Subject: vitamin A toxicity
Croft Woodruff
From: John Cannell, MD <vitamin...@charterinternet.com>
Subject: vitamin A toxicity
To: "ripplenorth...@yahoo.com" <ripplenorth...@yahoo.com>
Received: Sunday, November 30, 2008, 8:33 PMThe Vitamin D NewsletterDecember, 2008
This is a periodic newsletter from the Vitamin D Council, a non-profit trying to end the epidemic of vitamin D deficiency. This newsletter is not copyrighted. Please reproduce it and post it on Internet sites. Our webmaster will post this newsletter on the website.
Dear Dr. Cannell:
I am angry that you sent the paper written by sixteen prominent nutrition experts warning about the dangers of cod liver oil and vitamin A without providing a way for me to read the entire paper for free. Medical papers should be open access, not pay-per-view.
Carole, New York
Dear Carole:
What you mean is why didn't the Vitamin D Council pay to publish in an open access journal so you would not have to pay to read it? Because we don't have enough money in our account, that's why.
We published a paper on influenza in an open access journal earlier this year but it cost the Vitamin D Council $1,800.00! Open access is not free; someone pays, if not you, then we do. However, it's nice to be able to read the entire paper for free, the goal many of us have for all scientific papers.
Our second influenza paper is free and is relevant to the coming cold and flu season. It has an unbelievable quote from a 1919 Public Health Service physician who was trying to prove how influenza was transmitted, using volunteers from the Navy. Remember, 300,000 Americans had just died from influenza. Would you volunteer like they did? Why didn't any of the volunteers get sick?
It is also nice that the Vitamin D Council's second influenza paper is the most downloaded paper the last 12 months in Virology Journal, although it has only been out only 9 months.
Top 20 most accessed articles in Virology Journal for the past year
It is also the most downloaded paper in the last 30 days, again, in spite of being out for 9 months.
Top 20 most accessed articles in Virology Journal for the past 30 days
It seems as if someone, somewhere, is rethinking the idea that vaccinating everyone for everything may not be the best approach. The number of vaccines pointing at our children continue to increase, virtually every year.
Others have written, asking why they can't read the abstract of the vitamin A toxicity paper. Editorials seldom have abstracts. Again, here is the full citation, the names of all sixteen experts, and a link that makes you pay $20.00 to the publisher (not to us) for the full paper. However, before you pay the $20.00, read the extensive quotes below, starting on the next page.
Dear Dr. Cannell:Can you quote from the paper, telling us why so many experts condemned cod liver oil?Robert, California
Dear Robert:
I don't know if copyright laws allow the author to do that, but I will take the chance. The crux of the problem is that a form of vitamin A, retinoic acid, weakly activates the vitamin D response element on the gene and perhaps blocks vitamin D's more robust activation. The first paper below is free to download. As the authors say, "there is a profound inhibition of vitamin D-activated . . . gene expression by retinoic acid."
Thompson PD, et al. Heterodimeric DNA binding by the vitamin D receptor and retinoid X receptors is enhanced by 1,25-dihydroxyvitamin D3 and inhibited by 9-cis-retinoic acid. Evidence for allosteric receptor interactions. J Biol Chem. 1998 Apr 3;273(14):8483-91.
The key is having the proper ratio of vitamin D to vitamin A in your body. To obtain this proper D/A ratio, you must make a choice. (1) Either obtain the D/A ratio Nature and God intended, that is, the ratio the human genome evolved on, or (2) think you know everything, intervene in a closed system, bypass the controls in the intestine and inject active A directly into your blood by taking vitamin A or cod liver oil. Vitamin A production is tightly controlled in the body, the source (substrate) being carotenoids from vegetables in your intestine. The body uses these carotenoid substrates to make exactly the right amount of retinol for your body. That is, it is a closed, tightly regulated, system, one designed to perfection by God and Nature. When you take vitamin A as retinol, such as in cod liver oil, you intervene in this closed system and bypass the controls. Proceed at your peril.
Vitamin D is also a closed controlled system and I don't recommend intervening in that system either. Vitamin D is a substrate, like carotenoids, it is not the active substance. Taking vitamin A as retinol is like taking activated vitamin D, calcitriol. Doing so bypasses controls and I have never recommended anyone take activated vitamin D except patients with renal failure under the care of a nephrologist. As long as your vitamin D dose is not excessive, you are not intervening in a closed system, you are simply providing the vitamin D substrate. The body, if and when it has enough vitamin D substrate, will use what it needs and dispose or store the rest.
Thus the goal is to provide all the vitamin A and vitamin D substrate the body would have obtained in a natural state, so the body can regulate both systems naturally. This is best done by eating colorful vegetables and by exposing your naked skin to equatorial sun every day. Since most of us can't do the later, and won't do the former, we have to take the same amount of vitamin D substrate we would have gotten if we lived 100,000 years ago, and may want to take beta-carotene substrate in a multivitamin. As far as I know, low doses of beta-carotene (1,000 to 2,000 IU per day) will not do too much harm. The best way to get vitamin D substrate, as far as I can tell, is to take about 1,000 IU of vitamin D3 per every 25 pounds of body weight in the winter and stop all vitamin D in the summer and sunbathe. Alternatively, use a tanning bed when the sun is to low on the horizon to sunbathe. Remember, when you are outside, if your shadow is longer than you are, you are not making any vitamin D.
Below are passages from our paper, the heart of the reasoning the 16 experts used to issue the warning about vitamin A and cod liver oil, that is, the words in italics below are the advice of the 16 experts listed above, not just me:
"Although activated vitamin D and vitamin A signal through common cofactors, they compete for each others function. Retinoic acid antagonizes the action of vitamin D and its active metabolite. In humans, even the vitamin A in a single serving of liver impairs vitamin Ds rapid intestinal calcium response. In a dietary intake study, Oh et al found that a high retinol intake completely thwarted vitamin Ds otherwise protective effect on distal colorectal adenoma, and they found a clear relationship between vitamin D and vitamin A intakes, as the women in the highest quintile of vitamin D intake also ingested around 10,000 IU/d of retinol.
Furthermore, the consumption of preformed retinol even in amounts consumed by many Americans in both multivitamins and cod liver oil may cause bone toxicity in individuals with inadequate vitamin D status. Women in the highest quintile of total vitamin A intake have a 1.5-times elevated risk of hip fracture.
Indeed, a recent Cochrane Review found that vitamin A supplements increased total mortality rate by 16%, perhaps through antagonism of vitamin D.
Another recent Cochrane meta-analysis concluded that although vitamin A significantly reduced the incidence of acute lower respiratory tract infections in children with low intake of retinol, as occurs in the Third World, it appears to increase the risk and/or worsen the clinical course in children in developed countries.
As early as 1933, Alfred Hess, who discovered that sunlight both prevented and cured rickets (this 1921 paper is also free) warned about vitamin A consumption, concluding, ...as to a requirement of thousands of units of vitamin A daily, the unquestionable answer is that this constitutes therapeutic absurdity, which, happily, will prove to be only a passing fad.(p 662)
Hess AF, Lewis JM, Barenberg LH. Does our dietary require vitamin A supplement? JAMA. 1933;101:657-663.
Unfortunately, Hesss prophecy of a passing fad proved premature and Americans continue consuming multivitamins and/or cod liver oil containing small amounts of vitamin D but undesirable quantities of vitamin A. For example, multivitamins, until recently, had small amounts of vitamin D (200 to 400 IU) but high amounts of preformed retinol (5,000 to 10,000 IU). This pales in comparison to a tablespoon of modern cod liver oil, most of which contains sub-physiological amounts of vitamin D (400 to 1200 IU) but supra-physiological amounts of completely preformed retinol (5,000 to 15,000 IU or, in some cases, 30,000 IU).
Clinical lore holds that Vitamin A is an anti-infective. We suggest that lore exists because of old cod liver oil studies. Semba reviewed early literature on vitamin A, usually given as cod or halibut liver oil, as a successful anti-infective. For reasons that are not entirely clear, fish liver oils of the time contained much higher amounts of vitamin D then does modern cod liver oil, perhaps because modern processing removes the vitamin D during distillation and then replace it at lower doses. Furthermore, a meta-analysis concluded that vitamin A, when given alone, increases the incidence of respiratory tract infections. If vitamin A increases the risk of respiratory infections, its high content in modern cod liver oils will only mask the full benefit of adequate vitamin D nutrition.
As the prevalence of vitamin A deficiency in the United States is apparently much lower than the prevalence of subclinical vitamin A toxicity, we cannot recommend cod liver oil for either adults or children. (We exclude fish body oil from our warning, as it contains no vitamin A or vitamin D but is a very important source of omega-3 fatty acids.) For example, in a recent assessment of serum retinyl esters in a group of obese individuals, four percent had levels >10% of total retinol which usually indicates hypervitaminosis A. Instead, a diet rich in carrots, sweet potatoes, cantaloupe, and other orange fruits and vegetables will supply all the carotenoids the body needs to make retinol without the potential for hypervitaminosis A, especially when additional preformed retinol already exists in dairy products, eggs, and fortified cereal. We wish our diet were as rich in vitamin D. With the exception of infants on formula or toddlers drinking large amounts of milk or fortified juice, adequate amounts of vitamin D are virtually impossible to obtain from diet."
Tanumihardjo SA. Food-based approaches for ensuring adequate vitamin A nutrition. Comp Rev Food Sci Food Safety. In press.
And so ends the excerpt from the 16 experts. Long story short, don't take cod liver oil or vitamin A as a retinol. Below, I add some evidence that I did not include in the paper
Dear Dr. Cannell:
A friend of mine told me vitamin A hurt his liver. Is that possible?
Jason, New York
Dear Jason:
Not only is it possible, it may be common. When patients present to their doctor with abnormal liver function tests or overt liver disease, and many hundreds of thousands do every year, how many physicians inquire about vitamin A or cod liver oil supplements? The authors below found 41 cases and warned that "chronic vitamin A consumption might represent an appreciable cause of chronic liver disease."
Geubel AP, De Galocsy C, Alves N, Rahier J, Dive C. Liver damage caused by therapeutic vitamin A administration: estimate of dose-related toxicity in 41 cases. Gastroenterology. 1991 Jun;100(6):1701-9.
If you think these 41 cases are the only ones reported, think again. Below is a link to a PubMed search showing dozens of reports that vitamin A supplements cause liver disease.
PubMed search for vitamin A toxicity causing liver disease
If you know anyone taking cod liver oil or vitamin A, advise them to stop it and have a "liver panel" blood test. It may be that abnormal liver function tests are the most sensitive indicator of vitamin A toxicity. I don't know how long it takes for toxic amounts of vitamin A to clear from the liver.
Dear Dr. Cannell:
I took cod liver oil during my pregnancy and everything went fine except a little high blood pressure but that would have been worse except for the omega-3 oils in cod liver oil. Why don't you read about cod liver oil on the Weston Price Foundation's website.
Joanne, Pennsylvania
Dear Joanne:
Women who took cod liver oil during pregnancy were five times more likely to develop hypertension during their pregnancy. The authors attempted to control for intakes of vitamins A and D but the cod liver oil the women took contained about 10,000 IU of vitamin A and only 800 IU of vitamin D. By the way, the paper reports that the vitamin A content of Icelandic cod liver oil was reduced five fold in 2006, from 8,000 to 1,200 IU per 10 cc, mainly due to the literature showing vitamin A causes birth defects.
Dear Dr. Cannell:
Are you saying no vitamin A at all or just not too much of a good thing?
John, California
Dear John:
No extra vitamin A unless you have a bowel disease that impairs absorption of vegetables and transportation of carotenoids. The paper below discusses how Americans are getting too much of a good thing. Vitamin A is like vitamin D, it has a U shaped curve, too much or too little will harm you. Too much is the rule, not too little, in developed countries. Furthermore, it gives a mechanism by which excessive doses of vitamin A will impair brain development and, although I can't put my finger on the reference right now, at least one author has proposed that excessive vitamin A intake may worsen autism. The vitamin D theory of autism would predict just that.
Dear Dr. Cannell:
I am six months pregnant and I took cod liver oil up until now. Will my baby be deformed?
Jill, Oregon
Dear Jill:
While I don't know how much cod liver oil you took, or the brand, the chances are overwhelming that your baby will be just fine. Three well-conducted case controlled trials showed excessive vitamin A leads to birth defects. Below is another article you can download for free thanks to the NEJM and get the other two references from the downloaded paper if you are interested. But don't be alarmed Jill, the vast majority of women taking vitamin A had normal babies.
Rothman KJ, Moore LL, Singer MR, Nguyen US, Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. N Engl J Med. 1995 Nov 23;333(21):1369-73.
Also, when people tell me they take cod liver oil, I have no way of knowing what they actually taking, in terms of vitamin A and vitamin D, as different cod liver oil brands have such widely varying amounts of both vitamins.
Dear Dr. Cannell:
I am a nutritionist and a member of the Weston Price Foundation. You forget that humans no longer consume the liver of all animals and fish as we have throughout history. Second, our ability to convert the beta-carotene from plants into the required animal form of vitamin A has been shown to vary from poor to nonexistent.
Joe, New Mexico
Dear Joe:
The idea that the human genome evolved eating liver is absurd. By the time humans could hunt large mammals, the genome had already evolved. Humans evolved eating a diet not dissimilar to the Great Apes, vegetables, fruit, roots, and some bugs. As far as us eating all kinds of liver, have you tried polar bear liver lately? Or sled dog liver? One serving can be fatal. There is evidence that later humans, when they learned to bring down large mammals, suffered vitamin A toxicity, probably from the liver they began consuming. Chronic consumption of chicken liver caused vitamin A toxicity in twin girls.
Secondly, the idea that the natural system God created to regulate vitamin A levels is malfunctioning in almost everyone (our intestinal system that converts carotenoids into vitamin A as we need it) is simply silly. The studies you are referring to are from developing countries where chronic malabsorption and diarrheal diseases are endemic. Just because an autistic child has "bowel problems, it does not mean he is vitamin A deficient. Also, how many case reports of vitamin A deficiency has anyone found in American vegetarians? Plenty of iron and B12 and vitamin D deficiencies in vegans but virtually no vitamin A deficiency although many vegetarians have no preformed vitamin A intake at all, only carotenoids.
I admired everyone I met at the Weston Price Foundation when I spoke there several years ago, mainly because of their commitment to healthy soil. However, when I brought up toxicity of cod liver oil, the atmosphere quickly turned from science to religion. Not only did I warn them about cod liver oil, the vitamin A researcher they flew in, Dr. Noel Solomon, also warned them about cod liver oil. No use. With every word either of us spoke, the flasks flashed as members of the audience took swigs of their cod liver oil .
John Cannell, MD
12/1/08The Vitamin D Council
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Croft Woodruff PhD
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