver damage and with birth defects if taken during pregnancy. Other side effects sometimes caused by very high doses include throbbing headache, appetite loss, weight loss, nausea, vomiting, dry skin, hair loss, fatigue and ankle swelling, among others. TOP

Is it safe to take 15,000 IU of vitamin A for many years?

There is not much information available now about the possible adverse effects of taking supplemental vitamin A for many years, even decades. However, no evidence of systemic illness or toxicity attributable to the daily intake of vitamin A palmitate capsules (15,000 IU) could be established during the six-year study based on blood tests, urinalyses, patient responses to a symptom questionnaire, and, in some cases, examination by a consulting internist. Nevertheless, it is extremely important that your own condition be monitored by a physician on a regular basis while you are taking vitamin A for extended time periods that will probably exceed the six-year term of this study. Development of side effects, including liver disease, cannot be excluded. Therefore, patients should have a yearly evaluation by their doctor while taking vitamin A supplements. TOP

Tell me more about this study on vitamin A. Why was it done?

This study was a prospective, double-masked clinical trial. Neither patient nor clinician knew to which treatment group the patient had been assigned. It was designed to assess the effectiveness of vitamin A and E supplements in halting or slowing the progression of RP. An independent Data Safety and Monitoring Committee provided advice to the investigators and monitored the accumulating data on a regular basis for evidence of harm or benefit to study participants. A total of 600 patients affected with typical RP from across the United States and Canada were enrolled in the study. All were in good general health, between the ages of 18 and 49, and entered the study with different initial levels of retinal function. TOP

Following an examination, participants were assigned randomly to one of four treatment groups:

15,000 IU vitamin A plus 3 IU vitamin E

75 IU vitamin A plus 3 IU vitamin E

15,000 IU vitamin A plus 400 IU vitamin E

75 IU vitamin A plus 400 IU vitamin E

Where can I get a copy of the full report on this study?

The report from this clinical treatment trial was published in the June 1993 issue of the scientific journal Archives of Ophthalmology, pages 761-772. You and your doctor should refer to this article and the accompanying editorial for a complete presentation and discussion of the results. This journal is available through medical school and university libraries. Your local library may be able to obtain a copy of the article for you. The RP Foundation is not able to provide copies of this report. TOP

Do the results of this study imply that vitamin A deficiency or an excess of vitamin E was the cause of my RP?

There is no clue now that isolated cases have been caused by vitamin imbalance. In fact, vitamin A and E levels present in the blood of unaffected and affected individuals do not differ significantly. Scientists have discovered that the actual cause of most typical RP is a mutation in one of several important genes, which then produces a defective protein. This explanation of the cause is borne out by the inheritance of RP as a genetic disease and by the discovery of the actual disease gene mutations in a large percentage of RP cases. It is possible that non-genetic causes for isolated cases of RP may be discovered in the future. TOP

What is vitamin A?

Vitamins are relatively complex organic substances that are not made by the human body. They are required in small amounts from a balanced diet in order to sustain normal metabolism and good health. Diseases caused by extreme vitamin deficiency can usually be cured when the lacking vitamin is supplied.

The vitamin A family includes all naturally occurring compounds with the biological activity of retinol. It occurs in precursor form (for example, beta-carotene) or preformed principally in animal fats including dairy products, fish liver oils and some yellow and dark-green vegetables. Vitamin A is essential for normal growth and development. Extremely severe nutritional deficiency of vitamin A can cause disease, including degeneration of mucous membranes (especially of the eye) and some other eye disorders. There are several members of the vitamin a family that have different functions in the body and therefore cannot be used interchangeably as a therapy. The preformed palmitate form of vitamin A is one member of this family, and is the recommended form for this treatment. In well-nourished individuals without a specific need for increased vitamin A, sufficient amounts are obtained from a regular balanced diet. Most of the body’s reserve of vitamin A is stored in the liver and abnormally high stored amounts can be toxic. TOP

How does supplemental vitamin A palmitate preserve retinal function for RP patients?

We don’t know. One well-defined function of vitamin A is in vision. It is intimately involved in the cascade of events triggered by light reaching the retina. A second major role of vitamin A is to keep cells healthy. A characteristic of RP is death of the specific, light-sensing cells in the retina, the photoreceptor cells called rods and cones. It is reasonable to hypothesise that high levels of vitamin A preserve these dying cells in some way. It is also possible that RP reduces the capacity of the retina to retain vitamin A. Likewise, RP cells may have an abnormal carrier protein causing vitamin A to be transported from the blood to the retina with lower efficiency. Whatever the explanation, it appears that vitamin A supplements may provide partial protection against loss of retinal call function as monitored by the ERG. TOP

Why should I avoid taking high dose supplements of vitamin E?

On average, study patients who took a daily supplement of 400 IU vitamin E with very low intake of vitamin A appeared to experience almost a 20% faster annual rate of decline of remaining retinal function than those who received only a trace amount of vitamin E (11.8% compared to 10.0%). Said another way, on average, a patient taking 400 IU of vitamin E might lose retinal function several years sooner. According to the study, if vitamin E supplements without vitamin A were started by the average patient at age 32, legal blindness could be accelerated by as much as five years. However, the study showed no evidence that normal dietary or small supplemental amounts of vitamin E have any adverse effect on RP. TOP

How could vitamin E cause an adverse effect on RP?

It is possible that taking frequent high doses of vitamin E might affect the course of RP at least in part by inhibiting the absorption or transport of vitamin A in the retina. In the study, it was observed that patients receiving 400 IU vitamin E had slight but significant decreases in vitamin A levels in their blood compared with those not receiving that dose of vitamin E. TOP

What if my doctor has advised me to take vitamin E for other reasons?

There is some early information from nutritional studies suggesting that supplemental vitamin E could be helpful in preventing heart disease. If your doctor has advised you to take vitamin E for any reason, you should ask to discuss the relative benefits and risks of taking vitamin E, or taking vitamin E along with vitamin A, given your general health and your eye disease. It is important to note that in the study vitamin A and E taken together did not appear to be as effective as vitamin A alone. TOP

To what extent might my vision be helped?

We can’t give you an answer that will predict your specific outcome. There are considerable differences in the severity of the disease among individuals at the same age, even within the same family. This study pooled the information from 600 patients and conclusions were based on "group averages". Actually, there are probably very few patients who exactly fit the "average" description. Some will have better vision and some will have worse vision than an average study patient. It isn’t possible to tell you the exact extent of benefit you will receive from this treatment. Some patients may not be helped at all, some may be helped more than others. Assurance cannot be given that a specific patient will benefit from this treatment. TOP

OK....what is the benefit of vitamin A for the "average" individual who has RP or Usher syndrome type 11?

In this clinical treatment trial, patients were examined annually for four to six years. Their retinal function was assessed by an ERG (electroretinogram). Those who took daily vitamin A palmitate supplements of 15,000 IU had almost a 20% slower loss of remaining retinal function each year than others in the study. Said another way, the average patient taking vitamin a could expect to keep retinal function for several years longer. If vitamin A supplements were started by the average patient at age 32, legal blindness could be delayed by as much as seven years. However, researchers cannot provide assurance that every patient will benefit from vitamin A treatment. TOP

But what does that say about me?

The best we can answer is that you may benefit from vitamin A treatment. It will be hard to tell by actual measurement, because this treatment slows the rate of degenerative process, but does not stop it. Complete blindness might be prevented in some people. Others might not be helped at all. TOP

Will I notice any change in my vision when I take vitamin A?

It is very unlikely that you will notice an improvement in your vision compared to any time in the past. The degenerative process will continue, although at a slower rate. Based on the results of this study, it is predicted that patients taking vitamin A over the long-term would have a higher probability of retaining the capacity to perform certain daily activities at a given age than patients not taking the vitamin A treatment. TOP

If I take vitamin A long enough, or start taking vitamin A as a young adult, will I be cured?

Vitamin a supplementation is not a cure for RP. "Cure" implies that health has been restored to normal, an a cure for RP would imply restoration of lost vision. Vitamin A supplementation has the potential to slow the disease course, therefore it is expected that supplementation begun in early adulthood may be more beneficial in the long-term than if begun later. For some patients, that might result in some amount of retained central vision for life. Since this study followed patients for four to six years, the benefits of longer term vitamin A supplementation will only be learned by following patients on this treatment throughout their lifetimes. TOP

Should I take vitamin A if I am already legally blind?

More than 50% of patients in the study were legally blind (defined as best corrected visual acuity of 20/200 or less or a central visual field diameter of 20 degrees or less in both eyes). However, as stated above, this study did not evaluate patients who were legally blind if they had very advanced RP because ongoing measurements of change in retinal function would have been difficult to assess. If you now have very advanced RP, you should consult with your ophthalmologist to get advice about the possible benefit of vitamin A for you. Other approaches being studied now may be helpful in the future for this group of patients. TOP

What should I do if I become pregnant or plan to become pregnant?

During your regular visits to your doctor, you should discuss the impact of vitamin A treatment on childbearing. You might be advised to stop taking vitamin A during periods leading up to planned pregnancies because of the potential for birth defects. Women who become pregnant should be advised to discontinue this dose of vitamin A during the entire pregnancy and during the period of breast feeding. However, you should continue to take prenatal vitamins as prescribed by your obstetrician. TOP

What should I do to begin vitamin A treatment?

This is a serious undertaking. First consult with an ophthalmologist, a medical doctor who specialises in eye care. Do no start taking vitamin A supplements on your own. Your ophthalmologist will want to do initial and subsequent annual evaluations, including tests to measure your blood level of vitamin A and to assess liver function. If these tests show that you have a pre-existing liver disease or abnormally high blood levels of vitamin A, your doctor may need to decrease your vitamin A intake accordingly. If you are not going to an ophthalmologist now, we suggest that you seek one out who is willing to advise you regarding your eye care. TOP

How can I find a doctor who is familiar with RP?

The WARP Foundation can give you a choice of ophthalmologists who specialise in retinal degenerative diseases. Please be aware that the Foundation is not an accrediting agency and has not screened those listed to judge their training, experience or standing in the medical community and cannot recommend one ophthalmologist in preference to another. Also, the Foundation cannot be held responsible for any services given by referral specialists or for the fees which they may charge. In conjunction with this list, you may wish to consult with your general practitioner or optometrist for their recommendation. TOP

How often will I need to be examined while taking vitamin A?

It would be a good practice to visit your ophthalmologist annually. Because liver disease is a potential side effect from long-term high dose vitamin A supplementation, blood tests to reassess liver function could be done at that time. Some ophthalmologists may want to measure annually the vision of their patients with RP, using tests to follow visual acuity, visual field and retinal function, like the ERG. TOP

Will my health insurance pay for annual appointments and tests?

You will need to check with your individual heath insurance carrier. Coverage of costs will depend on the individual insurance plan being used. You will need to look into this yourself. TOP

What do I need to know in order to buy the right capsules of vitamin A?

When you look for such a supplement, labels should be read very carefully to be sure the capsules contain vitamin A in the palmitate form, and not another component, especially beta-carotene. Beta-carotene is a natural precursor of the active form of vitamin A and in this instance is not a suitable substitute. Very high levels of beta-carotene are needed to achieve activity equivalent to 15,000 IU of vitamin A palmitate. The final activity could vary from person to person because people metabolise beta-carotene with different efficiencies. Therefore it is not a predictable source of the vitamin. Vitamin A in the palmitate form was used in this clinical treatment trial and the recommendations derived from the study apply specifically to this form. TOP

Where can I obtain capsules of 15,000 IU vitamin A palmitate?

At present, and to the best of our knowledge, vitamin A palmitate is available from most chemists and health food shops under the brand name "Nature’s Own" product number 203 but only in 5,000 IU capsules for approximately $6.00 for 100 capsules. To make up the correct dosage of 15,000 IU three capsules of 5,000 IU should be taken at one time. TOP

Do I need a prescription to get vitamin A supplements?

No. Vitamin A is classified as a food supplement and can be sold without a prescription. However, even though it is not a drug and a prescription is not required, vitamin A supplements potentially can cause side effects and should not be used for long periods without regular follow-up examinations by your ophthalmologist and/or physician. You should be sure to inform each doctor you see that you are taking supplements of vitamin A on a regular long-term basis because there may be instances where vitamin A sue could be contraindicated. TOP

When should I take the capsules and how should I store them

You might find it useful to develop a routine of taking the capsules each day right after breakfast. These vitamin A capsules have more than a one-year shelf life. You could purchase a full year supply (eleven bottles of 100 each) and store them at room temperature. TOP

Can I adjust my daily dose so that I can make use of lower or higher dosages that are sold at my local store?

In the study, optimal benefit occurred among patients with a total daily intake of 15,000 IU of vitamin A palmitate in capsule form and 3,000 IU vitamin A from diet. Lower intake gave less benefit and higher intake up to 25,000 IU provided no greater benefit. Toxic side effects have been associated with long-term intake of 25,000 IU and therefore, intake of below 15,000 IU and over should be avoided. Remember, more vitamin A than the dose recommended by this study is not better. Moreover, daily vitamin A intake exceeding 25,000 IU over the long-term may be toxic in adults and may cause side effects such as liver disease. TOP

Why can’t I simply take three "one-a-day" multiple vitamin capsules each day? Wouldn’t I get the right dosage of vitamin A by doing that?

In addition to 5,000 IU vitamin A, one-a-day multiple vitamin capsules contain other vitamins and components at 100% of the RDA (recommended daily allowance). Three such capsules daily would provide an excess of these components. In addition, most of these preparations include the RDA of vitamin E, which according to the study results appears to interfere with the beneficial action of vitamin A for RP when taken in high doses. TOP

Should I be concerned about getting the right amounts of vitamin A and vitamin E in my diet?

The average diet provides approximately 3,000-4,000 IU of vitamin A per day. In the clinical treatment trial, the actual average intake for the patients was 3,600 IU per day. This daily dietary amount was taken into account for the final recommendation of a supplement of 15,000 IU vitamin A palmitate per day as a treatment for RP. You should maintain a regular balanced diet, you should NOT try to specifically select foods that are high in vitamin A content. Also, you should NOT try to eliminate foods that are high in vitamin E content. TOP

Is there anything else I can do besides maintaining a balanced diet and taking vitamin A to preserve my vision?

At this time, there are no other approaches for preserving vision affected by RP that have been proved useful through a carefully controlled clinical treatment trial. Some doctors advise their patients to protect their eyes from bright light. As a precaution, individuals with RP are encouraged to protect their eyes from long-term exposure to bright sunlight until more is learned. Good quality sunglasses are useful for bright days outdoors. TOP

Should I be encouraged by the discovery of this treatment?

Yes, indeed! This breakthrough is a concrete reward for the many years of research that preceded it. Daily vitamin A supplementation is the first discovered means to partially control RP that is proved useful and safe for most patients. This clinical treatment trial has demonstrated that further ways to slow vision loss can now be proposed with the knowledge that it can be done. The trial is an extraordinary example of the value of carefully designed work. It was done under close monitoring for appropriate benefit and avoidance of risk to patients, and will serve as a model for future studies. TOP

Will other research on RP stop now that this treatment has been found?

No, just the opposite! The search for addition and improved treatments and the means to cure or prevent RP will continue. Studies on nutritional supplements represent only one aspect of the RP scientific research strategy. This disease must be understood at the most basic cellular level in order to understand how it is caused and how it can be stopped. Research in biochemistry and cell biology, as well as molecular genetics and clinical studies, will lead to the design and testing of other treatments that may stop the progression of the disease and ultimately prevent it from ever occurring.
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Old Tue, Sep-21-04, 09:12
Zuleikaa Zuleikaa is offline
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Default More on Vitamin A Dosage

http://www.ilsi.org/file/a5_pregnancy.pdf
Vitamin A is needed in increased amounts to support maternal reproductive processes, including fetal growth and development, and during lactation to replace losses in breast milk. The increased need during gestation is small and can be provided through a balanced diet and maternal reserves from well-nourished women.1 In areas of endemic vitamin A deficiency (VAD), however, vitamin A supplements often must supply this need. With lactation, requirements rise to replace maternal vitamin A lost daily in breast milk
and to maintain breast milk vitamin A at a level to protect the needs of rapidly growing infants during at least the first 6 months of life.2 Vitamin A requirements to support repetitive reproductive cycles may be difficult to meet from the affordable vegetarian-type diets typical of VAD areas,3 but they are easily provided through a high-dose or frequent low-dose vitamin A supplement. High doses of vitamin A given in early pregnancy can be unsafe, and it is operationally difficult to provide daily small doses in developing countries. Intervention programs to meet vitamin A needs of fertile women, therefore, must adjust dose levels and timing to ensure safety during pregnancy and lactation. Severe VAD in animals causes abortions, fetal death, resorptions, and congenital defects.4 These outcomes occur in rats when maternal tissue is depleted to the extent that reserves are decreased in the ocular system, one of the last tissues to loose its vitamin A supply.5 Case reports of adverse reproductive outcomes associated with human deficiency are rare and poorly documented. Available epidemiologic observations in human
populations where clinical vitamin A deficiency in children is common also rarely report adverse
reproductive outcomes. This is in spite of recognizing that reproductive-age women living in VAD areas frequently report night blindness during pregnancy and/or lactation6 and that nightblindness in women during periods of increased physiologic need is thought to reflect vitamin A deficiency. However, an
association of incident congenital ocular defects with VAD is suggested by a recent randomized community trial in pregnant Nepalese women. Ocular defects were reduced in their newborns by weekly low-dose vitamin A supplementation.7 High doses of vitamin A.retinol, retinyl ester, and their oxidized metabolites.given to animals in the International Vitamin A Consultative Group . IVACG
Intervention programs to meet vitamin A needs of fertile women must adjust dose levels and timing to ensure safety during pregnancy and lactation. early gestational period can cause congenital defects,8 and reports suggest impaired growth and behavioral response rates when high doses are given later in gestation.9,10 Dose and timing when adverse effects are noted are highly variable and species specific.
In humans, malformations similar to those seen in animals have been recorded when women ingested
high doses of preformed vitamin A and related compounds (particularly retinoic acid and analogues) in the first trimester.11 Retinoic acid and other oxidized metabolites are not used in VAD control programs and, in fertile women, only under medical supervision for specialized conditions when they are not pregnant. Birth defects from ingestion of retinol or retinyl ester, usually occur when the high-dose
supplement is taken daily for several days or weeks during the first gestational trimester.8 There is no
evidence of acute toxicity from ingesting ß-carotene or other carotenoids from supplements or food, especially at levels comparable to those recommended for vitamin A supplementation.11, 12 Night blindness is frequently reported in pregnant women living in areas where VAD is common in children,13 and breast milk from lactating women residing in these areas is often low in vitamin A.14 Night blindness during pregnancy has sometimes been reported to disappear without intervention following parturition, but may reappear during lactation and/or repeat pregnancies.6,13 Night blindness associated with pregnancy and lactation is reported to be only partially responsive to vitamin A supplementation,4,6,15 which suggests that other nutritional deficiencies may contribute to the problem. Breast milk levels of vitamin A in a population reflect habitual maternal vitamin A intakes, particularly when low. Low vitamin A levels have been safely increased in populations, including lactating women, when the ingestion of vitamin A. fortified food products becomes frequent16,17 and in individual mothers provided low-dose vitamin A supplements daily (2000 IU)18 or up to 300,000 IU in a single dose given within 1 month of parturition.19 Fully breast-feeding mothers are infertile for at least 8 weeks postpartum20 and, while amenorrheic, are of low susceptibility to pregnancy up to 6 months.21 The physiologic needs
for vitamin A of infants born to vitamin A.adequate mothers and fed breast milk with adequate vitamin A (in excess of 30 µg/dL or 1.05 µmol/L) are met for at least the first 6 months of life.2 The World Health Organization recently convened a group of experts to consider dose and safety issues in relationship to the
vitamin A needs of fertile women and their nursing infants.20 The consultation responded in part to a
single report questioning the safety of daily intakes during pregnancy of 10,000 IU vitamin A as a supplement given to adequately nourished women in the United States.22 Recently available global population-based information was also reviewed on the length of postpartum infertility, the period when it would be safe to give high doses of vitamin A to reproductive-age women. The review of both published and available unpublished data reconfirmed earlier recommendations of IVACG (1986) that: n It is safe to give fertile women, independent of their vitamin A status, as much as 10,000 IU (3000 µg RE) daily at any time during pregnancy. There is no evidence of acute toxicity from ingesting ß-carotene or other carotenoids from supplements or food, especially at levels comparable to those recommended for vitamin A supplementation. The recommendation was extended by noting that: n No benefits have been demonstrated from taking a supplement during gestation where habitual vitamin A intakes exceed about
three times the RDA (about 8000 IU or 2400 µg RE) from sources rich in provitamin A. The earlier recommendations of IVACG for supplementation of women residing in endemically deficient areas also were extended to include the following timing and doses: n A weekly supplement of up to 25,000 IU
(8500 µg RE) is a safe alternative to daily supplementation during pregnancy.* n A single high-dose supplement of up to 200,000 IU to breast-feeding women is safe up to 8 weeks postdelivery. n For non-breast-feeding women, a single high-dose supplement of up to 200,000 IU is safe up to 6 weeks postdelivery. Fortified food products can safely be ingested during pregnancy and lactation, and vitamin A rich natural foods, such as animal liver, consumed occasionally also can be safely ingested.20,23 There is no known teratogenic risk associated with prolonged consumption of either natural food sources or supplements rich in vitamin A.active carotenoids.8,12 *During the first 60 days following conception, the advisability of doses above 25,000 IU is uncertain. Risks are likely to diminish as gestation advances.
References
1. National Research Council/National Academy of Sciences. Recommended dietary allowances, 10th ed.
(report of the Subcommittee on the Tenth Edition of the RDAs, Food and Nutrition Board, Commission on Life Sciences). Washington, DC: National Academy Press, 1989;85
2. Underwood BA. Maternal vitamin A status and its importance in infancy and early childhood. Am J Clin Nutr 1994; 59(suppl):517S.524S
3. De Pee S et al. Lack of improvement in vitamin A status with increased consumption of dark-green leafy vegetables. Lancet 1995; 346:75.81
4. Wallingford JC, Underwood BA. Vitamin A deficiency in pregnancy, lactation, and the nursing child. In: Bauernfeind JC, ed. Vitamin A deficiency and its control. New York: Academic Press, 1986;101.152
5. Wallingford JC, Underwood BA. Vitamin A status needed to maintain vitamin A concentrations in nonhepatic tissues of the pregnant rat. J Nutr 1987;117:1410.1415
6. IVACG. Maternal night blindness: extent and associated risk factors. IVACG Statement. Washington, DC: IVACG, 1997
7. Khatry SK et al. Effect of maternal vitamin A or betacarotene supplementation on incidence of birth defects among Nepalese infants. In: Report of the XVIII IVACG Meeting, Cairo, 1997. Washington, DC: IVACG, 1998; 87
8. Hathcock JN et al. Evaluation of vitamin A toxicity. Am J Clin Nutr 1990;52:183.202
9. Hutchings DE, Gaston J. The effects of vitamin A excess administered during the mid-fetal period on learning and development in rat offspring. Dev Psychobiol 1974;71:225.233
10. Vorhees CV et al. The relationship of gestational age of vitamin A induced postnatal dysfunction. Teratology 1978;17:271.276
11. Teratology Society. Teratology Society position paper: recommendations for vitamin A use during pregnancy. Teratology 1987;35:269.275
12. Bendich A. The safety of ß-carotene. Nutr Cancer 1988;11:207.214
13. Katz J et al. Night blindness is prevalent during pregnancy and lactation in rural Nepal. J Nutr 1995;125:2122.2127
14. Newman V. Vitamin A and breastfeeding: a comparison of data from developed and developing countries. San Diego, CA: Wellstart International, 1993
15. Christian P et al. The impact of vitamin A or betacarotene
supplementation on the incidence of night blindness during pregnancy and lactation in Nepal. In:
Report of the XVIII IVACG Meeting, 1997. Washington, DC: IVACG, 1998; 86
16. Arroyave G et al. Evaluation of sugar fortification with vitamin A at the national level. Scientific Publication No. 384. Washington, DC: Pan American Health
Organization, 1979
17. Muhilal, Murdiana A, Axis I, et al. Vitamin A.fortified
monosodium glutamate and vitamin A status: a controlled field trial. Am J Clin Nutr 1988;48:1265.1270
18. Villard L, Bates CJ. Effect of vitamin A supplementation on plasma and breast milk vitamin A levels in poorly nourished Gambian women. Hum Nutr Clin Nutr 1987;


41C:47.58 Established in 1975, the International Vitamin A Consultative Group guides international activities for reducing vitamin A deficiency in the world. IVACG concentrates its efforts on stimulating and disseminating new knowledge, translating that new knowledge to assist others in its practical application, and providing authoritative policy statements and recommendations that
others can use to develop appropriate prevention and control programs. This statement was prepared at the request of the International Vitamin A Consultative Group (IVACG) by Dr. Barbara A.
Underwood, Food and Nutrition Board, Institute of Medicine, NAS, Washington, D.C., USA.

It was reviewed and approved by the IVACG Steering Committee: David Alnwick, MSc
Paul Arthur, MD, MPH, MSc
Omar Dary, PhD
Frances R. Davidson, PhD, IVACG Secretary
Abraham Horwitz, MD, MPH, IVACG Chair
Vinodini Reddy, MD, DCH, FIAP
Suttilak Smitasiri, PhD
Alfred Sommer, MD, MHSc, IVACG Steering Committee Chair
Keith P. West, Jr, DrPH

The publication of this statement is made possible by support from Opportunities for Micronutrient Interventions (OMNI), a
project of the Office of Health and Nutrition, Bureau for Global Programs, Field Support and Research, U.S. Agency for
International Development, under Contract HRN-5122-C-00-3025-00, Project 936-5122.
Printed June 1998 in the United States of America.
Additional copies of this and other IVACG publications are available free of charge to developing countries and for US$3.50 to
developed countries. Copies can be ordered from the IVACG Secretariat:
IVACG Secretariat . ILSI Research Foundation
1126 Sixteenth Street, NW . Washington, DC 20036-4810 . USA
International Vitamin A Consultative Group . IVACG
The ILSI Research Foundation.s Human Nutrition Institute serves as the IVACG Secretariat.

19. Stoltzfus RJ et al. High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant. J Nutr 1993;123:666.675
20. World Health Organization. Safe vitamin A dosage during pregnancy and lactation: recommendations and report of a consultation. Document NUT/98.4 (available from the Nutrition Programme) Geneva: WHO, 1998
21. Kennedy KI et al. Consensus statement: lactational amenorrhea method for family planning. Int J Gynecol Obstet 1996;54:55.57
22. Rothman KJ et al. Teratogenicity of high vitamin A intake. N Engl J Med 1995; 333:1369.1373
23. Buss NE et al. The teratogenic metabolites of vitamin A in women following supplements and liver. Hum Exp Toxicol 1994;13:33.43
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Old Tue, Sep-21-04, 12:38
cs_carver cs_carver is offline
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Default Maybe this is in the above...

1. That list of deficiencies could apply to just about any vitamin deficiency, not just A & D.

2. Didn't see if this was pointed out in the replies above--overdose of Vitamin A is, I believe, untreatably toxic and fatal. Read Geneen Roth's accidental self-overdose. Nearly died, lost all her hair, took months to recover. It got my attention.
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  #6   ^
Old Tue, Sep-21-04, 14:28
Zuleikaa Zuleikaa is offline
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Default

cs carver
Well, I guess Geneen Roth didn't die. I'm sorry, that was tactless and tasteless. But the point is she overdosed and she didn't die.

I am not advocating obscene amounts of either vitamins D or A. I would like people to have a more open mind about these two vitamins however. Especially given the rise of chronic, immunological, environmental diseases. Just about any vitamin/ drug has a toxic level. But the point I'm making is that there have been studies of people with these diseases and their reactions to, cures, remissions of diseases when treated with these to supplements. That is a causal link, not just saying these people had bad nutrition.



I am definitely not advocating that anyone overdose or even that they supplement if they don't have one of the indicated health problems.

Levels of vitamin D and A and their deficiency can be tested.

Perhaps this will help clairfy what amounts of A are recommended and what amounts are toxic. It might also clarify might clarify some of the issues around vitamin A.

http://lpi.oregonstate.edu/infocent...amins/vitaminA/
VITAMIN A

NOTE: There are some great and quite clear charts that don't come out here so I would encourage you to click the link.

Vitamin A is a generic term for a large number of related compounds. Retinol (an alcohol) and retinal (an aldehyde) are often referred to as preformed vitamin A. Retinal can be converted by the body to retinoic acid, the form of vitamin A known to affect gene transcription. Retinol, retinal, retinoic acid, and related compounds are known as retinoids. Beta-carotene and other carotenoids that can be converted by the body into retinol are referred to as provitamin A carotenoids. Hundreds of different carotenoids are synthesized by plants, but only about 10 % of them are provitamin A carotenoids (1). The following discussion will focus mainly on preformed vitamin A and retinoic acid.

FUNCTION

Vision

The retina is located at the back of the eye. When light passes through the lens, it is sensed by the retina and converted to a nerve impulse for interpretation by the brain. Retinol is transported to the retina via the circulation, where it moves into retinal pigment epithelial cells (diagram). There, retinol is esterified to form a retinyl ester, which can be stored. When needed, retinyl esters are broken apart (hydrolyzed) and isomerized to form 11-cis retinol, which can be oxidized to form 11-cis retinal. 11-cis Retinal can be shuttled across the interphotoreceptor matrix to the rod cell, where it binds to a protein called opsin to form the visual pigment, rhodopsin (visual purple). Rod cells with rhodopsin can detect very small amounts of light, making them important for night vision. Absorption of a photon of light catalyzes the isomerization of 11-cis retinal to all-trans retinal and results in its release. This isomerization triggers a cascade of events, leading to the generation of an electrical signal to the optic nerve. The nerve impulse generated by the optic nerve is conveyed to the brain where it can be interpreted as vision. Once released all-trans retinal is converted to all-trans retinol, which can be transported across the interphotoreceptor matrix to the retinal epithelial cell to complete the visual cycle (2). Inadequate retinol available to the retina results in impaired dark adaptation, known as "night blindness."

Regulation of gene expression

Retinoic acid (RA) and its isomers act as hormones to affect gene expression and thereby influence numerous physiological processes. All-trans RA and 9-cis RA are transported to the nucleus of the cell bound to cytoplasmic retinoic acid-binding proteins (CRABP). Within the nucleus, RA binds to retinoic acid receptor proteins (diagram). All-trans RA binds to retinoic acid receptors (RAR) and 9-cis RA binds to retinoid receptors (RXR). RAR and RXR form RAR/RXR heterodimers, which bind to regulatory regions of the chromosome called retinoic acid response elements (RARE). A dimer is a complex of two protein molecules. Heterodimers are complexes of two different proteins, while homodimers are complexes of two of the same protein. Binding of all-trans RA and 9-cis RA to RAR and RXR respectively allows the complex to regulate the rate of gene transcription, thereby influencing the synthesis of certain proteins used throughout the body. RXR may also form heterodimers with thyroid hormone receptors (THR) or vitamin D receptors (VDR). In this way, vitamin A, thyroid hormone, and vitamin D may interact to influence gene transcription (3). Through the stimulation and inhibition of transcription of specific genes, retinoic acid plays a major role in cellular differentiation, the specialization of cells for highly specific physiological roles. Most of the physiological effects attributed to vitamin A appear to result from its role in cellular differentiation.

Immunity

Vitamin A is commonly known as the anti-infective vitamin, because it is required for normal functioning of the immune system (4). The skin and mucosal cells (cells that line the airways, digestive tract, and urinary tract) function as a barrier and form the body's first line of defense against infection. Retinol and its metabolites are required to maintain the integrity and function of these cells (5). Vitamin A and retinoic acid (RA) play a central role in the development and differentiation of white blood cells, such as lymphocytes that play critical roles in the immune response. Activation of T-lymphocytes, the major regulatory cells of the immune system, appears to require all-trans RA binding of RAR (3).

Growth and Development

Both vitamin A excess and deficiency are known to cause birth defects. Retinol and retinoic acid (RA) are essential for embryonic development (4). During fetal development, RA functions in limb development and formation of the heart, eyes, and ears (6). Additionally, RA has been found to regulate expression of the gene for growth hormone.

Red blood cell production

Red blood cells, like all blood cells, are derived from precursor cells called stem cells. These stem cells are dependent on retinoids for normal differentiation into red blood cells. Additionally, vitamin A appears to facilitate the mobilization of iron from storage sites to the developing red blood cell for incorporation into hemoglobin, the oxygen carrier in red blood cells (2, 7).

Nutrient Interactions

Zinc and vitamin A: Zinc deficiency is thought to interfere with vitamin A metabolism in several ways: 1) Zinc deficiency results in decreased synthesis of retinol binding protein (RBP), which transports retinol through the circulation to tissues (e.g., the retina). 2) Zinc deficiency results in decreased activity of the enzyme that releases retinol from its storage form, retinyl palmitate, in the liver. 3) Zinc is required for the enzyme that converts retinol into retinal (8, 9). At present, the health consequences of zinc deficiency on vitamin A nutritional status in humans are unclear (10).

Iron and vitamin A: Vitamin A deficiency may exacerbate iron deficiency anemia. Vitamin A supplementation has been shown to have beneficial effects on iron deficiency anemia and improve iron nutritional status among children and pregnant women. The combination of vitamin A and iron seems to reduce anemia more effectively than either iron or vitamin A alone (11).

DEFICIENCY

Vitamin A deficiency and vision

Vitamin A deficiency among children in developing nations is the leading preventable cause of blindness (12). The earliest evidence of vitamin A deficiency is impaired dark adaptation or night blindness. Mild vitamin A deficiency may result in changes in the conjunctiva (corner of the eye) called Bitot's spots. Severe or prolonged vitamin A deficiency causes a condition called xeropthalmia (dry eye), characterized by changes in the cells of the cornea (clear covering of the eye) that ultimately result in corneal ulcers, scarring, and blindness (4, 8).

Vitamin A deficiency and infectious disease

Vitamin A deficiency can be considered a nutritionally acquired immunodeficiency disease (13). Even children who are only mildly deficient in vitamin A have a higher incidence of respiratory disease and diarrhea, as well as a higher rate of mortality from infectious disease, than children who consume sufficient vitamin A (14). Supplementation of vitamin A has been found to decrease the severity of and deaths from diarrhea and measles in developing countries, where vitamin A deficiency is common (15). HIV-infected women who were vitamin A deficient were three to four times more likely to transmit HIV to their infants (16). The onset of infection reduces blood retinol levels very rapidly. This phenomenon is generally believed to be related to decreased synthesis of retinol binding protein (RBP) by the liver. In this manner, infection stimulates a vicious cycle, because inadequate vitamin A nutritional status is related to increased severity and likelihood of death from infectious disease (17).

The Recommended Dietary Allowance (RDA)

The RDA for vitamin A was revised by the Food and Nutrition Board (FNB) of the Institute of Medicine in 2001. The latest RDA is based on the amount needed to ensure adequate stores of vitamin A in the body to support normal reproductive function, immune function, gene expression, and vision (18).

Recommended Dietary Allowance (RDA) for Vitamin A as Preformed Vitamin A (Retinol)

Life Stage Age Males: mcg/day (IU/day) Females: mcg/day (IU/day)
Infants 0-6 months 400 (1333 IU) 400 (1333 IU)
Infants 7-12 months 500 (1667 IU) 500 (1667 IU)
Children 1-3 years 300 (1000 IU) 300 (1000 IU)
Children 4-8 years 400 (1333 IU) 400 (1333 IU)
Children 9-13 years 600 (2000 IU) 600 (2000 IU)
Adolescents 14-18 years 900 (3000 IU) 700 (2333 IU)
Adults 19 years and older 900 (3000 IU) 700 (2333 IU)
Pregnancy 18 years and younger - 750 (2500 IU)
Pregnancy 19-years and older - 770 (2567 IU)
Breastfeeding 18 years and younger - 1,200 (4000 IU)
Breastfeeding 19-years and older - 1,300 (4333 IU)

DISEASE PREVENTION

Cancer

Studies in cell culture and animal models have documented the capacity for natural and synthetic retinoids to reduce carcinogenesis significantly in skin, breast, liver, colon, prostate, and other sites (2). However, the results of human studies examining the relationship between the consumption of preformed vitamin A and cancer are less clear.

Lung cancer: At least ten prospective studies have compared blood retinol levels at baseline among people who subsequently developed lung cancer and those who did not. Only one of those studies found a statistically significant inverse association between serum retinol and lung cancer risk (19). The results of the Beta-Carotene And Retinol Efficacy Trial (CARET) suggest that high-dose supplementation of vitamin A and b-carotene should be avoided in people at high risk of lung cancer (20). About 9,000 people (smokers and people with asbestos exposure) were assigned a daily regimen of 25,000 IU of retinol and 30 milligrams of b-carotene, while a similar number of people were assigned a placebo. After four years of follow up the incidence of lung cancer was 28% higher in the supplemented group. Presently, it seems unlikely that increased retinol intake decreases the risk of lung cancer, although the effects of retinol may be different for nonsmokers compared to smokers (19).

Breast cancer: Retinol and its metabolites have been found to reduce the growth of breast cancer cells in the test tube, but observational studies of dietary retinol intake in humans have been less optimistic (21). The majority of epidemiologic studies have failed to find significant associations between retinol intake and breast cancer risk in women (22-25), although one large prospective study found total vitamin A intake to be inversely associated with the risk of breast cancer in premenopausal women with a family history of breast cancer (26). Blood levels of retinol reflect the intake of both preformed vitamin A and provitamin A carotenoids like b-carotene. Although a recent case-control study found serum retinol levels and serum antioxidant levels to be inversely related to the risk of breast cancer (27), two recent prospective studies did not observe significant associations between blood retinol levels and the subsequent risk of developing breast cancer (28, 29). Presently, there is little evidence in humans that increased intake of preformed vitamin A or retinol reduces breast cancer risk.

DISEASE TREATMENT

Pharmacologic doses of retinoids

It is important to note that treatment with high doses of natural or synthetic retinoids overrides the body's own control mechanisms, and therefore carries with it risks of side effects and toxicity. Additionally, all of these compounds have been found to cause birth defects. Women who have a chance of becoming pregnant should avoid treatment with these medications. Retinoids tend to be very long acting; side effects and birth defects have been reported to occur months after discontinuing retinoid therapy (2). The retinoids discussed below are prescription drugs, and should not be used without medical supervision.

Retinitis pigmentosa

Retinitis pigmentosa describes a broad spectrum of genetic disorders that result in the progressive loss of photoreceptor cells (rods and cones) in the eye's retina (30). Early symptoms of retinitis pigmentosa include impaired dark adaptation and night blindness, followed by the progressive loss of peripheral and central vision over time. The results of a randomized controlled trial in more than 600 patients with common forms of retinitis pigmentosa indicated that supplementation with 4,500 mcg (15,000 IU)/day of preformed vitamin A (retinol) significantly slowed the loss of retinal function over a period of 4-6 years (31). In contrast, supplementation with 400 IU/day of vitamin E increased the loss of retinal function by a small but significant amount, suggesting that patients with common forms of retinitis pigmentosa may benefit from long term vitamin A supplementation but should avoid vitamin E supplementation at levels higher than those found in a typical multivitamin. Up to 12 years of follow-up in these patients did not reveal any signs of liver toxicity as a result of excess vitamin A intake (32). High dose vitamin A supplementation to slow the course of retinitis pigmentosa requires medical supervision and must be discontinued if there is a possibility of pregnancy (see Safety).

Acute promyelotic leukemia

Normal differentiation of myeloid stem cells in the bone marrow gives rise to platelets, red blood cells, and white blood cells, which are important for the immune response. Altered differentiation of those stem cells results in the proliferation of immature leukemic cells, giving rise to leukemia. A mutation of the retinoic acid receptor RAR has been discovered in patients with a specific type of leukemia called acute promyelotic leukemia (APL). Treatment with all-trans retinoic acid or high doses of all-trans retinyl palmitate restores normal differentiation, and leads to improvement in some APL patients (2,17).

Diseases of the skin

Both natural and synthetic retinoids have been used as pharmacologic agents to treat disorders of the skin. Etretinate and acitretin are retinoids that have been useful in the treatment of psoriasis, while tretinoin (Retin-A) and isotretinoin (Accutane) have been used successfully to treat severe acne. Retinoids most likely affect the transcription of skin growth factors and their receptors (2).

SOURCES

Retinol activity equivalency (RAE)

Different dietary sources of vitamin A have different potencies. For example, beta-carotene is less easily absorbed than retinol and must be converted to retinal and retinol by the body. The most recent international standard of measure for vitamin A is retinol activity equivalency (RAE), which represents vitamin A activity as retinol. Two micrograms (mcg) of beta-carotene in oil provided as a supplement can be converted by the body to 1 mcg of retinol giving it an RAE ratio of 2:1. However, 12 mcg of beta-carotene from foods are required to provide the body with 1 mcg of retinol, giving dietary beta-carotene an RAE ratio of 12:1. Other provitamin A carotenoids in foods are less easily absorbed than beta-carotene, resulting in RAE ratios of 24:1. The RAE ratios for beta-carotene and other provitamin A carotenoids are shown in the table below (18). An older international standard, still commonly used, is the international unit (IU). One IU is equivalent to 0.3 mcg of retinol.

Retinol activity equivalency (RAE) ratios for beta-carotene and other provitamin A carotenoids

Quantity Consumed Quantity Bioconverted to Retinol RAE ratio
1 mcg of dietary or supplemental vitamin A 1 mcg of retinol* 1:1
2 mcg of supplemental beta-carotene 1 mcg of retinol 2:1
12 mcg of dietary beta-carotene 1 mcg of retinol 12:1
24 mcg of dietary alpha-carotene 1 mcg of retinol 24:1
24 mcg of dietary beta-cryptoxanthin 1 mcg of retinol 24:1

*One IU is equivalent to 0.3 mcg of retinol, and one mcg of retinol is equivalent to 3.33 IU of retinol.

Food sources

Free retinol is not generally found in foods. Retinyl palmitate, a precursor and storage form of retinol, is found in foods from animals. Plants contain carotenoids, some of which are precursors for vitamin A (e.g., alpha-carotene and beta-carotene). Yellow and orange vegetables contain significant quantities of carotenoids. Green vegetables also contain carotenoids, though the pigment is masked by the green pigment of chlorophyll (1). A number of good food sources of vitamin A are listed in the table below along with their vitamin A content in retinol activity equivalents (mcg RAE). In those foods where retinol activity comes mainly from provitamin A carotenoids, the carotenoid content and the retinol activity equivalents are presented. You may use the USDA food composition database to check foods for their content of several different carotenoids, including lycopene, lutein and zeaxanthin.

Food Serving Vitamin A, RAE
Vitamin A, IU Retinol, mcg Retinol, IU
Cod liver oil 1 teaspoon 1,350 mcg 4,500 IU 1,350 mcg 4,500 IU
Fortified breakfast cereals 1 serving 150-230 mcg 500-767 IU 150-230 mcg 500-767 IU
Egg 1 large 91 mcg 303 IU 89 mcg 296 IU
Butter 1 tablespoon 97 mcg 323 IU 95 mcg 317 IU
Whole milk 1 cup (8 fl ounces) 68 mcg 227 IU 68 mcg 227 IU
2% fat milk (vitamin A added) 1 cup (8 fl ounces) 134 mcg 447 IU 134 mcg 447 IU
Nonfat milk (vitamin A added) 1 cup (8 fl ounces) 149 mcg 500 IU 149 mcg 500 IU
Sweet potato 1/2 cup, mashed 959 mcg 3,196 IU 0 0
Carrot (raw) 1/2 cup, chopped 385 mcg 1,283 IU 0 0
Cantaloupe 1/2 medium melon 466 mcg 1,555 IU 0 0
Spinach 1/2 cup, cooked 472 mcg 1,572 IU 0 0
Squash, butternut 1/2 cup, cooked 572 mcg 1,906 IU 0 0

Supplements

The principal forms of preformed vitamin A (retinol) in supplements are retinyl palmitate and retinyl acetate. Beta-carotene is also a common source of vitamin A in supplements, and many supplements provide a combination of retinol and beta-carotene (33). If a percentage of the total vitamin A content of a supplement comes from beta-carotene, this information is included in the Supplement Facts label under vitamin A (see example supplement label). Most multivitamin supplements available in the U.S. provide 1,500 mcg (5,000 IU) of vitamin A, substantially more than the current RDA for vitamin A. This is due to the fact that the Daily Values (DV) used by the FDA for supplement labeling are based on the RDAs established in 1968 rather than the most recent RDAs, and multivitamin supplements typically provide 100% of the DV for most nutrients. Because retinol intakes of 5,000 IU/day have recently been associated with an increased risk of osteoporosis in older adults (see Safety), some companies have reduced the retinol content in their multivitamin supplements to 750 mcg (2,500 IU).

SAFETY

Toxicity

The condition caused by vitamin A toxicity is called hypervitaminosis A. It is caused by overconsumption of preformed vitamin A, not carotenoids. Preformed vitamin A is rapidly absorbed and slowly cleared from the body, so toxicity may result acutely from high-dose exposure over a short period of time, or chronically from much lower intake (2). Vitamin A toxicity is relatively rare. Symptoms include nausea, headache, fatigue, loss of appetite, dizziness, and dry skin. Signs of chronic toxicity include, dry itchy skin, loss of appetite, headache, and bone and joint pain. Severe cases of hypervitaminosis A may result in liver damage, hemorrhage, and coma. Generally, signs of toxicity are associated with long-term consumption of vitamin A in excess of 10 times the RDA (8,000 to 10,000 mcg/day or 25,000 to 33,000 IU/day). However, there is evidence that some populations may be more susceptible to toxicity at lower doses, including the elderly, chronic alcohol users, and some people with a genetic predisposition to high cholesterol (9). In January 2001, the Food and Nutrition Board (FNB) of the Institute of Medicine set the tolerable upper level (UL) of vitamin A intake for adults at 3,000 mcg (10,000 IU)/day of preformed vitamin A (18).

Tolerable Upper Level of Intake (UL) for Preformed Vitamin A (Retinol)

Age Group UL in mcg/day (IU/day)
Infants 0-12 months 600 (2,000 IU)
Children 1-3 years 600 (2,000 IU)
Children 4-8 years 900 (3,000 IU)
Children 9-13 years 1,700 (5,667 IU)
Adolescents 14-18 years 2,800 (9,333 IU)
Adults 19 years and older 3,000 (10,000 IU)

Safety in pregnancy

Although normal fetal development requires sufficient vitamin A intake, consumption of excess preformed vitamin A (retinol) during pregnancy is known to cause birth defects. No increase in the risk of vitamin A-associated birth defects has been observed at doses of preformed vitamin A from supplements below 3,000 mcg/day (10,000 IU/day) (18). Since a number of foods in the U.S. are fortified with preformed vitamin A, pregnant women should avoid multivitamin or prenatal supplements that contain more than 1,500 mcg (5,000 IU) of vitamin A (34). Vitamin A from beta-carotene is not known to increase the risk of birth defects. Etretinate and isotretinoin (Accutane), synthetic derivatives of retinol, are known to cause birth defects and should not be taken during pregnancy or if there is a possibility of becoming pregnant. Tretinoin (Retin-A), another retinol derivative, is prescribed as a topical preparation that is applied to the skin. Because of the potential for systemic absorption of topical tretinoin, its use during pregnancy is not recommended.

Do high intakes of vitamin A increase the risk of osteoporosis?

The results of several recent prospective studies suggest that long term intakes of preformed vitamin A in excess of 1,500 mcg/day (5,000 IU/day) are associated with increased risk of osteoporotic fracture and decreased bone mineral density (BMD) in older men and women.(35-37) Although this level of intake is greater than the RDA of 700-900 mcg/day (2,300-3,000 IU/day), it is substantially lower than the UL of 3,000 mcg/day (10,000 IU/day). Only excess intakes of preformed vitamin A (retinol), not beta-carotene, were associated with adverse effects on bone health. Although these observational studies cannot provide the reason for the association between excess retinol intake and osteoporosis, limited experimental data suggest that excess retinol may stimulate bone resorption (38) or interfere with the ability of vitamin D to maintain calcium balance (39). In the U.S., retinol intakes in excess of 5,000 IU/day can be easily attained by those who regularly consume multivitamin supplements and/or fortified foods, including some breakfast cereals. At the other end of the spectrum, a significant number of elderly people have insufficient vitamin A intakes, which have also been associated with decreased BMD. One study of elderly men and women found that BMD was optimal at vitamin A intakes close to the RDA (36). Until supplements and fortified foods are reformulated to reflect the current RDA for vitamin A, it makes sense to look for multivitamin supplements that contain 2,500 IU of vitamin A or multivitamin supplements that contain 5,000 IU of vitamin A, of which at least 50% comes from beta-carotene (see example supplement label).

Drug Interactions

Chronic alcohol consumption results in depletion of liver stores of vitamin A, and may contribute to alcohol-induced liver damage (40). However, the liver toxicity of preformed vitamin A (retinol) is enhanced by chronic alcohol consumption, thus narrowing the therapeutic window for vitamin A supplementation in alcoholics (41). Oral contraceptives that contain estrogen and progestin increase retinol binding protein (RBP) synthesis by the liver, increasing the export of RBP-retinol complex in the blood. Whether this increases the dietary requirement of vitamin A is not known. Retinoids or retinoid analogs, including acitretin, all-trans-retinoic acid, bexarotene, etretinate and isotretinoin (Accutane), should not be used in combination with vitamin A supplements, because they may increase the risk of vitamin A toxicity (33).

THE LINUS PAULING INSTITUTE RECOMMENDATION

The RDA for vitamin A (2,300 IU/day for women and 3,000 IU/day for men) is sufficient to support normal gene expression, immune function, and vision. However, following the Linus Pauling Institute’s recommendation to take a multivitamin/multimineral supplement daily could supply as much as 5,000 IU/day of vitamin A as retinol, the amount that has been associated with adverse effects on bone health in older adults. For this reason, we recommend taking a multivitamin/multimineral supplement that provides no more than 2,500 IU of vitamin A or a supplement that provides 5,000 IU of vitamin A, of which at least 50% comes from beta-carotene (see example supplement label). High potency vitamin A supplements should not be used without medical supervision due to the risk of toxicity.

Older adults (65 years and older)

Presently there is little evidence that the requirement for vitamin A in older adults differs from that of younger adults. Additionally, vitamin A toxicity may occur at lower doses in older adults than in younger adults. Following the Linus Pauling Institute’s recommendation to take a multivitamin/multimineral supplement daily could supply as much as 5,000 IU/day of retinol, the amount that has been associated with adverse effects on bone health in older adults. For this reason, we recommend taking a multivitamin/multimineral supplement that provides no more than 2,500 IU of vitamin A or a supplement that provides 5,000 IU of vitamin A, of which at least 50% comes from beta-carotene (see example supplement label). High potency vitamin A supplements should not be used without medical supervision due to the risk of toxicity.

REFERENCES


--------------------------------------------------------------------------------

Written by:
Jane Higdon, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed by:
Norman I. Krinsky, Ph.D., Professor, Emeritus
Department of Biochemistry
Tufts University School of Medicine
USDA Human Nutrition Research Center on Aging

Do high intakes of vitamin A increase the risk of osteoporosis?
Reviewed by
Diane Feskanich, Sc.D.
Instructor in Medicine, Harvard Medical School
Associate Epidemiologist, Brigham and Women's Hospital

Last updated 12/12/2003 Copyright 2000-2003 The Linus Pauling Institute
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http://www.emersonecologics.com/Newswire.asp?id=277
Challenging the Vitamin A–Hip Fracture Link

A Healthnotes Newswire Opinion

By Alan R. Gaby, MD

Healthnotes Newswire (January 31, 2002)—Long-term consumption of a diet high in vitamin A can increase the risk of hip fractures in postmenopausal women, according to a recent study in the Journal of the American Medical Association.1 However, after carefully reviewing the new research, this scientist is not convinced.

In 1980, some 72,337 postmenopausal women participating in the Nurses' Health Study filled out a questionnaire concerning diet and use of nutritional supplements; the information was then updated periodically in subsequent years. In the 18-year follow-up period, 603 hip fractures resulting from low or moderate trauma (i.e., fractures presumably due to osteoporosis) occurred among study participants. Women who consumed the most vitamin A from food and supplements (i.e., those in the top 20%) had an 89% higher risk of hip fracture, compared with those consuming the least vitamin A (bottom 20%). Among women not taking vitamin A supplements, those with the highest dietary intake had a 69% higher risk of hip fracture, compared with those ingesting the least vitamin A. When vitamin A from supplements was considered separately, there was no statistically significant association with fracture risk, although there was a trend toward increased risk with increasing levels of supplementation.

Surprisingly small amounts of vitamin A were needed to increase a woman's fracture risk: as little as 6,667 IU per day when considering food in addition to supplements, and 3,333 IU per day when considering diet alone. Beta-carotene, a dietary constituent similar to vitamin A, was not associated with fracture risk and was not included in the analysis of vitamin A intake.

If the results of this study are to be taken at face value, then vitamin A can cause adverse effects on bone health at a level well below that which is typically associated with toxicity. Even 10,000 IU of supplemental vitamin A (an amount found in many multiple-vitamin preparations) would be above the safety threshold, and as little as 5,000 IU per day of supplemental vitamin A would be bordering on too much. Eating as little as one three-ounce serving of liver every ten days would, by itself, put a woman's dietary vitamin A intake over the top.

However, there is reason to question the assertion that relatively small amounts of vitamin A might lead to osteoporosis and hip fractures, because that conclusion is not consistent with the known actions of the vitamin. While vitamin A toxicity does adversely affect bone, the amounts required to produce such effects are extremely large. For example, in a study in rats, supplementation with vitamin A in amounts equivalent to a human dose of 20 million IU per day for five weeks inhibited the healing of fractures and resulted in the formation of fragile bones. However, half that amount (equivalent to a human dose of approximately 10 million IU per day for five weeks) actually accelerated fracture healing.2 Well-known consequences of chronic vitamin A toxicity in humans, which requires long-term intake of at least 33,300 IU per day, include hair loss, neurological problems, headaches, liver damage, visual impairment, and dry skin. Osteoporosis, on the other hand, has not been previously reported. It is difficult to believe, therefore, that intakes more than 80% lower than the chronic toxicity threshold would lead to bone loss.

A more likely explanation for the recent findings is that vitamin A intake is merely a marker for certain dietary patterns associated with osteoporosis. The main food sources of vitamin A in the American diet, aside from liver, are fortified skim and low-fat milk (5,000 IU per liter), fortified breakfast cereals (up to 1,250 IU per serving), and fortified margarine (approximately 500 IU per tablespoon). A daily diet that includes two cups of fortified milk plus either one serving of fortified breakfast cereal or two tablespoons of margarine would put a person in the top category of vitamin A intake.

There is circumstantial evidence that some or all of the foods high in vitamin A can promote the development of osteoporosis, for reasons unrelated to their vitamin A content. For example, fortified breakfast cereals often contain large amounts of added sugar. A high intake of refined sugar has been shown to increase urinary calcium excretion in humans and to cause bone loss in experimental animals.3 4 Most brands of margarine contain substantial quantities of compounds known as trans-fatty acids, which are produced during the manufacturing process. Ingestion of these trans-fatty acids can promote a deficiency of essential fatty acids,5 nutrients essential for normal bone health.6 Fortified milk, another significant dietary source of vitamin A, may also be a less-than-perfect food for the bones, despite its high calcium content. Milk is one of the major sources of dietary phosphorus, a mineral that is often present in excessive amounts in the American diet. Consumption of too much phosphorus can impair bone health, particularly in older women.7 In addition, dairy products are the only significant dietary source of naturally occurring trans-fatty acids.8 Studies examining the relationship between milk consumption and bone health have yielded conflicting results,9 and one study (using data from the same Nurses' Health Study described above) showed an increased risk of fractures in women who consumed two or more glasses of milk per day, compared with women consuming one glass or less per week.10

Liver, the other major dietary source of vitamin A, accumulates various environmental toxins, including lead and cadmium,11 both of which can cause osteoporosis. In addition, some environmental chemicals that might concentrate in the liver may conceivably promote bone loss through their capacity to inhibit the activity of certain hormones (androgens).12

Based on these considerations, it is difficult to conclude that the reported association between vitamin A intake and hip fractures represents a cause-effect relationship. Perhaps the real culprits are refined sugar, trans-fatty acids, milk, and environmental toxins.

References:

1. Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA 2002;287:47–54.
2. Udupa KN, Gupta LP. Role of vitamin A in the repair of fracture. Indian J Med Res 1966;54:1122–30.
3. Lemann J Jr, Piering WF, Lennon EJ. Possible role of carbohydrate-induced calciuria in calcium oxalate kidney-stone formation. N Engl J Med 1969;280:232–7.
4. Saffar JL, Sagroun B, de Tessieres C, Makris G. Osteoporotic effect of a high-carbohydrate diet (Keyes 2000) in golden hamsters. Arch Oral Biol 1981;26:393–7.
5. Holman RT, Aaes-Jorgensen E. Effects of trans fatty acid isomers upon essential fatty acid deficiency in rats. Proc Soc Exp Biol Med 1956;93:175–9.
6. Odutuga AA. Effects of low-zinc status and essential fatty acid deficiency on bone development and mineralization. Comp Biochem Physiol 1982;71A:383–8.
7. Calvo MS, Park YK. Changing phosphorus content of the U.S. diet: potential for adverse effects on bone. J Nutr 1996;126:1168S–80S.
8. Oomen CM, Ocke MC, Feskens EJM, et al. Association between trans fatty acid intake and 10-year risk of coronary heart disease in the Zutphen Elderly Study: a prospective population-based study. Lancet 2001;357:746–51.
9. Weinsier RL, Krumdieck CL. Dairy foods and bone health: examination of the evidence. Am J Clin Nutr 2000;72:681–9.
10. Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. Am J Public Health 1997;87:992–7.
11. Boyer KW, Jones JW, Linscott D, et al. Trace element levels in tissues from cattle fed a sewage sludge-amended diet. J Toxicol Environ Health 1981;8:281–95.
12. Sohoni P, Sumpter JP. Several environmental oestrogens are also anti-androgens. J Endocrinol 1998;158:327–39.

Alan R. Gaby, MD, an expert in nutritional therapies, served as a member of the Ad-Hoc Advisory Panel of the National Institutes of Health Office of Alternative Medicine. He is the Medical Editor for Clinical Essentials Alert, is the author of Preventing and Reversing Osteoporosis (Prima, 1994), and co-author of The Natural Pharmacy, 2nd Edition (Healthnotes, Prima, 1999), the A–Z Guide to Drug-Herb-Vitamin Interactions (Healthnotes, Prima, 1999), Clinical Essentials Volume 1 and 2 (Healthnotes, 2000), and The Patient’s Book of Natural Healing (Prima, 1999). Currently he is the Endowed Professor of Nutrition at Bastyr University of Natural Health Sciences, Kenmore, WA.

Copyright © 2001 Healthnotes, Inc. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
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