ΓΕΙΩΣΗ (EARTHING-GROUNDING)ΤΟ ΝΤΟΚΥΜΑΝΤΕΡ
Λεπτομερής ανάλυση και ανάδειξη των οφελών από την φυσική αλλά και την ''τεχνητή''γείωση.
ΓΑΛΑ ΤΟ ΘΑΝΑΤΗΦΟΡΟ ΔΗΛΗΤΗΡΙΟ
Η αλήθεια για τον καρκίνο-Gerson diet
Δείτε το βίντεο στο youtube: http://www.youtube.com/watch?v=Ye4N8EH3dog . Για να το κατεβάσετε ως torrent: http://thepiratebay.org/torrent/4830623/The_Beautiful_Truth_%282008%29_Gerson_Cancer_Therapy .
AM I TOXIC WITH HEAVY METALS?
In my last email I explained the nasty health effects of heavy metals. One of the questions that remained unanswered was "how do you know whether you or your loved ones have heavy metals in your body?"
Urine provocation tests are a ‘snap-shot’ of how the body eliminates toxic metals at any one point in time. There is usually a comparison between an initial baseline sample of urine before the chelation agent is taken, then followed by another sample after the chemical agent is taken. If the post-test shows a percentage increase in metals, then this is an indication that there are metals stored in the body tissues and organs.
It does not, however, give information on the total load of the body, nor is one provocation test comparable with another one repeated 3 months down the line. It simply means that if metals are still being eliminated after provocation with the chelating agent, then there are metals stored in the body. It really gives us no more information than this.
If the detoxification organs are compromised, as is often the case with autistic spectrum disorders, then there may be very few metals actually eliminated after provocation. What does this tell us? Can we conclude categorically that there are no metals stored in the body tissues and organs? Or few metals, or a moderate amount? How does this help us make clinical decisions?
What do we tell the patient – that today they have 3 ppm of mercury on the urine test after provocation and in 3 months time they have 2.5 ppm. Does this mean that they have eliminated 0.5ppm of mercury in total and still have 2.5 ppm left? Obviously not, as these are arbituary figures only.
Moreover, if the patient shows no percentage increase in metals in the post-provocation test, does this mean that they will not begin taking any chelating protocol as they do not need it? Could it be that the patient has compromised detoxification organs and is not eliminating or that there are metals stored deep in the tissues? This decision based on these urine tests warrants considerable caution as an extremely toxic and ill person could end up getting a lot worse if left without a chelation protocol.
Basically, the only valid conclusion that we can really make when the level of toxic metals is higher on the post-test compared to baseline, is that there are metals stored in the body tissues and organs – there is no way that we can know the total load of the body.
Hair Tissue Mineral Analysis is a better test. What are we measuring from hair and why? When the body has toxic metals circulating in the blood, the first thing that it tries to do is remove them from circulation as they are prone to do a lot of damage to different cells of the body through their vicious free radical activity. The first place that the body stores these metals is in the inert tissues such as hair and nails. When these storage sites are full, then it will start distributing and storing in other less inert tissues and organs such as fat, liver, kidneys, thyroid, brain and other organs.
At the laboratory the hair sample is dissolved in acid, where the metals and minerals are released and we are able to measure these accurately to parts per billion levels using an Inductively Coupled Plasma Mass Spectrometer (ICP-MS).
The hair sample taken indicates the metabolic activity of the body during the last two months - it is a ‘history’ of what has been circulating in the blood and not simply a snap-shot like blood and urine. We usually cut about 2 inches (5 cm) of hair, which takes about two months to grow. Therefore, the levels of metals in the hair correlate quite well with the levels in circulating blood over a two-month period – if there are no metals circulating in the blood during the last two months, then they probably will not appear in the hair at all.
The hair test really reflects the metabolic activity of the body during the last two months which is more meaningful than a snap-shot picture from blood or urine.
Zero levels of toxic metals in a hair analysis does not mean that there are zero metals stored in the body! The Hair Tissue Mineral Analysis is distinctly measuring the amount of metals that have been circulating in the blood the last couple of months, but does not tell us much about how many metals are stored in the body tissues and organs.
Thankfully there are now natural chelators that can help to eliminate these heavy metals from the body safely and gently - one that we recommend and that we will review in more detail later is called HMD.
Urine provocation tests are a ‘snap-shot’ of how the body eliminates toxic metals at any one point in time. There is usually a comparison between an initial baseline sample of urine before the chelation agent is taken, then followed by another sample after the chemical agent is taken. If the post-test shows a percentage increase in metals, then this is an indication that there are metals stored in the body tissues and organs.
It does not, however, give information on the total load of the body, nor is one provocation test comparable with another one repeated 3 months down the line. It simply means that if metals are still being eliminated after provocation with the chelating agent, then there are metals stored in the body. It really gives us no more information than this.
If the detoxification organs are compromised, as is often the case with autistic spectrum disorders, then there may be very few metals actually eliminated after provocation. What does this tell us? Can we conclude categorically that there are no metals stored in the body tissues and organs? Or few metals, or a moderate amount? How does this help us make clinical decisions?
What do we tell the patient – that today they have 3 ppm of mercury on the urine test after provocation and in 3 months time they have 2.5 ppm. Does this mean that they have eliminated 0.5ppm of mercury in total and still have 2.5 ppm left? Obviously not, as these are arbituary figures only.
Moreover, if the patient shows no percentage increase in metals in the post-provocation test, does this mean that they will not begin taking any chelating protocol as they do not need it? Could it be that the patient has compromised detoxification organs and is not eliminating or that there are metals stored deep in the tissues? This decision based on these urine tests warrants considerable caution as an extremely toxic and ill person could end up getting a lot worse if left without a chelation protocol.
Basically, the only valid conclusion that we can really make when the level of toxic metals is higher on the post-test compared to baseline, is that there are metals stored in the body tissues and organs – there is no way that we can know the total load of the body.
Hair Tissue Mineral Analysis is a better test. What are we measuring from hair and why? When the body has toxic metals circulating in the blood, the first thing that it tries to do is remove them from circulation as they are prone to do a lot of damage to different cells of the body through their vicious free radical activity. The first place that the body stores these metals is in the inert tissues such as hair and nails. When these storage sites are full, then it will start distributing and storing in other less inert tissues and organs such as fat, liver, kidneys, thyroid, brain and other organs.
At the laboratory the hair sample is dissolved in acid, where the metals and minerals are released and we are able to measure these accurately to parts per billion levels using an Inductively Coupled Plasma Mass Spectrometer (ICP-MS).
The hair sample taken indicates the metabolic activity of the body during the last two months - it is a ‘history’ of what has been circulating in the blood and not simply a snap-shot like blood and urine. We usually cut about 2 inches (5 cm) of hair, which takes about two months to grow. Therefore, the levels of metals in the hair correlate quite well with the levels in circulating blood over a two-month period – if there are no metals circulating in the blood during the last two months, then they probably will not appear in the hair at all.
The hair test really reflects the metabolic activity of the body during the last two months which is more meaningful than a snap-shot picture from blood or urine.
Zero levels of toxic metals in a hair analysis does not mean that there are zero metals stored in the body! The Hair Tissue Mineral Analysis is distinctly measuring the amount of metals that have been circulating in the blood the last couple of months, but does not tell us much about how many metals are stored in the body tissues and organs.
Thankfully there are now natural chelators that can help to eliminate these heavy metals from the body safely and gently - one that we recommend and that we will review in more detail later is called HMD.
Successfully Treating Schizophrenia With Niacin (Abram Hoffer)
Codex Alimentarius
Vitamin C Saves Lives
Vitamin C Saves Lives!
After Linus Pauling wrote his book on vitamin C in 1970, mortality from heart disease decreased 30-40% in the USA. From around 741,000 deaths per year to less than 500,000 deaths by 1986 - U. S. Bureau of National Health Statistics 1986.
Yet, Vitamin C Attacks Continue. . .
BLOWING SMOKE
Sun Aug 12 10:17:52 CDT 2001
The continued stream of unfounded attacks generated massive worldwide news, usually before any published article is available for inspection, review or comment.
The latest (Aug 8th) attack blames vitamin C and vitamin E for "interfering" with statin anti-cholesterol drugs" and advises "cardiovascular patients not to take antioxidants." In our opinion, this is DEADLY advice, and we devote this PAGE to a discussion. As you blithely take your cholesterol lowering medication, keep this recent coincidental FDA action in mind: Statin Cholesterol Lowering Drug Recalled Due to Deaths
Who Are These Guys? Who Has the Power to Repeatedly Plant Fake Worldwide News Stories?
(The three most recent prior attacks were unfounded. They were either retracted or never published.) Remember, animals generally make large (multiple gram) amounts of vitamin C daily. They do not suffer any known DNA damage. These stories are based in simple economics, not rigorous science. Vitamin C leads to health and poses an economic threat to pharmaceutical-based medicine. - O. Fonorow
Who is behind these attacks
Even Linus Pauling Institute Attacks Vitamin C!
"The vast majority of all published studies on vitamin C supplementation show an overwhelmingly positive effect on health," said Phil Harvey, Ph.D.,
Yet again we are faced with a major media attack before any paper is published. These reports are usually based on some minor scientific finding, they are not fabrications, per se, but they are taken out of context and widely reported without having been published in a peer reviewed Journal. And according to Ralph Moss in his book Antioxidants Against Cancer, Page 45, retractions are not published:
"What I find particularly astonishing is that later in 1998, the authors of the original [widely reported] study published another report on vitamin C. This showed that people who received 500 milligrams of vitamin C per day had substantial benefit from the practice!
"These results illustrate... a role for vitamin C in the regulation of DNA repair enzymes," and demonstrate an "antioxidant effect," they wrote.
"Did you hear about these pro-vitamin C results? Probably not, because unlike the scare stories, these positive findings and comments passed without mention in the mainstread media.
- Ralph Moss
As the threat to the economic well being of Medicine and major Pharmaceutical companies (from vitamin C) increases, so do the groundless attacks designed to scare people from taking Vitamin C. (And according to published statistics - these attacks work. Vitamin C sales are off 19% year over year.)
If you doubt the impact of vitamin C on pharmaceutical profits, consider that after Linus Pauling wrote his book on vitamin C in 1970, mortality from heart disease decreased 30-40% in the USA. From around 741,000 deaths per year (National Center for Health Statistics, Pauling 86, p 164) to less than 500,000 deaths per year. Adam Smith's Invisible Hand works against us when it works for medicine without ethics. Fewer people with heart disease means enormous economic loss for the segments of our society that make money from heart disease.
Vitamin C Foundation
I've already figured out what is wrong with the researcher's work, and I'm a rank amateur at this.
The researcher dropped vitamin C into lipid hyperoxide to see if it would produce genotoxic materials.
Lipid hyperoxide is formed by free radical damage on lipids.
People who take vitamin C DO NOT FORM lipid hyperoxide because vitamin C is a free-radical scavenger.
In addition, lipid hyperoxide does a huge amount of bodily damage itself (such as heart disease plaques, I believe), and anything that combines with it would, under normal circumstances, be considered a good thing.
Thus what this researcher did was to take a reaction out of context using a scenario that cannot occur, and blamed vitamin C for forming potentially harmful compounds from a particularly nasty one. Typical bogus research.
Jon Campbell
Can you imagine how Science mag. would have responded if the said test-tube experiment had produced a group of anti-cancer, tumor-inhibiting compounds? Of course, they would have said "this needs further study and corroboration with animal or clinical tests before we can publish such a claim". Since the claim goes against Vitamin C, they put out the red carpet. It really is a transparent lie they have woven, fully understandable when you consider that 50% of the pages of Science mag. are composed of advertisements for the bio-tech and pharm industry. Reminds me when they were issuing all sorts of articles "proving" how save and efficient nuclear energy was.
James DeMeo, Ph.D.
Filed: 11/07/2001) Health.telegraph.co.uk
Dr Sarah Brewer on worries about too much vitamin C
DEAR DOCTOR - I take vitamin C and was alarmed by the recent sugg estions that high dose vitamin C might cause cancer. What is your opinion?
One of the authors of the recent paper in Science was so worried that his results would be misreported that he was quoted as saying: "Absolutely, for God's sake, don't say vitamin C causes cancer". Unfortunately, many reports did. The study used vitamin C to induce conversion of lipid hydroperoxides (which are formed in the body during the oxidation of unsaturated fats) into compounds that can damage DNA. This effect, demonstrated artificially in a test tube, cannot occur in living cells where a number of enzyme systems exist to remove the damaging substances formed. In addition, fat-soluble Vitamin E protects lipid cell membranes in living systems from oxidative reactions and, as vitamin C is essential for the regeneration of vitamin E, it actually plays an important role in preventing the formation of lipid hydroperoxides.
Other factors that make this a non-story include the fact that researchers used lipid hydroperoxide concentrations 10,000 times greater than those found in the body, and that the methods used to measure DNA could have caused the damage noted. There is ample evidence that vitamin C is beneficial in doses of up to 2g daily. A recent study of 19,196 adults aged 45 to 79 in Britain found that circulating levels of vitamin C were inversely related to death from all causes over the four-year study period. While diet should always come first, I will continue to take my supplements.
Knowledge of Health, Inc.
457 West Allen Avenue #117 San Dimas, California 91773
Telephone: 909.861.3454 Fax: 909.861.3442 Email: [email protected]
For Immediate Release 6.16.2001 Contact: Bill Sardi 909.861.3454
NEWS MEDIA AND TEST-TUBE
RESEARCHERS OVERLOOKED
FAVORABLE HUMAN STUDIES
ON VITAMIN C
SAN DIMAS, CA - Researchers at the University of Pennsylvania Center for Cancer Pharmacology and the news media overlooked five separate human studies that disproved high-dose vitamin C causes DNA damage and instead chose to make headlines out of a sole test-tube study that concluded that a 200-milligram dose of vitamin C could potentially cause cancer.
While millions of Americans who take vitamin C supplements were beginning to question whether high-dose vitamin C is safe, Ian A. Blair, the lead researcher in the study published in June 15 issue of Science magazine, was unavailable for comment and is travelling outside the country, leaving an air of uncertainty in the public's mind regarding vitamin C.
Usually test-tube studies precede animal or human studies, and results in the laboratory often do not coincide with those found in living systems. In this case, human studies had already been performed and have, as expected, not confirmed the notion that vitamin C is toxic to living cells or DNA.
Even though researchers are a bit puzzled as to why vitamin C supplements do not always reduce the risk for cancer, there are no studies that confirm that vitamin C supplement users are at greater risk for cancer.
Report overlooked contrary data
The report in Science was submitted in early February and approved for publication in May of 2001, and included other published references dated as late as the year 2000. Four of the five human studies that do not confirm that vitamin C causes DNA damage were published in 2000, and could have been cited by the authors of the report in Science, but were overlooked.
The five overlooked studies
For example, researchers at Johns Hopkins University could not find evidence of a "significant main effect or interaction effect on oxidative DNA damage in non-smoking adults" with 500 milligrams/day of vitamin C supplementation. [Cancer Epidemiology Biomarkers Prevention 2000 July;9:647-52]
Another study, conducted by researchers in Germany found that 1000 mg. of vitamin C consumed by smokers and non-smokers for 7 days did not produce DNA damage as measured by the number of micronuclei in blood lymphocytes. [Free Radical Research 2001 March;34:209-19]
In yet another study conducted by Immunosciences Laboratory in California, twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. This study concluded that "ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on natural killer cell activity, apoptosis, or cell cycle." [Cancer Detection Prevention 2000;24: 508-23]
In London researchers measured the effects of 260 milligrams/day of vitamin C and vitamin C + iron in humans and concluded that there was "no compelling evidence for a pro-oxidant effect of ascorbate supple- mentation, in the presence or absence of iron, on DNA base damage." [Biochemistry Biophysical Research Communications 2000 November 2;277:535-40]
In Ireland, researchers gave 1000 mg. of vitamin C to volunteers for 42 days and concluded that "supplementation with vitamin C decreased significantly hydrogen-peroxide-induced DNA damage in peripheral blood lymphocytes." [British Journal Nutrition 2000 August;84:195-202]
News media also remiss
The news media was also remiss in not checking whether there was any contrary data on this topic, and did not interview other scientific sources, such as the Linus Pauling Foundation, the Vitamin C Foundation, the National Nutritional Foods Association or the Council for Responsible Nutrition. Reuters Health and the Associated Press health reporters ran the story without checking on the validity of the report in Science. No explanation has been given for this oversight, even though science reporters for both organizations are well versed on medical topics. A cub reporter could have uncovered the five contrary human studies in a 30-minute search on Medline.
Similar erroneous report in 1998
Recently researchers have been exploring the dual nature of vitamin C. Is vitamin C a pro-oxidant or rusting agent, or is it an antioxidant, a cellular preservative? In 1998 Nature Magazine published a similar report to the University of Pennsylvania study. Researchers then claimed that high-dose vitamin C had "rusting" properties in living cells and that 500 milligrams of vitamin C was found to oxidize guanine, one of the four bases that make up DNA. But the researchers overlooked that high-dose vitamin C also increased the level of guanine, another of the nucleic acids in DNA. The researchers failed to point out their paradoxical results and the news media made headlines out of the story then, as they are doing now. No corrections were ever published. The mistaken impression left on the public then was that high-dose vitamin C is potentially dangerous.
It remains unclear whether the researchers at the University of Pennsylvania Center for Cancer Pharmacology will clear the air on their report, which received worldwide headlines. ####
June 14, 2001
TO: Will Dunham, health reporter for
REUTERS, Washington DC
[email protected]
FROM: Bill Sardi
Knowledge of Health, Inc.
Independent health journalist
Diamond Bar, California
[email protected]
I have questions regarding your recent report which alleges that vitamin C supplements beyond 200 milligrams per day may promote DNA damage that could cause cancer.
1. Were you aware this is not a new story, and that researchers can create DNA damage in test tubes, but not in living systems, with many essential nutrients or food factors found in the diet?
2. Why didn't your report carry interviews with those who have a differing opinion? Interviews could have been conducted with the Vitamin C Foundation, or the National Nutritional Foods Assn., or the Council for Responsible Nutrition? Did you seek to obtain balanced information?
3. Why did Reuters select this report from Science Magazine, and why did it run with the headlines "Vitamin C Found To Promote Cancer-Causing Agents?" rather than "Researchers study dual role of vitamin C in cancer???"
4. What do you think the impact of your report will be on the public at large, since many people take vitamin C supplements in doses that exceed what your article suggests as safe?
5. Are you aware of reports which show that consumption of vitamin C beyond 300 milligrams per day causes a major reduction in the risk of cataracts, and beyond 500 milligrams per day reduces the risk of hypertension? These dosages would generally required supplements rather than foods.
6. Are you aware that, in July of 2000, researchers found that supplementation of diet with vitamin C (500 mg/day) had no significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in nonsmoking adults. [Cancer Epidemiol Biomarkers Prev 2000 Jul;9(7):647-52] In other words, high-dose vitamin C did not produce any measurable DNA damage.
The very issue of whether vitamin C promotes DNA damage was undertaken in 1998 by researchers at the International Antioxidant Research Centre, Department of Pharmacology, King's College, London, United Kingdom. [Biochem Biophys Res Commun 1998 May 8;246(1):293-8] They reported on the effects of co-supplementing healthy volunteers with iron (14 mg/day ferrous sulphate) and vitamin C (either 60 mg/day or 260 mg/day as ascorbic acid) on levels of oxidative DNA damage in white blood cells. The subjects were divided into two groups: one group of 20 volunteers with a higher mean initial level of plasma vitamin C (71.9 +/- 14.0 mumol/l) and a second group of 18 volunteers with a lower mean level (50.4 +/- 25.8 mumol/l). In the first group there was a significant rise in several oxidative DNA base damage products and in total oxidative DNA damage in DNA extracted from white blood cells, but not in 8-hydroxyguanine, after 6 weeks of supplementation. However, after 12 weeks levels returned approximately to normal. In the group with the lower initial level of plasma ascorbate, presupplemental levels of oxidative DNA damage were higher and decreased on supplementation with iron and ascorbate.
A recent study, reported in the January issue of Cancer Epidemiology Biomarkers, indicates, among 711,891 men and women in the United States, followed from 1982 thru 1996, regular use of vitamin C supplements, even long-term use, was not associated with colorectal cancer mortality. The combined-sex rate ratios were 0.89 for 10 or more years of vitamin C use, a slight reduction in the risk for cancer. In subgroup analyses, use of vitamin C supplements for 10 or more years was associated with decreased risk of colorectal cancer mortality before age 65 years, 52% relative reduced risk, and 60% reduced risk reduced risk for rectal cancer mortality. [Cancer Epidemiol Biomarkers Prev 2001 Jan;10(1):17-23]
In India researchers used high-dose vitamin C in animals exposed to cigarette smoke and found that vitamin C supplementation increased resistance to lipid peroxidation and "this study seems to suggest that an intake of a mega dose of vitamin C can protect the liver from oxidant damage caused by cigarette smoke." [J Appl Toxicol 1997 Sep-Oct;17(5):289-95]
In 1999 researchers at the Fred Hutchinson Cancer Research Center in Seattle reported that supplement use in 697 incident prostate cancer cases (ages 40-64) identified from the Puget Sound Surveillance, Epidemiology and End Results program registry. Adjusted odds ratios vitamin C, 0.77 (range 0.57 - 1.04), about a 23% relative reduced risk. The researchers said: "Overall, these results suggest that multivitamin use is not associated with prostate cancer risk." [Cancer Epidemiol Biomarkers Prev 1999 Oct;8(10):887-92]
Any cub reporter could have found these reports in just 30 minutes on Medline. Why weren't reports like these incorporated into your report? In light of these scientific studies, would you call your report fair and balanced?
Shame on the Linus Pauling Institute
The latest attack quotes so-called authorities at the Linus Pauling Institute. If these quotes are accurate, the institute now uses Pauling's name, but lacks his spirit. Dr. Frei has not read Pauling's HOW TO LIVE LONGER AND FEEL BETTER, else he would not make such inaccurate statements using Pauling's name. We would ask any contributor to check with the Pauling Institute, re-read HOW TO LIVE LONGER AND FEEL BETTER, and reconsider giving the institute any more money until Dr. Frei leaves his post.
REUTERS NEWS REPORT Thursday June 14 3:11 PM ET
Vitamin C Found to Promote Cancer-Causing Agents
By Will Dunham
WASHINGTON (Reuters) - Vitamin C, an essential nutrient found in fruits and
vegetables and taken in large doses by many people as a dietary supplement,
is a double-edged sword, providing benefits but also inducing the production
of compounds associated with cancer, researchers said on Thursday.
Researchers at the University of Pennsylvania added vitamin C, also known as
ascorbic acid, to solutions of a degraded version of an important fatty acid
found in blood, and found that it triggered the production of DNA-damaging
agents known to cause mutations associated with a variety of cancers.Lead
researcher Ian Blair of the university's Center for Cancer Pharmacology
cautioned that the study was conducted in a test tube and not with living
human cells or in actual people.
``Absolutely for God's sake don't say vitamin C causes cancer,'' Blair said
in a telephone interview.``
The key finding is that vitamin C can do good things and bad things. And
we've figured out what the bad ones are. In terms of the impact, I think it
just redirects people's attention to the fact that you can't replace a good
diet with magic bullets such as vitamin C.''The value of vitamin C has been
the subject of a long and heated debate in the scientific community. One of
the leading scientists of the 20th century, Linus Pauling, who died at age 93
in 1994, championed it as a tool for fighting cancer.But skeptics argued that
numerous studies have found that vitamin C produced no benefit in combating
cancer, and that taking supplements actually could have negative
consequences. The new study appears to add weight to those concerns.
CAUTION URGED ON DIETARY SUPPLEMENTS
``Far more caution should be taken in the use of dietary supplements -- and
an insistence on real proof that there's a benefit before undertaking any of
them,'' said Dr. Arthur Grollman, director of the Laboratory for Chemical
Biology at the State University of New York at Stony Brook.``The real,
serious implication is that it (vitamin C) could contribute to DNA damage
that could cause cancer,'' added Grollman, an expert in cancer causes who was
not involved in the study. ``It just adds more evidence that there could be a
significant risk to ascorbic acid.''Blair said the study, which appears in
the journal Science, may explain why vitamin C has shown little effectiveness
at preventing cancer in clinical trials.
Vitamin C is a water-soluble vitamin that is important for bone and
connective tissue growth, wound repair and the function of blood vessels. It
is abundant in citrus fruits, green peppers, tomatoes, cabbage and potatoes.
The recommended U.S. adult dietary allowance for vitamin C is 60 milligrams
daily. Most supplements contain many times that amount.Dr. Garret FitzGerald,
director of the University of Pennsylvania's Center for Experimental
Therapeutics, pointed to evidence of a benefit from an overall healthy diet
rather than taking supplements on any particular nutrient.``We have very
clear evidence that eating a diet rich in vegetables and fruits is a healthy
thing in terms of it being associated with a reduced incidence of cancer and,
indeed, heart disease, for that matter,'' FitzGerald said.
``On the one hand, I would say to people there's no evidence to stop taking
vitamin C on the basis of these observations at this point in time. On the
other hand, I'd say consider very carefully what the evidence is for taking
vitamin C, which is nonexistent. The better part of valor is: save your
money.''
VITAMIN C IS AN ANTIOXIDANT
Vitamin C acts as an antioxidant protecting against damage by ``free radicals'' -- highly reactive ions produced by the breakdown of oxygen in cells. In addition to damaging DNA directly, free radicals also can act indirectly.They begin by converting linoleic acid, the major polyunsaturated fatty acid in human blood plasma and the key polyunsaturated fatty acid in certain cooking oils, into another compound called a lipid hydroperoxide.When certain metal ions are present as catalysts, the compound degrades into DNA-damaging agents called genotoxins, which cause mutations that have been found in human tumors. Blair said he had a hunch that vitamin C might be capable of changing lipid hydroperoxides into genotoxins. He added vitamin C to test tube solutions of lipid hydroperoxides, using concentrations comparable to those found in the human body if a person were taking 200 milligrams a day.The study found that vitamin C was more than twice as efficient as transition metal ions at inducing the formation of genotoxins, including a particularly potent variety.
Read About the Role of Vitamin C in Heart Disease
Knowledge of Health, Inc.
457 West Allen #117 San Dimas, California 91773
Phone: 909.861.3454 Fax: 909.861.3442 E-mail: [email protected]
For Immediate Release Contact: Bill Sardi 909.861.3454
Who is Behind The Negative News Reports On Vitamin C?
The news media features a report published in Science magazine that high-dose vitamin C in a test-tube causes DNA damage that could lead to cancer. It's not news, since test-tube studies do not correlate with tests conducted in living systems and the dual role of vitamin C as both a pro-oxidant (rusting agent) and anti-oxidant (cell preservative) has been published in scientific journals for some time now. But it's a heralded news story that Reuters Health and the Associated Press embellish with sensational headlines. Instead of saying "Dual nature of vitamin C in cancer explored," the headlines read "Vitamin C Found to Promote Cancer- Causing Agents." It's yellow journalist at its worst, since a quick search on Medline reveals that high-dose vitamin C did not reveal any toxic by-products in human studies. The toxic effect is only observed in test tubes.
The lead university researcher, Ian Blair of the University of Pennsylvania Center for Cancer Pharmacology, is conveniently outside the country, so he can't easily respond to questions. Ian Blair, covers his story by saying "Absolutely, for God's sake, don't say vitamin C causes cancer." But the headlines read otherwise.
The University of Pennsylvania is the originator of Oncolink, a prestigious online resource of cancer information. But who sponsors Oncolink? Hidden behind the whole affair are Oncolink's sponsors --- the pharmaceutical companies. AstraZeneca, Amgen, Ortho Biotech, Pharmacia, Pfizer and Janssen Pharmaceuticals. Are the drug companies using a major university as their shill to spread misinformation about vitamins?
It is becoming more obvious that misinformation about vitamins, minerals and herbal products is being planted in the news media and published in medical journals in a calculated fashion. The reason is that more and more Americans are taking health care into their own hands and relying less and less on doctors and drugs to cure their ills. The big secret is that the biological action of virtually every prescription drug can be duplicated with nutritional supplements at far less cost and with fewer side effects. The only way to counter the growing demand for natural remedies is to confuse the public with misinformation.
And the misinformation campaign is working. The natural products industry reports their growth has leveled off. Vitamin C sales were off by 19.2 percent last year according to a report in Natural Foods Merchandiser. In the past months dubious negative reports have been published on garlic, St. John's wort, and products containing ephedra. A characteristic of all these reports is their emphatic conclusion that all previous research which confirmed the validity of these natural remedies is to be discarded because the latest scientific report reached a contrary conclusion.
Last year the news media made a front- page headline story out of a presentation on vitamin C at the American Heart Association meeting. The study wasn't even published and hadn't undergone peer review, but the news agencies were quick to release a factitious story that high-dose vitamin C could clog arteries in the neck (the carotids). Vitamin C does not clog arteries, but it does strengthen and thicken the walls of arteries via its ability to promote collagen formation.
How do these non-news stories get front-page coverage? It's simple. Public relations agencies have bragged at seminars how they can take a presentation at a medical meeting and get it aired on television and published in newspapers. These publicity agencies do the dirty work of planting misinformation in the news media. It's propaganda, not news.
The natural products industry is mounting its own public information campaign, to counter negative news stories, and has hired their own agency, Hill & Knowlton of Washington, D.C., to air its side of the story.
There are simply no standards of journalism being upheld here. Bad science gets front-page coverage regardless of whether it is true or not. Journalists aren't checking on the validity of medical reports, and they aren't interviewing opposing views. In the case of the recent vitamin C report, reporters did not interview the National Nutritional Foods Association, the Council for Responsible Nutrition, the Vitamin C Foundation, nor the American Healthcare Products Association.
But how long can the public be fooled? Why are the pharmaceutical companies so afraid of a simple vitamin? It's because high doses of vitamin C virtually eradicate the risk of developing cataracts, eliminate the need for blood pressure medication, reduce the need for anti-allergy drugs, reduce the risk of gall stones, and produce many other health benefits. The drug companies can't invent and patent a molecule as efficacious as vitamin C. ####
Questions for Study Authors and Media
TO: Owen Fonorow
VITAMIN C FOUNDATION
FROM: Bill Sardi
I just E-mailed this inquiry to Ian A. Blair, the lead researcher of the
now infamous vitamin C report in Science Magazine.
June 15, 2001
TO: Ian A. Blair
Center for Cancer Pharmacology
University of Pennsylvania
[email protected]
FROM: Bill Sardi
Health reporters, Nutrition Science News
[email protected]
Phone: 909.861.3454
Diamond Bar, California USA
Unfortunately your paper in SCIENCE regarding ascorbic acid and DNA damage was published while you were out of the country and unavailable for quick comment. Of course, it is disappointing that the news media made such headlines out of research that does not appear to be new. The issue of whether vitamin C is a pro-oxidant or anti-oxidant has been debated for some time now. The fact that your paper concluded from a test-tube study that vitamin C concentrations equivalent to a 200 mg. dosage in humans could be genotoxic is not confirmed by epidemiological or human studies which your paper did not cite.
The submission date on your paper was February 2001, and your paper cited other references as late year 2000. The following reports, which includes reports up to the year 2000, encompassing a review of human studies with vitamin C and DNA damage, do not confirm your findings, and should have been included in your paper, am I correct?
I was wondering why your paper did not cite these references and why you did not inform the news media that your findings were not confirmed by human nor epidemiological studies? Your comments to the news media left the door open that it is possible for vitamin C to promote cancer. The references below are for your review, with the total abstracts following. Don't you think you should clear this matter up by clarifying the conclusion from your paper in light of other contrary research studies conducted outside of test tubes?
For example, researchers at Johns Hopkins University could not find evidence of a "significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in non-smoking adults" with 500 milligrams/day of vitamin C supplementation. [Cancer Epidemiol Biomarkers Prev 2000 Jul;9(7):647-52]
Another study, conducted by researchers in Germany found that 1000 mg. of vitamin C consumed by smokers and non-smokers for 7 days did not produce DNA damage as measured by the number of micronuclei in blood lymphocytes. [Free Radic Res 2001 Mar;34(3):209-19]
In yet another study conducted by Immunosciences Laboratory, twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. This study concluded that "ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle." [Cancer Detect Prev 2000;24(6):508-23]
In London researchers measured the effects of 260 milligrams/day of vitamin C and vitamin C + iron in humans and concluded that there was "no compelling evidence for a pro-oxidant effect of ascorbate supplementation, in the presence or absence of iron, on DNA base damage measured by GC-MS." [Biochem Biophys Res Commun 2000 Nov 2;277(3):535-40]
In Ireland, researchers gave 1000 mg. of vitamin C to volunteers for 42 days and concluded that "supplementation with vitamin C decreased significantly H2O2-induced DNA damage in peripheral blood lymphocytes." [Br J Nutr 2000 Aug;84(2):195-202]
I await your comment.
Cancer Epidemiol Biomarkers Prev 2000 Jul;9(7):647-52
The effects of vitamin C and vitamin E on oxidative DNA damage: results from a randomized controlled trial.
Huang HY, Helzlsouer KJ, Appel LJ.
Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205-2223, USA.
Oxidative DNA damage may be important in mutagenic, carcinogenic, and aging processes. Although it is plausible that antioxidant vitamins may reduce oxidative DNA damage, evidence from human studies has been sparse and inconsistent. We determined the short-term effects of vitamin C (500 mg/day) and vitamin E (400 IU d-alpha-tocopheryl acetate/day) supplements on oxidative DNA damage in a double-masked, placebo-controlled, 2x2 factorial trial in 184 nonsmoking adults. Mean duration of supplementation was 2 months. Oxidative DNA damage was measured by 24-h urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). At baseline, urinary 8-OHdG (mean +/- SE; ng/mg creatinine) was associated with race (15.6 +/- 0.8 in African Americans versus 20.3 +/- 1.2 in Caucasians, P = 0.001), prior antioxidant supplement use (18.6 +/- 0.8 in users versus 13.8 +/- 1.5 in non-users, P = 0.007), and regular exercise (19.2 +/- 1.1 in exercisers versus 16.6 +/- 0.9 in non-exercisers, P = 0.04). Fruit and vegetable intake and serum ascorbic acid were inversely associated with urinary 8-OHdG (P-trend = 0.02 and 0.016, respectively). The benefits of fruit and vegetable intake became evident with the consumption being at least three servings/day. At the end of supplementation, change from baseline in urinary 8-OHdG (mean +/- SE; ng/mg creatinine) was -0.6 +/- 1.4 (P = 0.61), 0.6 +/- 1.1 (P = 0.59), 0.5 +/- 1.0 (P = 0.61), and 1.6 +/- 1.4 (P = 0.27) in the placebo, vitamin C alone, vitamin E alone, and combined vitamins C and E groups, respectively. In overall and subgroup analyses, there was no significant main effect or interaction effect of the supplements on urinary 8-OHdG. In conclusion, supplementation of diet with vitamin C (500 mg/day) and vitamin E (400 IU d-alpha-tocopheryl acetate/day) had no significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in nonsmoking adults. However, several aspects of a healthy lifestyle were associated with lower oxidative DNA damage.
Free Radic Res 2001 Mar;34(3):209-19
Protective Effects of Vitamins C and E on the Number of Micronuclei in Lymphocytes in Smokers and their Role in Ascorbate Free Radical Formation in Plasma.
Schneider M, Diemer K, Engelhart K, Zankl H, Trommer WE, Biesalski HK.
Fachbereich Biologie / Abteilung Humanbiologie der Universitaet Kaiserslautern, Germany.
Cigarette smoke is widely believed to increase free radical concentrations causing subsequent oxidative processes that lead to DNA damage and hence, to several diseases including lung cancer and atherosclerosis. Vitamin C is a reducing agent that can terminate free-radical-driven oxidation by being converted to a resonance-stabilized free radical. To investigate whether short-term supplementation with the antioxidants vitamin C and E decreases free-radical-driven oxidation and thus decreases DNA damage in smokers, we determined the frequency of micronuclei in lymphocytes in 24 subjects and monitored the electron paramagnetic resonance signal of ascorbate free radical formation in plasma. Further parameters comprised sister-chromatid exchanges and thiobarbituric acid-reactive substances. Twelve smokers and twelve non-smokers took 1000 mg ascorbic acid daily for 7 days and then 1000 mg ascorbic acid and 335.5 mg RRR-alpha-tocopherol daily for the next 7 days. Baseline concentrations of both vitamins C and E were lower and baseline numbers of micronuclei were higher (p < 0.0001) in smokers than in non-smokers. After 7 days of vitamins C and E, DNA damage as monitored by the number of micronulei was decreased in both, smokers and non-smokers, but it was more decreased in smokers as indicated by fewer micronuclei in peripheral lymphocytes (p < 0.05). Concomitantly, the plasma concentrations of vitamin C (p < 0.001) as well as the ascorbate free radical (p < 0.05) were increased. The corresponding values in non-smokers, however, did not change. Our findings show that increased ascorbate free radical formation in plasma after short-term supplementation with vitamins C and E can decrease the number of micronuclei in blood lymphocytes and thus DNA damage in smokers.
Cancer Detect Prev 2000;24(6):508-23
New evidence for antioxidant properties of vitamin C
Vojdani A, Bazargan M, Vojdani E, Wright J.
Immunosciences Lab, Inc, Beverly Hills, CA 90211, USA.
This study was designed to examine the effect of 500 to 5,000 mg of ascorbic acid on DNA adducts, natural killer (NK) cell activity, programmed cell death, and cell cycle analysis of human peripheral blood leukocytes. According to our hypothesis, if ascorbic acid is a pro-oxidant, doses between 500 and 5,000 mg should enhance DNA adduct formation, decrease immune function, change the cell cycle progression, and increase the rate of apoptosis. Twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. On days 0, 1, 7, 15, and 21, blood was drawn from them, and the leukocytes were separated and examined for intracellular levels of ascorbic acid, the level of 8-hydroxyguanosine, NK cell activity, cell cycle progression, and apoptosis. Depending on the subjects, between a 0% and a 40% increase in cellular absorption of ascorbic acid was observed when daily doses of 500 mg were used. At doses greater than 500 mg, this cellular absorption was not increased further, and all doses produced equivalent increases in ascorbic acid on days 1 to 15. This increase in cellular concentration of ascorbic acid resulted in no statistically meaningful changes in the level of 8-hydroxyguanosine, increased NK cytotoxic activity, a reduced percentage of cells undergoing apoptosis, and switched cell cycle phases from S and G2/M to G0/G1. After a period of 1 week, with no placebo or vitamin washout, ascorbic acid levels along with functional assays returned to the baseline and became equivalent to placebos. In comparison with baseline values, no change (not more than daily assays variation) was seen in ascorbate concentrations or other assays during oral placebo treatment. We concluded that ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle.
Biochem Biophys Res Commun 2000 Nov 2;277(3):535-40
Potential problems of ascorbate and iron supplementation: pro-oxidant effect in vivo?
Proteggente AR, Rehman A, Halliwell B, Rice-Evans CA.
Wolfson Centre for Age-Related Diseases, GKT School of Biomedical Sciences, King's College London, St. Thomas' Street, London, SE1 9RT, United Kingdom.
The comparison was undertaken between the effects of ascorbate versus ascorbate plus iron supplementation on DNA damage. Twenty healthy subjects with initial levels of plasma ascorbate of 67.2 +/- 23.3 micromol/l were randomly assigned to and cycled through one of three supplementation regimes: placebo, 260 mg/d ascorbate, 260 mg/d ascorbate plus 14 mg/d iron for 6 weeks separated by 8-week washout periods. Supplementation did not cause a rise in total oxidative DNA damage measured by GC-MS. However, a significant decrease occurred in levels of 8-oxo-7,8-dihydroguanine by ascorbate supplementation and 5-hydroxymethyl uracil by both ascorbate and ascorbate plus iron supplementation, relative to the pre-supplemental levels but not to the placebo group. In addition, levels of 5-hydroxymethyl hydantoin and 5-hydroxy cytosine increased significantly, only relative to pre-supplementation, by ascorbate plus iron treatment. No compelling evidence for a pro-oxidant effect of ascorbate supplementation, in the presence or absence of iron, on DNA base damage was observed. Copyright 2000 Academic Press.
Br J Nutr 2000 Aug;84(2):195-202
The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes.
Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA.
Cancer and Ageing Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland.
There is a wealth of epidemiological information on antioxidants and their possible prevention of disease progression but very little of the research on antioxidants has involved intervention studies. In this study, the potential protective effect of vitamin C or E supplementation in vivo against endogenous and H2O2-induced DNA damage levels in lymphocytes was assessed. The supplementation involved fourteen healthy male and female non-smokers mean age 25-53 (SD 1.82) years, who were asked to supplement an otherwise unchanged diet with 1000 mg vitamin C daily for 42 d or 800 mg vitamin E daily for 42 d. DNA damage in H2O2-treated peripheral blood lymphocytes (PBL) and untreated PBL before and after supplementation, and during a 6-week washout period was assessed using an ELISA. At each sampling time-point, the red cell concentrate activities of superoxide dismutase, catalase and glutathione peroxidase were also determined. Supplementation with vitamin C or vitamin E decreased significantly H2O2-induced DNA damage in PBL, but had no effect on endogenous levels of DNA damage. The activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were suppressed during the supplementation period. These supplementation regimens may be used to limit the possible adverse effects of reactive oxygen species (including those produced during the course of an immune response) on lymphocytes in vivo, and so help to maintain their functional capacity.
NNFA leaves the door open to doubt, which would be enough for many consumers to reduce their dosage of vitamin C supplements. See the sentence below which says: "While it is possible that these lipids may be converted to genotoxins, which in turn may damage DNA, it is far from conclusive that this is a cancer-causing mechanism." --- Phil Harvey, NNFA director of science and quality assurance
Vitamin C Study Premature and Inconclusive
June 15, 2001
Numerous studies over the past 30 years have demonstrated a preponderance of scientific evidence about vitamin C's positive effects, including its cancer-preventing properties. A report published yesterday in the journal Science suggests vitamin C may have carcinogenic properties - a claim that has been presented in media reports as fact. This is a dangerous and questionable leap based on a single survey compared with substantial amounts of scientific literature that indicates otherwise.
"The vast majority of all published studies on vitamin C supplementation show an overwhelmingly positive effect on health," said Phil Harvey, Ph.D., NNFA's director of science and quality assurance. "Yet this study, which was performed in a test tube - not on humans, is being represented as evidence that vitamin C is potentially harmful. Even the study's lead researcher is quoted as saying, 'Absolutely, for God's sake, don't say vitamin C causes cancer.' Yet that is exactly what is occurring."
"We are extremely concerned that consumers may hear only a portion of these reports and change their vitamin C supplementation, a change that may put their health at risk because of all the demonstrable benefits of this vitamin," Harvey said.
The study, conducted at the University of Pennsylvania, involved adding vitamin C, also known as ascorbic acid, to test tubes containing solutions of fatty acids found in the blood. According to researchers, adding vitamin C triggered mutation-causing agents identified with the development of cancer.
According to the NNFA, mutations continually occur in cells and to conclude that high doses of vitamin C cause this to happen is pure speculation and reckless.
The researchers tested lipid peroxidation (lipid hydroperoxide) from dietary fat. While it is possible that these lipids may be converted to genotoxins, which in turn may damage DNA, it is far from conclusive that this is a cancer-causing mechanism. Humans have complex biochemical mechanisms to deal with lipid peroxidations and other nutrients. For instance, vitamin E protects and augments the effect of vitamin C. Because other antioxidants were not present in the laboratory tests, the synergistic effect that would normally occur in the human body was prevented.
Many previous studies and recommendations by government agencies contradict the findings of this study, including:
Research by the National Cancer Institute that supports vitamin C's beneficial effects on reducing the risk of cancer. A health claim authorized by the Food and Drug Administration that fruits and vegetables high in vitamin C can reduce the risks of some cancers. The recent recommendation by the Institute of Medicine that daily vitamin intake be increased because of its disease-prevention properties.
Evidence that vitamin C enhances the effects of certain chemotherapy drugs, reduces toxicity of chemotherapeutic agents, and may actually prevent cancer NNFA recommends that consumers eat a diet rich in fruits and vegetables and other natural sources of vitamin C and other antioxidants. In addition, NNFA recommends supplementation with vitamin C to further realize the benefits of vitamin C contained in food.
"People should not stop taking vitamin C based on the premature conclusions from a single, contradictory study," said Harvey. "The real danger here is not from vitamin C, but from sensationalized reports that will cause consumers to stop using a supplement that is clearly beneficial to their health." NNFA also recommends that members write letters to the editor of their local newspapers when stories about the study are printed. Members are free to use the text of this alert or access the press release online at www.nnfa.org/news/press_releases/index.htm.
For an in depth look at this study and research on vitamin C, please look in the April 2000 issue of NNFA Today.
Date: Mon 25 Jun 2001
Re: "Effects of Vite C are still causing a healthy debate" L.A.Times article Mon 25 June 2001
Somehow the title of your article was lost on me... did I miss something? Where exactly was the debate. You failed to interview or quote even one of the many proponents of ascorbate who advocate ascorbates in generous amounts. Where are the Ph.d.'s or M.D.'s who have been at the fore front of Vitamin C (ascorbate is the correct term) research and orthomolecular medicine's mega-dose ascorbate treatments.
Also mysteriously absent from the article was the reason humans require "C" in the first place. Where was the overview of the topic. Most folks do not realize that a genetic fault is responsible for the ascorbate deficiency in humans. Almost every mammal makes copious amounts of ascorbate in their livers, and understress and toxic environmental conditions they produce far more yet. We are talking about 5-20 grams par day.
The L.A. Times article was simply wrong about far too many things and was lacking in a baseline of knowledge as to how and why ascorbates effect human physiology. The fact that this article by Benedict Carey was missing the word "ascorbate" tells us a lot about the writer and pathetically little about the real story of ascorbate and human physiology. May I suggestto Benedict Carey (before further embarrassment) that the following sites be reviewed and understood before more articles aboutascorbates are published.
www.vitamincfoundation.org
www.cforyourself.com
www.paulingtherapy.com
Read on.
Sascha Sarnoff, Health Advocate/Writer
Santa Barbara, Ca.
[email protected]
805-687-4060
Vitamin C Saved 250,000 lives last year
After Linus Pauling wrote his book on vitamin C in 1970, mortality from heart disease decreased 30-40% in the USA. From around 741,000 deaths per year to less than 500,000 deaths by 1986 - U. S. Bureau of National Health Statistics 1986.
Yet, Vitamin C Attacks Continue. . .
BLOWING SMOKE
Sun Aug 12 10:17:52 CDT 2001
The continued stream of unfounded attacks generated massive worldwide news, usually before any published article is available for inspection, review or comment.
The latest (Aug 8th) attack blames vitamin C and vitamin E for "interfering" with statin anti-cholesterol drugs" and advises "cardiovascular patients not to take antioxidants." In our opinion, this is DEADLY advice, and we devote this PAGE to a discussion. As you blithely take your cholesterol lowering medication, keep this recent coincidental FDA action in mind: Statin Cholesterol Lowering Drug Recalled Due to Deaths
Who Are These Guys? Who Has the Power to Repeatedly Plant Fake Worldwide News Stories?
(The three most recent prior attacks were unfounded. They were either retracted or never published.) Remember, animals generally make large (multiple gram) amounts of vitamin C daily. They do not suffer any known DNA damage. These stories are based in simple economics, not rigorous science. Vitamin C leads to health and poses an economic threat to pharmaceutical-based medicine. - O. Fonorow
Who is behind these attacks
Even Linus Pauling Institute Attacks Vitamin C!
"The vast majority of all published studies on vitamin C supplementation show an overwhelmingly positive effect on health," said Phil Harvey, Ph.D.,
Yet again we are faced with a major media attack before any paper is published. These reports are usually based on some minor scientific finding, they are not fabrications, per se, but they are taken out of context and widely reported without having been published in a peer reviewed Journal. And according to Ralph Moss in his book Antioxidants Against Cancer, Page 45, retractions are not published:
"What I find particularly astonishing is that later in 1998, the authors of the original [widely reported] study published another report on vitamin C. This showed that people who received 500 milligrams of vitamin C per day had substantial benefit from the practice!
"These results illustrate... a role for vitamin C in the regulation of DNA repair enzymes," and demonstrate an "antioxidant effect," they wrote.
"Did you hear about these pro-vitamin C results? Probably not, because unlike the scare stories, these positive findings and comments passed without mention in the mainstread media.
- Ralph Moss
As the threat to the economic well being of Medicine and major Pharmaceutical companies (from vitamin C) increases, so do the groundless attacks designed to scare people from taking Vitamin C. (And according to published statistics - these attacks work. Vitamin C sales are off 19% year over year.)
If you doubt the impact of vitamin C on pharmaceutical profits, consider that after Linus Pauling wrote his book on vitamin C in 1970, mortality from heart disease decreased 30-40% in the USA. From around 741,000 deaths per year (National Center for Health Statistics, Pauling 86, p 164) to less than 500,000 deaths per year. Adam Smith's Invisible Hand works against us when it works for medicine without ethics. Fewer people with heart disease means enormous economic loss for the segments of our society that make money from heart disease.
Vitamin C Foundation
I've already figured out what is wrong with the researcher's work, and I'm a rank amateur at this.
The researcher dropped vitamin C into lipid hyperoxide to see if it would produce genotoxic materials.
Lipid hyperoxide is formed by free radical damage on lipids.
People who take vitamin C DO NOT FORM lipid hyperoxide because vitamin C is a free-radical scavenger.
In addition, lipid hyperoxide does a huge amount of bodily damage itself (such as heart disease plaques, I believe), and anything that combines with it would, under normal circumstances, be considered a good thing.
Thus what this researcher did was to take a reaction out of context using a scenario that cannot occur, and blamed vitamin C for forming potentially harmful compounds from a particularly nasty one. Typical bogus research.
Jon Campbell
Can you imagine how Science mag. would have responded if the said test-tube experiment had produced a group of anti-cancer, tumor-inhibiting compounds? Of course, they would have said "this needs further study and corroboration with animal or clinical tests before we can publish such a claim". Since the claim goes against Vitamin C, they put out the red carpet. It really is a transparent lie they have woven, fully understandable when you consider that 50% of the pages of Science mag. are composed of advertisements for the bio-tech and pharm industry. Reminds me when they were issuing all sorts of articles "proving" how save and efficient nuclear energy was.
James DeMeo, Ph.D.
Filed: 11/07/2001) Health.telegraph.co.uk
Dr Sarah Brewer on worries about too much vitamin C
DEAR DOCTOR - I take vitamin C and was alarmed by the recent sugg estions that high dose vitamin C might cause cancer. What is your opinion?
One of the authors of the recent paper in Science was so worried that his results would be misreported that he was quoted as saying: "Absolutely, for God's sake, don't say vitamin C causes cancer". Unfortunately, many reports did. The study used vitamin C to induce conversion of lipid hydroperoxides (which are formed in the body during the oxidation of unsaturated fats) into compounds that can damage DNA. This effect, demonstrated artificially in a test tube, cannot occur in living cells where a number of enzyme systems exist to remove the damaging substances formed. In addition, fat-soluble Vitamin E protects lipid cell membranes in living systems from oxidative reactions and, as vitamin C is essential for the regeneration of vitamin E, it actually plays an important role in preventing the formation of lipid hydroperoxides.
Other factors that make this a non-story include the fact that researchers used lipid hydroperoxide concentrations 10,000 times greater than those found in the body, and that the methods used to measure DNA could have caused the damage noted. There is ample evidence that vitamin C is beneficial in doses of up to 2g daily. A recent study of 19,196 adults aged 45 to 79 in Britain found that circulating levels of vitamin C were inversely related to death from all causes over the four-year study period. While diet should always come first, I will continue to take my supplements.
Knowledge of Health, Inc.
457 West Allen Avenue #117 San Dimas, California 91773
Telephone: 909.861.3454 Fax: 909.861.3442 Email: [email protected]
For Immediate Release 6.16.2001 Contact: Bill Sardi 909.861.3454
NEWS MEDIA AND TEST-TUBE
RESEARCHERS OVERLOOKED
FAVORABLE HUMAN STUDIES
ON VITAMIN C
SAN DIMAS, CA - Researchers at the University of Pennsylvania Center for Cancer Pharmacology and the news media overlooked five separate human studies that disproved high-dose vitamin C causes DNA damage and instead chose to make headlines out of a sole test-tube study that concluded that a 200-milligram dose of vitamin C could potentially cause cancer.
While millions of Americans who take vitamin C supplements were beginning to question whether high-dose vitamin C is safe, Ian A. Blair, the lead researcher in the study published in June 15 issue of Science magazine, was unavailable for comment and is travelling outside the country, leaving an air of uncertainty in the public's mind regarding vitamin C.
Usually test-tube studies precede animal or human studies, and results in the laboratory often do not coincide with those found in living systems. In this case, human studies had already been performed and have, as expected, not confirmed the notion that vitamin C is toxic to living cells or DNA.
Even though researchers are a bit puzzled as to why vitamin C supplements do not always reduce the risk for cancer, there are no studies that confirm that vitamin C supplement users are at greater risk for cancer.
Report overlooked contrary data
The report in Science was submitted in early February and approved for publication in May of 2001, and included other published references dated as late as the year 2000. Four of the five human studies that do not confirm that vitamin C causes DNA damage were published in 2000, and could have been cited by the authors of the report in Science, but were overlooked.
The five overlooked studies
For example, researchers at Johns Hopkins University could not find evidence of a "significant main effect or interaction effect on oxidative DNA damage in non-smoking adults" with 500 milligrams/day of vitamin C supplementation. [Cancer Epidemiology Biomarkers Prevention 2000 July;9:647-52]
Another study, conducted by researchers in Germany found that 1000 mg. of vitamin C consumed by smokers and non-smokers for 7 days did not produce DNA damage as measured by the number of micronuclei in blood lymphocytes. [Free Radical Research 2001 March;34:209-19]
In yet another study conducted by Immunosciences Laboratory in California, twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. This study concluded that "ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on natural killer cell activity, apoptosis, or cell cycle." [Cancer Detection Prevention 2000;24: 508-23]
In London researchers measured the effects of 260 milligrams/day of vitamin C and vitamin C + iron in humans and concluded that there was "no compelling evidence for a pro-oxidant effect of ascorbate supple- mentation, in the presence or absence of iron, on DNA base damage." [Biochemistry Biophysical Research Communications 2000 November 2;277:535-40]
In Ireland, researchers gave 1000 mg. of vitamin C to volunteers for 42 days and concluded that "supplementation with vitamin C decreased significantly hydrogen-peroxide-induced DNA damage in peripheral blood lymphocytes." [British Journal Nutrition 2000 August;84:195-202]
News media also remiss
The news media was also remiss in not checking whether there was any contrary data on this topic, and did not interview other scientific sources, such as the Linus Pauling Foundation, the Vitamin C Foundation, the National Nutritional Foods Association or the Council for Responsible Nutrition. Reuters Health and the Associated Press health reporters ran the story without checking on the validity of the report in Science. No explanation has been given for this oversight, even though science reporters for both organizations are well versed on medical topics. A cub reporter could have uncovered the five contrary human studies in a 30-minute search on Medline.
Similar erroneous report in 1998
Recently researchers have been exploring the dual nature of vitamin C. Is vitamin C a pro-oxidant or rusting agent, or is it an antioxidant, a cellular preservative? In 1998 Nature Magazine published a similar report to the University of Pennsylvania study. Researchers then claimed that high-dose vitamin C had "rusting" properties in living cells and that 500 milligrams of vitamin C was found to oxidize guanine, one of the four bases that make up DNA. But the researchers overlooked that high-dose vitamin C also increased the level of guanine, another of the nucleic acids in DNA. The researchers failed to point out their paradoxical results and the news media made headlines out of the story then, as they are doing now. No corrections were ever published. The mistaken impression left on the public then was that high-dose vitamin C is potentially dangerous.
It remains unclear whether the researchers at the University of Pennsylvania Center for Cancer Pharmacology will clear the air on their report, which received worldwide headlines. ####
June 14, 2001
TO: Will Dunham, health reporter for
REUTERS, Washington DC
[email protected]
FROM: Bill Sardi
Knowledge of Health, Inc.
Independent health journalist
Diamond Bar, California
[email protected]
I have questions regarding your recent report which alleges that vitamin C supplements beyond 200 milligrams per day may promote DNA damage that could cause cancer.
1. Were you aware this is not a new story, and that researchers can create DNA damage in test tubes, but not in living systems, with many essential nutrients or food factors found in the diet?
2. Why didn't your report carry interviews with those who have a differing opinion? Interviews could have been conducted with the Vitamin C Foundation, or the National Nutritional Foods Assn., or the Council for Responsible Nutrition? Did you seek to obtain balanced information?
3. Why did Reuters select this report from Science Magazine, and why did it run with the headlines "Vitamin C Found To Promote Cancer-Causing Agents?" rather than "Researchers study dual role of vitamin C in cancer???"
4. What do you think the impact of your report will be on the public at large, since many people take vitamin C supplements in doses that exceed what your article suggests as safe?
5. Are you aware of reports which show that consumption of vitamin C beyond 300 milligrams per day causes a major reduction in the risk of cataracts, and beyond 500 milligrams per day reduces the risk of hypertension? These dosages would generally required supplements rather than foods.
6. Are you aware that, in July of 2000, researchers found that supplementation of diet with vitamin C (500 mg/day) had no significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in nonsmoking adults. [Cancer Epidemiol Biomarkers Prev 2000 Jul;9(7):647-52] In other words, high-dose vitamin C did not produce any measurable DNA damage.
The very issue of whether vitamin C promotes DNA damage was undertaken in 1998 by researchers at the International Antioxidant Research Centre, Department of Pharmacology, King's College, London, United Kingdom. [Biochem Biophys Res Commun 1998 May 8;246(1):293-8] They reported on the effects of co-supplementing healthy volunteers with iron (14 mg/day ferrous sulphate) and vitamin C (either 60 mg/day or 260 mg/day as ascorbic acid) on levels of oxidative DNA damage in white blood cells. The subjects were divided into two groups: one group of 20 volunteers with a higher mean initial level of plasma vitamin C (71.9 +/- 14.0 mumol/l) and a second group of 18 volunteers with a lower mean level (50.4 +/- 25.8 mumol/l). In the first group there was a significant rise in several oxidative DNA base damage products and in total oxidative DNA damage in DNA extracted from white blood cells, but not in 8-hydroxyguanine, after 6 weeks of supplementation. However, after 12 weeks levels returned approximately to normal. In the group with the lower initial level of plasma ascorbate, presupplemental levels of oxidative DNA damage were higher and decreased on supplementation with iron and ascorbate.
A recent study, reported in the January issue of Cancer Epidemiology Biomarkers, indicates, among 711,891 men and women in the United States, followed from 1982 thru 1996, regular use of vitamin C supplements, even long-term use, was not associated with colorectal cancer mortality. The combined-sex rate ratios were 0.89 for 10 or more years of vitamin C use, a slight reduction in the risk for cancer. In subgroup analyses, use of vitamin C supplements for 10 or more years was associated with decreased risk of colorectal cancer mortality before age 65 years, 52% relative reduced risk, and 60% reduced risk reduced risk for rectal cancer mortality. [Cancer Epidemiol Biomarkers Prev 2001 Jan;10(1):17-23]
In India researchers used high-dose vitamin C in animals exposed to cigarette smoke and found that vitamin C supplementation increased resistance to lipid peroxidation and "this study seems to suggest that an intake of a mega dose of vitamin C can protect the liver from oxidant damage caused by cigarette smoke." [J Appl Toxicol 1997 Sep-Oct;17(5):289-95]
In 1999 researchers at the Fred Hutchinson Cancer Research Center in Seattle reported that supplement use in 697 incident prostate cancer cases (ages 40-64) identified from the Puget Sound Surveillance, Epidemiology and End Results program registry. Adjusted odds ratios vitamin C, 0.77 (range 0.57 - 1.04), about a 23% relative reduced risk. The researchers said: "Overall, these results suggest that multivitamin use is not associated with prostate cancer risk." [Cancer Epidemiol Biomarkers Prev 1999 Oct;8(10):887-92]
Any cub reporter could have found these reports in just 30 minutes on Medline. Why weren't reports like these incorporated into your report? In light of these scientific studies, would you call your report fair and balanced?
Shame on the Linus Pauling Institute
The latest attack quotes so-called authorities at the Linus Pauling Institute. If these quotes are accurate, the institute now uses Pauling's name, but lacks his spirit. Dr. Frei has not read Pauling's HOW TO LIVE LONGER AND FEEL BETTER, else he would not make such inaccurate statements using Pauling's name. We would ask any contributor to check with the Pauling Institute, re-read HOW TO LIVE LONGER AND FEEL BETTER, and reconsider giving the institute any more money until Dr. Frei leaves his post.
REUTERS NEWS REPORT Thursday June 14 3:11 PM ET
Vitamin C Found to Promote Cancer-Causing Agents
By Will Dunham
WASHINGTON (Reuters) - Vitamin C, an essential nutrient found in fruits and
vegetables and taken in large doses by many people as a dietary supplement,
is a double-edged sword, providing benefits but also inducing the production
of compounds associated with cancer, researchers said on Thursday.
Researchers at the University of Pennsylvania added vitamin C, also known as
ascorbic acid, to solutions of a degraded version of an important fatty acid
found in blood, and found that it triggered the production of DNA-damaging
agents known to cause mutations associated with a variety of cancers.Lead
researcher Ian Blair of the university's Center for Cancer Pharmacology
cautioned that the study was conducted in a test tube and not with living
human cells or in actual people.
``Absolutely for God's sake don't say vitamin C causes cancer,'' Blair said
in a telephone interview.``
The key finding is that vitamin C can do good things and bad things. And
we've figured out what the bad ones are. In terms of the impact, I think it
just redirects people's attention to the fact that you can't replace a good
diet with magic bullets such as vitamin C.''The value of vitamin C has been
the subject of a long and heated debate in the scientific community. One of
the leading scientists of the 20th century, Linus Pauling, who died at age 93
in 1994, championed it as a tool for fighting cancer.But skeptics argued that
numerous studies have found that vitamin C produced no benefit in combating
cancer, and that taking supplements actually could have negative
consequences. The new study appears to add weight to those concerns.
CAUTION URGED ON DIETARY SUPPLEMENTS
``Far more caution should be taken in the use of dietary supplements -- and
an insistence on real proof that there's a benefit before undertaking any of
them,'' said Dr. Arthur Grollman, director of the Laboratory for Chemical
Biology at the State University of New York at Stony Brook.``The real,
serious implication is that it (vitamin C) could contribute to DNA damage
that could cause cancer,'' added Grollman, an expert in cancer causes who was
not involved in the study. ``It just adds more evidence that there could be a
significant risk to ascorbic acid.''Blair said the study, which appears in
the journal Science, may explain why vitamin C has shown little effectiveness
at preventing cancer in clinical trials.
Vitamin C is a water-soluble vitamin that is important for bone and
connective tissue growth, wound repair and the function of blood vessels. It
is abundant in citrus fruits, green peppers, tomatoes, cabbage and potatoes.
The recommended U.S. adult dietary allowance for vitamin C is 60 milligrams
daily. Most supplements contain many times that amount.Dr. Garret FitzGerald,
director of the University of Pennsylvania's Center for Experimental
Therapeutics, pointed to evidence of a benefit from an overall healthy diet
rather than taking supplements on any particular nutrient.``We have very
clear evidence that eating a diet rich in vegetables and fruits is a healthy
thing in terms of it being associated with a reduced incidence of cancer and,
indeed, heart disease, for that matter,'' FitzGerald said.
``On the one hand, I would say to people there's no evidence to stop taking
vitamin C on the basis of these observations at this point in time. On the
other hand, I'd say consider very carefully what the evidence is for taking
vitamin C, which is nonexistent. The better part of valor is: save your
money.''
VITAMIN C IS AN ANTIOXIDANT
Vitamin C acts as an antioxidant protecting against damage by ``free radicals'' -- highly reactive ions produced by the breakdown of oxygen in cells. In addition to damaging DNA directly, free radicals also can act indirectly.They begin by converting linoleic acid, the major polyunsaturated fatty acid in human blood plasma and the key polyunsaturated fatty acid in certain cooking oils, into another compound called a lipid hydroperoxide.When certain metal ions are present as catalysts, the compound degrades into DNA-damaging agents called genotoxins, which cause mutations that have been found in human tumors. Blair said he had a hunch that vitamin C might be capable of changing lipid hydroperoxides into genotoxins. He added vitamin C to test tube solutions of lipid hydroperoxides, using concentrations comparable to those found in the human body if a person were taking 200 milligrams a day.The study found that vitamin C was more than twice as efficient as transition metal ions at inducing the formation of genotoxins, including a particularly potent variety.
Read About the Role of Vitamin C in Heart Disease
Knowledge of Health, Inc.
457 West Allen #117 San Dimas, California 91773
Phone: 909.861.3454 Fax: 909.861.3442 E-mail: [email protected]
For Immediate Release Contact: Bill Sardi 909.861.3454
Who is Behind The Negative News Reports On Vitamin C?
The news media features a report published in Science magazine that high-dose vitamin C in a test-tube causes DNA damage that could lead to cancer. It's not news, since test-tube studies do not correlate with tests conducted in living systems and the dual role of vitamin C as both a pro-oxidant (rusting agent) and anti-oxidant (cell preservative) has been published in scientific journals for some time now. But it's a heralded news story that Reuters Health and the Associated Press embellish with sensational headlines. Instead of saying "Dual nature of vitamin C in cancer explored," the headlines read "Vitamin C Found to Promote Cancer- Causing Agents." It's yellow journalist at its worst, since a quick search on Medline reveals that high-dose vitamin C did not reveal any toxic by-products in human studies. The toxic effect is only observed in test tubes.
The lead university researcher, Ian Blair of the University of Pennsylvania Center for Cancer Pharmacology, is conveniently outside the country, so he can't easily respond to questions. Ian Blair, covers his story by saying "Absolutely, for God's sake, don't say vitamin C causes cancer." But the headlines read otherwise.
The University of Pennsylvania is the originator of Oncolink, a prestigious online resource of cancer information. But who sponsors Oncolink? Hidden behind the whole affair are Oncolink's sponsors --- the pharmaceutical companies. AstraZeneca, Amgen, Ortho Biotech, Pharmacia, Pfizer and Janssen Pharmaceuticals. Are the drug companies using a major university as their shill to spread misinformation about vitamins?
It is becoming more obvious that misinformation about vitamins, minerals and herbal products is being planted in the news media and published in medical journals in a calculated fashion. The reason is that more and more Americans are taking health care into their own hands and relying less and less on doctors and drugs to cure their ills. The big secret is that the biological action of virtually every prescription drug can be duplicated with nutritional supplements at far less cost and with fewer side effects. The only way to counter the growing demand for natural remedies is to confuse the public with misinformation.
And the misinformation campaign is working. The natural products industry reports their growth has leveled off. Vitamin C sales were off by 19.2 percent last year according to a report in Natural Foods Merchandiser. In the past months dubious negative reports have been published on garlic, St. John's wort, and products containing ephedra. A characteristic of all these reports is their emphatic conclusion that all previous research which confirmed the validity of these natural remedies is to be discarded because the latest scientific report reached a contrary conclusion.
Last year the news media made a front- page headline story out of a presentation on vitamin C at the American Heart Association meeting. The study wasn't even published and hadn't undergone peer review, but the news agencies were quick to release a factitious story that high-dose vitamin C could clog arteries in the neck (the carotids). Vitamin C does not clog arteries, but it does strengthen and thicken the walls of arteries via its ability to promote collagen formation.
How do these non-news stories get front-page coverage? It's simple. Public relations agencies have bragged at seminars how they can take a presentation at a medical meeting and get it aired on television and published in newspapers. These publicity agencies do the dirty work of planting misinformation in the news media. It's propaganda, not news.
The natural products industry is mounting its own public information campaign, to counter negative news stories, and has hired their own agency, Hill & Knowlton of Washington, D.C., to air its side of the story.
There are simply no standards of journalism being upheld here. Bad science gets front-page coverage regardless of whether it is true or not. Journalists aren't checking on the validity of medical reports, and they aren't interviewing opposing views. In the case of the recent vitamin C report, reporters did not interview the National Nutritional Foods Association, the Council for Responsible Nutrition, the Vitamin C Foundation, nor the American Healthcare Products Association.
But how long can the public be fooled? Why are the pharmaceutical companies so afraid of a simple vitamin? It's because high doses of vitamin C virtually eradicate the risk of developing cataracts, eliminate the need for blood pressure medication, reduce the need for anti-allergy drugs, reduce the risk of gall stones, and produce many other health benefits. The drug companies can't invent and patent a molecule as efficacious as vitamin C. ####
Questions for Study Authors and Media
TO: Owen Fonorow
VITAMIN C FOUNDATION
FROM: Bill Sardi
I just E-mailed this inquiry to Ian A. Blair, the lead researcher of the
now infamous vitamin C report in Science Magazine.
June 15, 2001
TO: Ian A. Blair
Center for Cancer Pharmacology
University of Pennsylvania
[email protected]
FROM: Bill Sardi
Health reporters, Nutrition Science News
[email protected]
Phone: 909.861.3454
Diamond Bar, California USA
Unfortunately your paper in SCIENCE regarding ascorbic acid and DNA damage was published while you were out of the country and unavailable for quick comment. Of course, it is disappointing that the news media made such headlines out of research that does not appear to be new. The issue of whether vitamin C is a pro-oxidant or anti-oxidant has been debated for some time now. The fact that your paper concluded from a test-tube study that vitamin C concentrations equivalent to a 200 mg. dosage in humans could be genotoxic is not confirmed by epidemiological or human studies which your paper did not cite.
The submission date on your paper was February 2001, and your paper cited other references as late year 2000. The following reports, which includes reports up to the year 2000, encompassing a review of human studies with vitamin C and DNA damage, do not confirm your findings, and should have been included in your paper, am I correct?
I was wondering why your paper did not cite these references and why you did not inform the news media that your findings were not confirmed by human nor epidemiological studies? Your comments to the news media left the door open that it is possible for vitamin C to promote cancer. The references below are for your review, with the total abstracts following. Don't you think you should clear this matter up by clarifying the conclusion from your paper in light of other contrary research studies conducted outside of test tubes?
For example, researchers at Johns Hopkins University could not find evidence of a "significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in non-smoking adults" with 500 milligrams/day of vitamin C supplementation. [Cancer Epidemiol Biomarkers Prev 2000 Jul;9(7):647-52]
Another study, conducted by researchers in Germany found that 1000 mg. of vitamin C consumed by smokers and non-smokers for 7 days did not produce DNA damage as measured by the number of micronuclei in blood lymphocytes. [Free Radic Res 2001 Mar;34(3):209-19]
In yet another study conducted by Immunosciences Laboratory, twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. This study concluded that "ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle." [Cancer Detect Prev 2000;24(6):508-23]
In London researchers measured the effects of 260 milligrams/day of vitamin C and vitamin C + iron in humans and concluded that there was "no compelling evidence for a pro-oxidant effect of ascorbate supplementation, in the presence or absence of iron, on DNA base damage measured by GC-MS." [Biochem Biophys Res Commun 2000 Nov 2;277(3):535-40]
In Ireland, researchers gave 1000 mg. of vitamin C to volunteers for 42 days and concluded that "supplementation with vitamin C decreased significantly H2O2-induced DNA damage in peripheral blood lymphocytes." [Br J Nutr 2000 Aug;84(2):195-202]
I await your comment.
Cancer Epidemiol Biomarkers Prev 2000 Jul;9(7):647-52
The effects of vitamin C and vitamin E on oxidative DNA damage: results from a randomized controlled trial.
Huang HY, Helzlsouer KJ, Appel LJ.
Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205-2223, USA.
Oxidative DNA damage may be important in mutagenic, carcinogenic, and aging processes. Although it is plausible that antioxidant vitamins may reduce oxidative DNA damage, evidence from human studies has been sparse and inconsistent. We determined the short-term effects of vitamin C (500 mg/day) and vitamin E (400 IU d-alpha-tocopheryl acetate/day) supplements on oxidative DNA damage in a double-masked, placebo-controlled, 2x2 factorial trial in 184 nonsmoking adults. Mean duration of supplementation was 2 months. Oxidative DNA damage was measured by 24-h urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG). At baseline, urinary 8-OHdG (mean +/- SE; ng/mg creatinine) was associated with race (15.6 +/- 0.8 in African Americans versus 20.3 +/- 1.2 in Caucasians, P = 0.001), prior antioxidant supplement use (18.6 +/- 0.8 in users versus 13.8 +/- 1.5 in non-users, P = 0.007), and regular exercise (19.2 +/- 1.1 in exercisers versus 16.6 +/- 0.9 in non-exercisers, P = 0.04). Fruit and vegetable intake and serum ascorbic acid were inversely associated with urinary 8-OHdG (P-trend = 0.02 and 0.016, respectively). The benefits of fruit and vegetable intake became evident with the consumption being at least three servings/day. At the end of supplementation, change from baseline in urinary 8-OHdG (mean +/- SE; ng/mg creatinine) was -0.6 +/- 1.4 (P = 0.61), 0.6 +/- 1.1 (P = 0.59), 0.5 +/- 1.0 (P = 0.61), and 1.6 +/- 1.4 (P = 0.27) in the placebo, vitamin C alone, vitamin E alone, and combined vitamins C and E groups, respectively. In overall and subgroup analyses, there was no significant main effect or interaction effect of the supplements on urinary 8-OHdG. In conclusion, supplementation of diet with vitamin C (500 mg/day) and vitamin E (400 IU d-alpha-tocopheryl acetate/day) had no significant main effect or interaction effect on oxidative DNA damage as measured by urinary 8-OHdG in nonsmoking adults. However, several aspects of a healthy lifestyle were associated with lower oxidative DNA damage.
Free Radic Res 2001 Mar;34(3):209-19
Protective Effects of Vitamins C and E on the Number of Micronuclei in Lymphocytes in Smokers and their Role in Ascorbate Free Radical Formation in Plasma.
Schneider M, Diemer K, Engelhart K, Zankl H, Trommer WE, Biesalski HK.
Fachbereich Biologie / Abteilung Humanbiologie der Universitaet Kaiserslautern, Germany.
Cigarette smoke is widely believed to increase free radical concentrations causing subsequent oxidative processes that lead to DNA damage and hence, to several diseases including lung cancer and atherosclerosis. Vitamin C is a reducing agent that can terminate free-radical-driven oxidation by being converted to a resonance-stabilized free radical. To investigate whether short-term supplementation with the antioxidants vitamin C and E decreases free-radical-driven oxidation and thus decreases DNA damage in smokers, we determined the frequency of micronuclei in lymphocytes in 24 subjects and monitored the electron paramagnetic resonance signal of ascorbate free radical formation in plasma. Further parameters comprised sister-chromatid exchanges and thiobarbituric acid-reactive substances. Twelve smokers and twelve non-smokers took 1000 mg ascorbic acid daily for 7 days and then 1000 mg ascorbic acid and 335.5 mg RRR-alpha-tocopherol daily for the next 7 days. Baseline concentrations of both vitamins C and E were lower and baseline numbers of micronuclei were higher (p < 0.0001) in smokers than in non-smokers. After 7 days of vitamins C and E, DNA damage as monitored by the number of micronulei was decreased in both, smokers and non-smokers, but it was more decreased in smokers as indicated by fewer micronuclei in peripheral lymphocytes (p < 0.05). Concomitantly, the plasma concentrations of vitamin C (p < 0.001) as well as the ascorbate free radical (p < 0.05) were increased. The corresponding values in non-smokers, however, did not change. Our findings show that increased ascorbate free radical formation in plasma after short-term supplementation with vitamins C and E can decrease the number of micronuclei in blood lymphocytes and thus DNA damage in smokers.
Cancer Detect Prev 2000;24(6):508-23
New evidence for antioxidant properties of vitamin C
Vojdani A, Bazargan M, Vojdani E, Wright J.
Immunosciences Lab, Inc, Beverly Hills, CA 90211, USA.
This study was designed to examine the effect of 500 to 5,000 mg of ascorbic acid on DNA adducts, natural killer (NK) cell activity, programmed cell death, and cell cycle analysis of human peripheral blood leukocytes. According to our hypothesis, if ascorbic acid is a pro-oxidant, doses between 500 and 5,000 mg should enhance DNA adduct formation, decrease immune function, change the cell cycle progression, and increase the rate of apoptosis. Twenty healthy volunteers were divided into four groups and given either placebo or daily doses of 500, 1,000 or 5,000 mg of ascorbic acid for a period of 2 weeks. On days 0, 1, 7, 15, and 21, blood was drawn from them, and the leukocytes were separated and examined for intracellular levels of ascorbic acid, the level of 8-hydroxyguanosine, NK cell activity, cell cycle progression, and apoptosis. Depending on the subjects, between a 0% and a 40% increase in cellular absorption of ascorbic acid was observed when daily doses of 500 mg were used. At doses greater than 500 mg, this cellular absorption was not increased further, and all doses produced equivalent increases in ascorbic acid on days 1 to 15. This increase in cellular concentration of ascorbic acid resulted in no statistically meaningful changes in the level of 8-hydroxyguanosine, increased NK cytotoxic activity, a reduced percentage of cells undergoing apoptosis, and switched cell cycle phases from S and G2/M to G0/G1. After a period of 1 week, with no placebo or vitamin washout, ascorbic acid levels along with functional assays returned to the baseline and became equivalent to placebos. In comparison with baseline values, no change (not more than daily assays variation) was seen in ascorbate concentrations or other assays during oral placebo treatment. We concluded that ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle.
Biochem Biophys Res Commun 2000 Nov 2;277(3):535-40
Potential problems of ascorbate and iron supplementation: pro-oxidant effect in vivo?
Proteggente AR, Rehman A, Halliwell B, Rice-Evans CA.
Wolfson Centre for Age-Related Diseases, GKT School of Biomedical Sciences, King's College London, St. Thomas' Street, London, SE1 9RT, United Kingdom.
The comparison was undertaken between the effects of ascorbate versus ascorbate plus iron supplementation on DNA damage. Twenty healthy subjects with initial levels of plasma ascorbate of 67.2 +/- 23.3 micromol/l were randomly assigned to and cycled through one of three supplementation regimes: placebo, 260 mg/d ascorbate, 260 mg/d ascorbate plus 14 mg/d iron for 6 weeks separated by 8-week washout periods. Supplementation did not cause a rise in total oxidative DNA damage measured by GC-MS. However, a significant decrease occurred in levels of 8-oxo-7,8-dihydroguanine by ascorbate supplementation and 5-hydroxymethyl uracil by both ascorbate and ascorbate plus iron supplementation, relative to the pre-supplemental levels but not to the placebo group. In addition, levels of 5-hydroxymethyl hydantoin and 5-hydroxy cytosine increased significantly, only relative to pre-supplementation, by ascorbate plus iron treatment. No compelling evidence for a pro-oxidant effect of ascorbate supplementation, in the presence or absence of iron, on DNA base damage was observed. Copyright 2000 Academic Press.
Br J Nutr 2000 Aug;84(2):195-202
The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes.
Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA.
Cancer and Ageing Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland.
There is a wealth of epidemiological information on antioxidants and their possible prevention of disease progression but very little of the research on antioxidants has involved intervention studies. In this study, the potential protective effect of vitamin C or E supplementation in vivo against endogenous and H2O2-induced DNA damage levels in lymphocytes was assessed. The supplementation involved fourteen healthy male and female non-smokers mean age 25-53 (SD 1.82) years, who were asked to supplement an otherwise unchanged diet with 1000 mg vitamin C daily for 42 d or 800 mg vitamin E daily for 42 d. DNA damage in H2O2-treated peripheral blood lymphocytes (PBL) and untreated PBL before and after supplementation, and during a 6-week washout period was assessed using an ELISA. At each sampling time-point, the red cell concentrate activities of superoxide dismutase, catalase and glutathione peroxidase were also determined. Supplementation with vitamin C or vitamin E decreased significantly H2O2-induced DNA damage in PBL, but had no effect on endogenous levels of DNA damage. The activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were suppressed during the supplementation period. These supplementation regimens may be used to limit the possible adverse effects of reactive oxygen species (including those produced during the course of an immune response) on lymphocytes in vivo, and so help to maintain their functional capacity.
NNFA leaves the door open to doubt, which would be enough for many consumers to reduce their dosage of vitamin C supplements. See the sentence below which says: "While it is possible that these lipids may be converted to genotoxins, which in turn may damage DNA, it is far from conclusive that this is a cancer-causing mechanism." --- Phil Harvey, NNFA director of science and quality assurance
Vitamin C Study Premature and Inconclusive
June 15, 2001
Numerous studies over the past 30 years have demonstrated a preponderance of scientific evidence about vitamin C's positive effects, including its cancer-preventing properties. A report published yesterday in the journal Science suggests vitamin C may have carcinogenic properties - a claim that has been presented in media reports as fact. This is a dangerous and questionable leap based on a single survey compared with substantial amounts of scientific literature that indicates otherwise.
"The vast majority of all published studies on vitamin C supplementation show an overwhelmingly positive effect on health," said Phil Harvey, Ph.D., NNFA's director of science and quality assurance. "Yet this study, which was performed in a test tube - not on humans, is being represented as evidence that vitamin C is potentially harmful. Even the study's lead researcher is quoted as saying, 'Absolutely, for God's sake, don't say vitamin C causes cancer.' Yet that is exactly what is occurring."
"We are extremely concerned that consumers may hear only a portion of these reports and change their vitamin C supplementation, a change that may put their health at risk because of all the demonstrable benefits of this vitamin," Harvey said.
The study, conducted at the University of Pennsylvania, involved adding vitamin C, also known as ascorbic acid, to test tubes containing solutions of fatty acids found in the blood. According to researchers, adding vitamin C triggered mutation-causing agents identified with the development of cancer.
According to the NNFA, mutations continually occur in cells and to conclude that high doses of vitamin C cause this to happen is pure speculation and reckless.
The researchers tested lipid peroxidation (lipid hydroperoxide) from dietary fat. While it is possible that these lipids may be converted to genotoxins, which in turn may damage DNA, it is far from conclusive that this is a cancer-causing mechanism. Humans have complex biochemical mechanisms to deal with lipid peroxidations and other nutrients. For instance, vitamin E protects and augments the effect of vitamin C. Because other antioxidants were not present in the laboratory tests, the synergistic effect that would normally occur in the human body was prevented.
Many previous studies and recommendations by government agencies contradict the findings of this study, including:
Research by the National Cancer Institute that supports vitamin C's beneficial effects on reducing the risk of cancer. A health claim authorized by the Food and Drug Administration that fruits and vegetables high in vitamin C can reduce the risks of some cancers. The recent recommendation by the Institute of Medicine that daily vitamin intake be increased because of its disease-prevention properties.
Evidence that vitamin C enhances the effects of certain chemotherapy drugs, reduces toxicity of chemotherapeutic agents, and may actually prevent cancer NNFA recommends that consumers eat a diet rich in fruits and vegetables and other natural sources of vitamin C and other antioxidants. In addition, NNFA recommends supplementation with vitamin C to further realize the benefits of vitamin C contained in food.
"People should not stop taking vitamin C based on the premature conclusions from a single, contradictory study," said Harvey. "The real danger here is not from vitamin C, but from sensationalized reports that will cause consumers to stop using a supplement that is clearly beneficial to their health." NNFA also recommends that members write letters to the editor of their local newspapers when stories about the study are printed. Members are free to use the text of this alert or access the press release online at www.nnfa.org/news/press_releases/index.htm.
For an in depth look at this study and research on vitamin C, please look in the April 2000 issue of NNFA Today.
Date: Mon 25 Jun 2001
Re: "Effects of Vite C are still causing a healthy debate" L.A.Times article Mon 25 June 2001
Somehow the title of your article was lost on me... did I miss something? Where exactly was the debate. You failed to interview or quote even one of the many proponents of ascorbate who advocate ascorbates in generous amounts. Where are the Ph.d.'s or M.D.'s who have been at the fore front of Vitamin C (ascorbate is the correct term) research and orthomolecular medicine's mega-dose ascorbate treatments.
Also mysteriously absent from the article was the reason humans require "C" in the first place. Where was the overview of the topic. Most folks do not realize that a genetic fault is responsible for the ascorbate deficiency in humans. Almost every mammal makes copious amounts of ascorbate in their livers, and understress and toxic environmental conditions they produce far more yet. We are talking about 5-20 grams par day.
The L.A. Times article was simply wrong about far too many things and was lacking in a baseline of knowledge as to how and why ascorbates effect human physiology. The fact that this article by Benedict Carey was missing the word "ascorbate" tells us a lot about the writer and pathetically little about the real story of ascorbate and human physiology. May I suggestto Benedict Carey (before further embarrassment) that the following sites be reviewed and understood before more articles aboutascorbates are published.
www.vitamincfoundation.org
www.cforyourself.com
www.paulingtherapy.com
Read on.
Sascha Sarnoff, Health Advocate/Writer
Santa Barbara, Ca.
[email protected]
805-687-4060
Vitamin C Saved 250,000 lives last year
CANCER - Coenzyme Q10
FROM NATIONAL CANCER INSTITUTE
http://www.cancer.gov/cancer_information/doc.aspx?viewid=0E5B4097-610C-4A49-844F-D935F1D7BB07#6
Coenzyme Q10 (PDQ®)
Updated: 05/01/2002
Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Overall Level Of Evidence for Coenzyme Q10
References
For More Information
Overview
This complementary and alternative medicine (CAM) information summary provides an overview of the use of coenzyme Q10 in cancer therapy. The summary includes a history of coenzyme Q10 research, a review of laboratory studies, and data from investigations involving human subjects. Although several naturally occurring forms of coenzyme Q have been identified, Q10 is the predominant form found in humans and most mammals, and it is the form most studied for therapeutic potential. Thus, it will be the only form of coenzyme Q discussed in this summary. Many of the medical and scientific terms used in the summary are hypertext linked (at first use only) to the Cancer.gov Dictionary, which is oriented toward non-experts. When a linked term is clicked, a definition will appear in a separate window. All linked terms and their corresponding definitions will appear as a glossary in the printable version of the summary.
This summary contains the following key information:
· Coenzyme Q10 is made naturally by the human body.
· Coenzyme Q10 helps cells to produce energy, and it acts as an antioxidant.
· Coenzyme Q10 has shown an ability to stimulate the immune system and to protect the heart from damage caused by certain chemotherapy drugs.
· Low blood levels of coenzyme Q10 have been detected in patients with some types of cancer.
· No report of a randomized clinical trial of coenzyme Q10 as a treatment for cancer has been published in a peer-reviewed, scientific journal.
· Coenzyme Q10 is marketed in the United States as a dietary supplement.
General Information
Coenzyme Q10 (also known as Co Q10, Q10, vitamin Q10, ubiquinone, or ubidecarenone) is a benzoquinone compound synthesized naturally by the human body. The "Q" and the "10" in the name refer to the quinone chemical group and the 10 isoprenyl chemical subunits, respectively, that are part of this compound's structure. The term "coenzyme" denotes it as an organic (contains carbon atoms), nonprotein molecule necessary for the proper functioning of its protein partner (an enzyme or an enzyme complex). Coenzyme Q10 is used by cells of the body in a process known variously as aerobic respiration, aerobic metabolism, oxidative metabolism, or cell respiration. Through this process, energy for cell growth and maintenance is created inside cells in compartments called mitochondria.[reviewed in 1-4] Coenzyme Q10 is also used by the body as an endogenous antioxidant.[reviewed in 1,2,4,5,7-9] An antioxidant is a substance that protects cells from free radicals, which are highly reactive chemicals, often containing oxygen atoms, capable of damaging important cellular components such as DNA and lipids. In addition, the plasma level of coenzyme Q10 has been used, in studies, as a measure of oxidative stress (a situation in which normal antioxidant levels are reduced).[10,11]
Coenzyme Q10 is present in most tissues, but the highest concentrations are found in the heart, the liver, the kidneys, and the pancreas.[6] The lowest concentration is found in the lungs.[6] Tissue levels of this compound decrease as people age, due to increased requirements, decreased production,[6] or insufficient intake of the chemical precursors needed for synthesis.[reviewed in 12] In humans, normal blood levels of coenzyme Q10 have been defined variably, with reported values ranging from 0.30 to 3.84 micrograms per milliliter.[13,14,reviewed in 2,4]
Given the importance of coenzyme Q10 to optimal cellular energy production, use of this compound as a treatment for diseases other than cancer has been explored. Most of these investigations have focused on coenzyme Q10 as a treatment for cardiovascular disease.[15,reviewed in 2,4] In patients with cancer, coenzyme Q10 has been shown to protect the heart from anthracycline-induced cardiotoxicity (anthracyclines are a family of chemotherapy drugs, including doxorubicin, that have the potential to damage the heart)[3,16-18] and to stimulate the immune system.[19, reviewed in 20] Stimulation of the immune system by this compound has also been observed in animal studies and in humans without cancer.[21-27] In part because of its immunostimulatory potential, coenzyme Q10 has been used as an adjuvant therapy in patients with various types of cancer.[17,28,29,30, reviewed in 20,31-33]
While coenzyme Q10 may show indirect anticancer activity through its effect(s) on the immune system, there is evidence to suggest that analogs of this compound can suppress cancer growth directly. Analogs of coenzyme Q10 have been shown to inhibit the proliferation of cancer cells in vitro and the growth of cancer cells transplanted into rats and mice.[12,34] In view of these findings, it has been proposed that analogs of coenzyme Q10 may function as antimetabolites to disrupt normal biochemical reactions that are required for cell growth and/or survival and, thus, that they may be useful for short periods of time as chemotherapeutic agents.[12,34]
Several companies distribute coenzyme Q10 as a dietary supplement. In the United States, dietary supplements are regulated as foods not drugs. Therefore, premarket evaluation and approval by the Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, there may be considerable variation from lot to lot.
To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. The IND application process is highly confidential, and IND information can be disclosed only by the applicants. To date, no investigators have announced that they have applied for an IND to study coenzyme Q10 as a treatment for cancer.
In animal studies, coenzyme Q10 has been administered by injection (intravenous, intraperitoneal, intramuscular, or subcutaneous). In humans, it is usually taken orally as a pill (tablet or capsule), but intravenous infusions have been given.[4] Coenzyme Q10 is absorbed best with fat; therefore, lipid preparations are better absorbed than the purified compound.[reviewed in 2,4] In human studies, supplementation doses and administration schedules have varied, but usually have been in the range of 90 to 390 milligrams per day.
History
Coenzyme Q10 was first isolated in 1957,[reviewed in 2] and its chemical structure (benzoquinone compound) was determined in 1958.[reviewed in 13] Interest in coenzyme Q10 as a therapeutic agent in cancer began in 1961, when a deficiency was noted in the blood of both Swedish and American cancer patients, especially in the blood of patients with breast cancer.[13, reviewed in 30,32] A subsequent study showed a statistically significant relationship between the level of plasma coenzyme Q10 deficiency and breast cancer prognosis.[14] Low blood levels of this compound have been reported in patients with malignancies other than breast cancer, including myeloma, lymphoma, and cancers of the lung, prostate, pancreas, colon, kidney, and head and neck.[12,13 reviewed in 31] Furthermore, decreased levels of coenzyme Q10 have been detected in malignant human tissue,[35-39] but increased levels have been reported as well.[35]
A large amount of laboratory and animal data on coenzyme Q10 has accumulated since 1962.[reviewed in 13] Research into cellular energy producing mechanisms that involve this compound was awarded the Nobel Prize in chemistry in 1978. Some of the accumulated data show that coenzyme Q10 stimulates animal immune systems, leading to higher antibody levels,[21] greater numbers and/or activities of macrophages and T cells (T lymphocytes),[21,23] and increased resistance to infection.[24-26] Coenzyme Q10 has also been reported to increase IgG (immunoglobulin G) antibody levels and to increase the CD4 to CD8 T-cell ratio in humans.[19,22,27] CD4 and CD8 are proteins found on the surface of T cells, with CD4 and CD8 identifying "helper" T cells and "cytotoxic" T cells, respectively; decreased CD4 to CD8 T-cell ratios have been reported for cancer patients.[40,41] Research subsequently delineated the antioxidant properties of coenzyme Q10.[10,11, reviewed in1,4,6]
Proposed mechanisms of action for coenzyme Q10 that are relevant to cancer include its essential function in cellular energy production and its stimulation of the immune system (the two of which may be related), as well as its role as an antioxidant. Coenzyme Q10 is essential to aerobic energy production,[reviewed in 1-3] and it has been suggested that increased cellular energy may lead to increased antibody synthesis in B cells (B lymphocytes).[12,19] As noted previously (General Information section), coenzyme Q10 can also behave as an antioxidant.[reviewed in 1,2,4-9] In this capacity, coenzyme Q10 is thought to stabilize cell membranes (lipid-containing structures essential to maintaining cell integrity) and to prevent free radical damage to other important cellular components.[reviewed in 1,2,6,9] Free radical damage to DNA (and possibly to other cellular molecules) may be a factor in cancer development.[reviewed in 7,10,38,42-45]
Laboratory/Animal/Preclinical Studies
Laboratory work on coenzyme Q10 has focused primarily on its structure and its function in cell respiration. Studies in animals have demonstrated that coenzyme Q10 is capable of stimulating the immune system, with treated animals showing increased resistance to protozoal infections [25,26] and to viral and chemically induced neoplasia.[24-26, reviewed in 13] Early studies of coenzyme Q10 showed increased hematopoiesis (the formation of new blood cells) in monkeys,[reviewed in 13,17] rabbits,[46] and poultry.[reviewed in 17] Coenzyme Q10 demonstrated a protective effect on the heart muscle of mice, rats, and rabbits given the anthracycline anticancer drug doxorubicin.[47-52] Although another study confirmed this protective effect with intraperitoneal administration of doxorubicin in mice, it failed to demonstrate a protective effect when the anthracycline was given intravenously, which is the route of administration in humans.[53] Researchers in one study sounded a cautionary note when they found that coadministration of coenzyme Q10 and radiation therapy decreased the effectiveness of the radiotherapy.[54] In this study, mice inoculated with human small cell lung cancer cells (a xenograft study), and then given coenzyme Q10 and single-dose radiation therapy, showed substantially less inhibition of tumor growth than mice in the control group that were treated with radiation therapy alone. Since radiation leads to the production of free radicals, and since antioxidants protect against free radical damage, the effect in this study might be explained by coenzyme Q10 acting as an antioxidant. As noted previously (General Information section), there is some evidence from laboratory and animal studies that analogs of coenzyme Q10 may have direct anticancer activity.[12,34]
Human/Clinical Studies
The use of coenzyme Q10 as a treatment for cancer in humans has been investigated in only a limited manner. With the exception of a single randomized trial,[18] which involved 20 patients and tested the ability of coenzyme Q10 to reduce the cardiotoxicity caused by anthracycline drugs, the studies that have been published consist of anecdotal reports, case reports, case series, and uncontrolled clinical studies.[3,16,17,28-30, reviewed in 20,31-33]
In view of the promising results from animal studies, coenzyme Q10 was tested as a protective agent against the cardiac toxicity observed in cancer patients treated with the anthracycline drug doxorubicin. It has been postulated that doxorubicin interferes with energy-generating biochemical reactions that involve coenzyme Q10 in heart muscle mitochondria and that this interference can be overcome by coenzyme Q10 supplementation.[16,52,55] Studies with adults and children, including the aforementioned randomized trial, have confirmed the decrease in cardiac toxicity observed in animal studies.[3,16-18]
The potential of coenzyme Q10 as an adjuvant therapy for cancer has also been explored. In view of observations that blood levels of coenzyme Q10 are frequently reduced in cancer patients,[12,13, reviewed in 30-32] supplementation with this compound has been tested in patients undergoing conventional treatment. An open-label (nonblinded), uncontrolled clinical study in Denmark followed 32 breast cancer patients for 18 months.[28] The disease in these patients had spread to the axillary lymph nodes, and an unreported number had distant metastases. The patients received antioxidant supplementation (vitamin C, vitamin E, and beta-carotene), other vitamins and trace minerals, essential fatty acids, and coenzyme Q10 (at a dose of 90 milligrams per day), in addition to standard therapy (surgery, radiation therapy, and chemotherapy, with or without tamoxifen). The patients were seen every 3 months to monitor disease status (progressive disease or recurrence), and, if there was a suspicion of recurrence, mammography, bone scan, x-ray, or biopsy was performed. The survival rate for the study period was one hundred percent (four deaths were expected). Six patients were reported to show some evidence of remission; however, incomplete clinical data were provided, and information suggestive of remission was presented for only three of the six patients. None of the six patients had evidence of further metastases. For all 32 patients, decreased use of painkillers, improved quality of life, and an absence of weight loss were reported. Whether painkiller use and quality of life were measured objectively (e.g., from pharmacy records and validated questionnaires, respectively) or subjectively (from patient self-reports) was not specified.
In a follow-up study, one of the six patients with a reported remission and a new patient were treated for several months with higher doses of coenzyme Q10 (390 and 300 milligrams per day, respectively).[29] Surgical removal of the primary breast tumor in both patients had been incomplete. After 3 to 4 months of high-level coenzyme Q10 supplementation, both patients appeared to experience complete regression of their residual breast tumors (assessed by clinical examination and mammography). It should be noted that a different patient identifier was used in the follow-up study for the patient who had participated in the original study. Therefore, it is impossible to determine which of the six patients with a reported remission took part in the follow-up study. In the follow-up study report, the researchers noted that all 32 patients from the original study remained alive at 24 months of observation, whereas six deaths had been expected.[29]
In another report by the same investigators, three breast cancer patients were followed for a total of 3 to 5 years on high-dose coenzyme Q10 (390 milligrams per day).[30] One patient had complete remission of liver metastases (determined by clinical examination and ultrasonography), another had remission of a tumor that had spread to the chest wall (determined by clinical examination and chest X-ray), and the third patient had no microscopic evidence of remaining tumor after a mastectomy (determined by biopsy of the tumor bed).
All three of the above-mentioned human studies [28-30] had important design flaws that could have influenced their outcome. Study weaknesses include the absence of a control group (i.e., all patients received coenzyme Q10), possible selection bias in the follow-up investigations, and multiple confounding variables (i.e., the patients received a variety of supplements in addition to coenzyme Q10, and they received standard therapy either during or immediately before supplementation with coenzyme Q10). Thus, it is impossible to determine whether any of the beneficial results was directly related to coenzyme Q10 therapy.
Anecdotal reports of coenzyme Q10 lengthening the survival of patients with pancreatic, lung, rectal, laryngeal, colon, and prostate cancers also exist in the peer-reviewed, scientific literature.[17] The patients described in these reports also received therapies other than coenzyme Q10, including chemotherapy, radiation therapy, and surgery.
Adverse Effects
No serious toxicity associated with the use of coenzyme Q10 has been reported.[reviewed in 2,4,33,56] Doses of 100 milligrams per day or higher have caused mild insomnia in some individuals.[reviewed in 2] Liver enzyme elevation has been detected in patients taking doses of 300 milligrams per day for extended periods of time, but no liver toxicity has been reported.[reviewed in 2] Researchers in one cardiovascular study reported that coenzyme Q10 caused rashes, nausea, and epigastric (upper abdominal) pain that required withdrawal of a small number of patients from the study.[15] Other reported side effects have included dizziness, photophobia (abnormal visual sensitivity to light), irritability,[15] headache, heartburn, and fatigue.[57]
Certain lipid-lowering drugs, such as the "statins" (lovastatin, pravastatin, and simvastatin) and gemfibrozil, as well as oral agents that lower blood sugar, such as glyburide and tolazamide, cause a decrease in serum levels of coenzyme Q10 and reduce the effects of coenzyme Q10 supplementation.[58,59, reviewed in 2,60] Beta-blockers (drugs that slow the heart rate and lower blood pressure) can inhibit coenzyme Q10-dependent enzyme reactions.[reviewed in 2] The contractile force of the heart in patients with high blood pressure can be increased by coenzyme Q10 administration.[reviewed in 2] Coenzyme Q10 can reduce the body's response to the anticoagulant drug warfarin.[reviewed in 60] Finally, coenzyme Q10 can decrease insulin requirements in individuals with diabetes.[reviewed in 60]
Overall Level of Evidence for Coenzyme Q10
To assist readers in evaluating the results of human studies of CAM treatments for cancer, the strength of the evidence (i.e., the "levels of evidence") associated with each type of treatment is provided whenever possible. To qualify for a levels of evidence analysis, a study must 1) be published in a peer-reviewed, scientific journal; 2) report on a therapeutic outcome(s), such as tumor response, improvement in survival, or measured improvement in quality of life; and 3) describe clinical findings in sufficient detail that a meaningful evaluation can be made. Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. A table showing the levels of evidence scores for qualifying human studies cited in this summary is presented below. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, please click on the following link: Levels of Evidence Analysis for Human Studies of Cancer Complementary and Alternative Medicine.
Coenzyme Q10 Summary: Reference Numbers and the Corresponding Levels of Evidence
Reference Number Statistical Strength of Study Design Strength of Endpoints Measured Combined Score
28 3iii Nonconsecutive Case Series Diii Indirect Surrogates -- Tumor Response Rate 3iiiDiii
References:
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12. Folkers K: The potential of coenzyme Q10 (NSC-140865) in cancer treatment. Cancer Chemotherapy Reports 4(4): 19-22, 1974.
13. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochemical and Biophysical Research Communications 234(2): 296-299, 1997.
14. Jolliet P, Simon N, Barre J, et al.: Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. International Journal of Clinical Pharmacology and Therapeutics 36(9): 506- 509, 1998.
15. Baggio E, Gandini R, Plancher AC, et al.: Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. Molecular Aspects of Medicine 15(suppl): S287-S294, 1994.
16. Cortes EP, Gupta M, Chou C, et al.: Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treatment Reports 62(6): 887-891, 1978.
17. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochemical and Biophysical Research Communications 192(1): 241-245, 1993.
18. Iarussi D, Auricchio U, Agretto A, et al.: Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Molecular Aspects of Medicine 15(suppl): S207-S212, 1994.
19. Folkers K, Shizukuishi S, Takemura K, et al.: Increase in levels of IgG in serum of patients treated with coenzyme Q10. Research Communications in Chemical Pathology and Pharmacology 38(2): 335-338, 1982.
20. Complementary treatments highlighted at recent meeting. Oncology (Huntington NY) 13(2): 166, 1999.
21. Bliznakov E, Casey A, Premuzic E: Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26(9): 253-254, 1970.
22. Folkers K, Hanioka T, Xia LJ, et al.: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochemical and Biophysical Research Communications 176(2): 786-791, 1991.
23. Kawase I, Niitani H, Saijo N, et al.: Enhancing effect of coenzyme Q10 on immunorestoration with Mycobacterium bovis BCG in tumor- bearing mice. Gann 69(4): 493-497, 1978.
24. Bliznakov EG. Effect of stimulation of the host defense system by coenzyme Q10 on dibenzpyrene-induced tumors and infection with friend leukemia virus in mice. Proceedings of the National Academy of Sciences USA 70(2): 390-394, 1973.
25. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathologia et Microbiologia 38: 393-410, 1972.
26. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y: Biomedical and Clinical Aspects of Coenzyme Q. Amsterdam, The Netherlands: Elsevier/North-Holland Biomedical Press, 1977: pp 73-83.
27. Barbieri B, Lund B, Lundstrom B, et al.: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers -- a single blind placebo-controlled and randomized clinical study. BioFactors 9(2-4): 351-357, 1999.
28. Lockwood K, Moesgaard S, Hanioka T, et al.: Apparent partial remission of breast cancer in "high risk" patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molecular Aspects of Medicine 15(suppl): S231-S240, 1994.
29. Lockwood K, Moesgaard S, Folkers K: Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochemical and Biophysical Research Communications 199(3): 1504-1508, 1994.
30. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochemical and Biophysical Research Communications 212(1): 172-177, 1995.
31. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochemical and Biophysical Research Communications 224(2): 358-361, 1996.
32. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Progress in Drug Research 48: 147-171, 1997.
33. Hodges S, Hertz, Lockwood K, et al.: CoQ10: could it have a role in cancer management? BioFactors 9(2-4): 365-370, 1999.
34. Folkers K, Porter TH, Bertino JR, et al.: Inhibition of two human tumor cell lines by antimetabolites of coenzyme Q10. Research Communications in Chemical Pathology and Pharmacology 19(3): 485-490, 1978.
35. Chipperfield B: Ubiquinone concentrations in tumours and some normal tissues in man. Nature 209(5029): 1207-1209, 1966.
36. Eggens I, Elmberger PG, Low P, et al.: Polyisoprenoid, cholesterol and ubiquinone levels in human hepatocellular carcinomas. British Journal of Experimental Pathology 70(1): 83-92, 1989.
37. Mano T, Iwase K, Hayashi R, et al.: Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders. American Journal of the Medical Sciences 315(4): 230-232, 1998.
38. Picardo M, Grammatico P, Roccella F, et al.: Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma. Journal of Investigative Dermatology 107(3): 322-326, 1996.
39. Portakal O, Ozkaya O, Inal ME, et al.: Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clinical Biochemistry 33(4): 279-284, 2000.
40. Shaw M, Ray P, Rubenstein M, et al.: Lymphocyte subsets in urologic cancer patients. Urological Research 15(3): 181-185, 1987.
41. Tsuyuguchi I, Shiratsuchi H, Fukuoka M: T-lymphocyte subsets in primary lung cancer. Japanese Journal of Clinical Oncology 17(1): 13-17, 1987.
42. Aust AE, Eveleigh JF: Mechanisms of DNA oxidation. Proceedings of the Society for Experimental Biology and Medicine 222(3): 246-252, 1999.
43. Halliwell B: Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutation Research 443(1-2): 37-52, 1999.
44. Burcham PC: Internal hazards: baseline DNA damage by endogenous products of normal metabolism. Mutation Research 443(1-2): 11-36, 1999.
45. Dreher D, Junod AF: Role of oxygen free radicals in cancer development. European Journal of Cancer 32A(1): 30-38, 1996.
46. Ludwig FC, Elashoff RM, Smith JL, et al.: Response of the bone marrow of the vitamin E-deficient rabbit to coenzyme Q and vitamin E. Scandanavian Journal of Haematology 4(4): 292-300, 1967.
47. Choe JY, Combs AB, Folkers K: Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats. Research Communications in Chemical Pathology and Pharmacology 23(1): 199-202, 1979.
48. Combs AB, Choe JY, Truong DH, et al.: Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice. Research Communications in Chemical Pathology and Pharmacology 18(3): 565-568, 1977.
49. Folkers K, Choe JY, Combs AB: Rescue by coenzyme Q10 from electrocardiographic abnormalities caused by the toxicity of adriamycin in the rat. Proceedings of the National Academy of Sciences of the United States 75(10): 5178-5180, 1976.
50. Lubawy WC, Dallam RA, Hurley LH: Protection against anthramycin- induced toxicity in mice by coenzyme Q10. Journal of the National Cancer Institute 64(1): 105-109, 1980.
51. Shinozawa S, Gomita Y, Araki Y: Protective effects of various drugs on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice and rats. Biological and Pharmaceutical Bulletin 16(11): 1114-1117, 1993.
52. Usui T, Ishikura H, Izumi Y, et al.: Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicology Letters 12(1), 1982.
53. Shaeffer J, El-Mahdi AM, Nichols RK: Coenzyme Q10 and adriamycin toxicity in mice. Research Communications in Chemical Pathology and Pharmacology 29(2): 309-315, 1980.
54. Lund EL, Quistorff B, Spang-Thomsen M, et al.: Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiologica 43(5): 505-506, 1998.
55. Iwamoto Y, Hansen IL, Porter TH, et al.: Inhibition of coenzyme Q10-enzymes, succinoxidase and NADH-oxidase, by adriamycin and other quinones having antitumor activity. Biochemical and Biophysical Research Communications 58(3): 633-638, 1974.
56. Heller JH: Disease, the host defense, and Q-10. Perspectives in Biology and Medicine 16(2): 181-187, 1973.
57. Feigin A, Kieburtz K, Como P, et al.: Assessment of coenzyme Q10 tolerability in Huntington's Disease. Movement Disorders 11(3): 321-323, 1996.
58. Kaikkonen J, Nyyssonen K, Tuomainen TP, et al.: Determinants of plasma coenzyme Q10 in humans. Federation of European Biochemical Societies Letters 443(2): 163-166, 1999.
59. Thibault A, Samid D, Tompkins AC, et al.: Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer. Clinical Cancer Research 2(3): 483-491, 1996.
60. Editor's of Pharmacist's Letter/Prescriber's Letter: Coenzyme Q10. In: Natural Medicines Comprehensive Database. Stockton, CA: Therapeutic Research Faculty, 1999: 241-242.
http://www.cancer.gov/cancer_information/doc.aspx?viewid=0E5B4097-610C-4A49-844F-D935F1D7BB07#6
Coenzyme Q10 (PDQ®)
Updated: 05/01/2002
Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Overall Level Of Evidence for Coenzyme Q10
References
For More Information
Overview
This complementary and alternative medicine (CAM) information summary provides an overview of the use of coenzyme Q10 in cancer therapy. The summary includes a history of coenzyme Q10 research, a review of laboratory studies, and data from investigations involving human subjects. Although several naturally occurring forms of coenzyme Q have been identified, Q10 is the predominant form found in humans and most mammals, and it is the form most studied for therapeutic potential. Thus, it will be the only form of coenzyme Q discussed in this summary. Many of the medical and scientific terms used in the summary are hypertext linked (at first use only) to the Cancer.gov Dictionary, which is oriented toward non-experts. When a linked term is clicked, a definition will appear in a separate window. All linked terms and their corresponding definitions will appear as a glossary in the printable version of the summary.
This summary contains the following key information:
· Coenzyme Q10 is made naturally by the human body.
· Coenzyme Q10 helps cells to produce energy, and it acts as an antioxidant.
· Coenzyme Q10 has shown an ability to stimulate the immune system and to protect the heart from damage caused by certain chemotherapy drugs.
· Low blood levels of coenzyme Q10 have been detected in patients with some types of cancer.
· No report of a randomized clinical trial of coenzyme Q10 as a treatment for cancer has been published in a peer-reviewed, scientific journal.
· Coenzyme Q10 is marketed in the United States as a dietary supplement.
General Information
Coenzyme Q10 (also known as Co Q10, Q10, vitamin Q10, ubiquinone, or ubidecarenone) is a benzoquinone compound synthesized naturally by the human body. The "Q" and the "10" in the name refer to the quinone chemical group and the 10 isoprenyl chemical subunits, respectively, that are part of this compound's structure. The term "coenzyme" denotes it as an organic (contains carbon atoms), nonprotein molecule necessary for the proper functioning of its protein partner (an enzyme or an enzyme complex). Coenzyme Q10 is used by cells of the body in a process known variously as aerobic respiration, aerobic metabolism, oxidative metabolism, or cell respiration. Through this process, energy for cell growth and maintenance is created inside cells in compartments called mitochondria.[reviewed in 1-4] Coenzyme Q10 is also used by the body as an endogenous antioxidant.[reviewed in 1,2,4,5,7-9] An antioxidant is a substance that protects cells from free radicals, which are highly reactive chemicals, often containing oxygen atoms, capable of damaging important cellular components such as DNA and lipids. In addition, the plasma level of coenzyme Q10 has been used, in studies, as a measure of oxidative stress (a situation in which normal antioxidant levels are reduced).[10,11]
Coenzyme Q10 is present in most tissues, but the highest concentrations are found in the heart, the liver, the kidneys, and the pancreas.[6] The lowest concentration is found in the lungs.[6] Tissue levels of this compound decrease as people age, due to increased requirements, decreased production,[6] or insufficient intake of the chemical precursors needed for synthesis.[reviewed in 12] In humans, normal blood levels of coenzyme Q10 have been defined variably, with reported values ranging from 0.30 to 3.84 micrograms per milliliter.[13,14,reviewed in 2,4]
Given the importance of coenzyme Q10 to optimal cellular energy production, use of this compound as a treatment for diseases other than cancer has been explored. Most of these investigations have focused on coenzyme Q10 as a treatment for cardiovascular disease.[15,reviewed in 2,4] In patients with cancer, coenzyme Q10 has been shown to protect the heart from anthracycline-induced cardiotoxicity (anthracyclines are a family of chemotherapy drugs, including doxorubicin, that have the potential to damage the heart)[3,16-18] and to stimulate the immune system.[19, reviewed in 20] Stimulation of the immune system by this compound has also been observed in animal studies and in humans without cancer.[21-27] In part because of its immunostimulatory potential, coenzyme Q10 has been used as an adjuvant therapy in patients with various types of cancer.[17,28,29,30, reviewed in 20,31-33]
While coenzyme Q10 may show indirect anticancer activity through its effect(s) on the immune system, there is evidence to suggest that analogs of this compound can suppress cancer growth directly. Analogs of coenzyme Q10 have been shown to inhibit the proliferation of cancer cells in vitro and the growth of cancer cells transplanted into rats and mice.[12,34] In view of these findings, it has been proposed that analogs of coenzyme Q10 may function as antimetabolites to disrupt normal biochemical reactions that are required for cell growth and/or survival and, thus, that they may be useful for short periods of time as chemotherapeutic agents.[12,34]
Several companies distribute coenzyme Q10 as a dietary supplement. In the United States, dietary supplements are regulated as foods not drugs. Therefore, premarket evaluation and approval by the Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, there may be considerable variation from lot to lot.
To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. The IND application process is highly confidential, and IND information can be disclosed only by the applicants. To date, no investigators have announced that they have applied for an IND to study coenzyme Q10 as a treatment for cancer.
In animal studies, coenzyme Q10 has been administered by injection (intravenous, intraperitoneal, intramuscular, or subcutaneous). In humans, it is usually taken orally as a pill (tablet or capsule), but intravenous infusions have been given.[4] Coenzyme Q10 is absorbed best with fat; therefore, lipid preparations are better absorbed than the purified compound.[reviewed in 2,4] In human studies, supplementation doses and administration schedules have varied, but usually have been in the range of 90 to 390 milligrams per day.
History
Coenzyme Q10 was first isolated in 1957,[reviewed in 2] and its chemical structure (benzoquinone compound) was determined in 1958.[reviewed in 13] Interest in coenzyme Q10 as a therapeutic agent in cancer began in 1961, when a deficiency was noted in the blood of both Swedish and American cancer patients, especially in the blood of patients with breast cancer.[13, reviewed in 30,32] A subsequent study showed a statistically significant relationship between the level of plasma coenzyme Q10 deficiency and breast cancer prognosis.[14] Low blood levels of this compound have been reported in patients with malignancies other than breast cancer, including myeloma, lymphoma, and cancers of the lung, prostate, pancreas, colon, kidney, and head and neck.[12,13 reviewed in 31] Furthermore, decreased levels of coenzyme Q10 have been detected in malignant human tissue,[35-39] but increased levels have been reported as well.[35]
A large amount of laboratory and animal data on coenzyme Q10 has accumulated since 1962.[reviewed in 13] Research into cellular energy producing mechanisms that involve this compound was awarded the Nobel Prize in chemistry in 1978. Some of the accumulated data show that coenzyme Q10 stimulates animal immune systems, leading to higher antibody levels,[21] greater numbers and/or activities of macrophages and T cells (T lymphocytes),[21,23] and increased resistance to infection.[24-26] Coenzyme Q10 has also been reported to increase IgG (immunoglobulin G) antibody levels and to increase the CD4 to CD8 T-cell ratio in humans.[19,22,27] CD4 and CD8 are proteins found on the surface of T cells, with CD4 and CD8 identifying "helper" T cells and "cytotoxic" T cells, respectively; decreased CD4 to CD8 T-cell ratios have been reported for cancer patients.[40,41] Research subsequently delineated the antioxidant properties of coenzyme Q10.[10,11, reviewed in1,4,6]
Proposed mechanisms of action for coenzyme Q10 that are relevant to cancer include its essential function in cellular energy production and its stimulation of the immune system (the two of which may be related), as well as its role as an antioxidant. Coenzyme Q10 is essential to aerobic energy production,[reviewed in 1-3] and it has been suggested that increased cellular energy may lead to increased antibody synthesis in B cells (B lymphocytes).[12,19] As noted previously (General Information section), coenzyme Q10 can also behave as an antioxidant.[reviewed in 1,2,4-9] In this capacity, coenzyme Q10 is thought to stabilize cell membranes (lipid-containing structures essential to maintaining cell integrity) and to prevent free radical damage to other important cellular components.[reviewed in 1,2,6,9] Free radical damage to DNA (and possibly to other cellular molecules) may be a factor in cancer development.[reviewed in 7,10,38,42-45]
Laboratory/Animal/Preclinical Studies
Laboratory work on coenzyme Q10 has focused primarily on its structure and its function in cell respiration. Studies in animals have demonstrated that coenzyme Q10 is capable of stimulating the immune system, with treated animals showing increased resistance to protozoal infections [25,26] and to viral and chemically induced neoplasia.[24-26, reviewed in 13] Early studies of coenzyme Q10 showed increased hematopoiesis (the formation of new blood cells) in monkeys,[reviewed in 13,17] rabbits,[46] and poultry.[reviewed in 17] Coenzyme Q10 demonstrated a protective effect on the heart muscle of mice, rats, and rabbits given the anthracycline anticancer drug doxorubicin.[47-52] Although another study confirmed this protective effect with intraperitoneal administration of doxorubicin in mice, it failed to demonstrate a protective effect when the anthracycline was given intravenously, which is the route of administration in humans.[53] Researchers in one study sounded a cautionary note when they found that coadministration of coenzyme Q10 and radiation therapy decreased the effectiveness of the radiotherapy.[54] In this study, mice inoculated with human small cell lung cancer cells (a xenograft study), and then given coenzyme Q10 and single-dose radiation therapy, showed substantially less inhibition of tumor growth than mice in the control group that were treated with radiation therapy alone. Since radiation leads to the production of free radicals, and since antioxidants protect against free radical damage, the effect in this study might be explained by coenzyme Q10 acting as an antioxidant. As noted previously (General Information section), there is some evidence from laboratory and animal studies that analogs of coenzyme Q10 may have direct anticancer activity.[12,34]
Human/Clinical Studies
The use of coenzyme Q10 as a treatment for cancer in humans has been investigated in only a limited manner. With the exception of a single randomized trial,[18] which involved 20 patients and tested the ability of coenzyme Q10 to reduce the cardiotoxicity caused by anthracycline drugs, the studies that have been published consist of anecdotal reports, case reports, case series, and uncontrolled clinical studies.[3,16,17,28-30, reviewed in 20,31-33]
In view of the promising results from animal studies, coenzyme Q10 was tested as a protective agent against the cardiac toxicity observed in cancer patients treated with the anthracycline drug doxorubicin. It has been postulated that doxorubicin interferes with energy-generating biochemical reactions that involve coenzyme Q10 in heart muscle mitochondria and that this interference can be overcome by coenzyme Q10 supplementation.[16,52,55] Studies with adults and children, including the aforementioned randomized trial, have confirmed the decrease in cardiac toxicity observed in animal studies.[3,16-18]
The potential of coenzyme Q10 as an adjuvant therapy for cancer has also been explored. In view of observations that blood levels of coenzyme Q10 are frequently reduced in cancer patients,[12,13, reviewed in 30-32] supplementation with this compound has been tested in patients undergoing conventional treatment. An open-label (nonblinded), uncontrolled clinical study in Denmark followed 32 breast cancer patients for 18 months.[28] The disease in these patients had spread to the axillary lymph nodes, and an unreported number had distant metastases. The patients received antioxidant supplementation (vitamin C, vitamin E, and beta-carotene), other vitamins and trace minerals, essential fatty acids, and coenzyme Q10 (at a dose of 90 milligrams per day), in addition to standard therapy (surgery, radiation therapy, and chemotherapy, with or without tamoxifen). The patients were seen every 3 months to monitor disease status (progressive disease or recurrence), and, if there was a suspicion of recurrence, mammography, bone scan, x-ray, or biopsy was performed. The survival rate for the study period was one hundred percent (four deaths were expected). Six patients were reported to show some evidence of remission; however, incomplete clinical data were provided, and information suggestive of remission was presented for only three of the six patients. None of the six patients had evidence of further metastases. For all 32 patients, decreased use of painkillers, improved quality of life, and an absence of weight loss were reported. Whether painkiller use and quality of life were measured objectively (e.g., from pharmacy records and validated questionnaires, respectively) or subjectively (from patient self-reports) was not specified.
In a follow-up study, one of the six patients with a reported remission and a new patient were treated for several months with higher doses of coenzyme Q10 (390 and 300 milligrams per day, respectively).[29] Surgical removal of the primary breast tumor in both patients had been incomplete. After 3 to 4 months of high-level coenzyme Q10 supplementation, both patients appeared to experience complete regression of their residual breast tumors (assessed by clinical examination and mammography). It should be noted that a different patient identifier was used in the follow-up study for the patient who had participated in the original study. Therefore, it is impossible to determine which of the six patients with a reported remission took part in the follow-up study. In the follow-up study report, the researchers noted that all 32 patients from the original study remained alive at 24 months of observation, whereas six deaths had been expected.[29]
In another report by the same investigators, three breast cancer patients were followed for a total of 3 to 5 years on high-dose coenzyme Q10 (390 milligrams per day).[30] One patient had complete remission of liver metastases (determined by clinical examination and ultrasonography), another had remission of a tumor that had spread to the chest wall (determined by clinical examination and chest X-ray), and the third patient had no microscopic evidence of remaining tumor after a mastectomy (determined by biopsy of the tumor bed).
All three of the above-mentioned human studies [28-30] had important design flaws that could have influenced their outcome. Study weaknesses include the absence of a control group (i.e., all patients received coenzyme Q10), possible selection bias in the follow-up investigations, and multiple confounding variables (i.e., the patients received a variety of supplements in addition to coenzyme Q10, and they received standard therapy either during or immediately before supplementation with coenzyme Q10). Thus, it is impossible to determine whether any of the beneficial results was directly related to coenzyme Q10 therapy.
Anecdotal reports of coenzyme Q10 lengthening the survival of patients with pancreatic, lung, rectal, laryngeal, colon, and prostate cancers also exist in the peer-reviewed, scientific literature.[17] The patients described in these reports also received therapies other than coenzyme Q10, including chemotherapy, radiation therapy, and surgery.
Adverse Effects
No serious toxicity associated with the use of coenzyme Q10 has been reported.[reviewed in 2,4,33,56] Doses of 100 milligrams per day or higher have caused mild insomnia in some individuals.[reviewed in 2] Liver enzyme elevation has been detected in patients taking doses of 300 milligrams per day for extended periods of time, but no liver toxicity has been reported.[reviewed in 2] Researchers in one cardiovascular study reported that coenzyme Q10 caused rashes, nausea, and epigastric (upper abdominal) pain that required withdrawal of a small number of patients from the study.[15] Other reported side effects have included dizziness, photophobia (abnormal visual sensitivity to light), irritability,[15] headache, heartburn, and fatigue.[57]
Certain lipid-lowering drugs, such as the "statins" (lovastatin, pravastatin, and simvastatin) and gemfibrozil, as well as oral agents that lower blood sugar, such as glyburide and tolazamide, cause a decrease in serum levels of coenzyme Q10 and reduce the effects of coenzyme Q10 supplementation.[58,59, reviewed in 2,60] Beta-blockers (drugs that slow the heart rate and lower blood pressure) can inhibit coenzyme Q10-dependent enzyme reactions.[reviewed in 2] The contractile force of the heart in patients with high blood pressure can be increased by coenzyme Q10 administration.[reviewed in 2] Coenzyme Q10 can reduce the body's response to the anticoagulant drug warfarin.[reviewed in 60] Finally, coenzyme Q10 can decrease insulin requirements in individuals with diabetes.[reviewed in 60]
Overall Level of Evidence for Coenzyme Q10
To assist readers in evaluating the results of human studies of CAM treatments for cancer, the strength of the evidence (i.e., the "levels of evidence") associated with each type of treatment is provided whenever possible. To qualify for a levels of evidence analysis, a study must 1) be published in a peer-reviewed, scientific journal; 2) report on a therapeutic outcome(s), such as tumor response, improvement in survival, or measured improvement in quality of life; and 3) describe clinical findings in sufficient detail that a meaningful evaluation can be made. Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. A table showing the levels of evidence scores for qualifying human studies cited in this summary is presented below. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, please click on the following link: Levels of Evidence Analysis for Human Studies of Cancer Complementary and Alternative Medicine.
Coenzyme Q10 Summary: Reference Numbers and the Corresponding Levels of Evidence
Reference Number Statistical Strength of Study Design Strength of Endpoints Measured Combined Score
28 3iii Nonconsecutive Case Series Diii Indirect Surrogates -- Tumor Response Rate 3iiiDiii
References:
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4. Overvad K, Diamant B, Holm L, et al.: Coenzyme Q10 in health and disease. European Journal of Clinical Nutrition 53(10): 764-770, 1999.
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7. Gordon MH: Dietary antioxidants in disease prevention. Natural Product Reports 13(4): 265-273, 1996.
8. Palazzoni G, Pucello D, Littarru GP, et al.: Coenzyme Q10 and colorectal neoplasms in aged patients. Rays 22(suppl 1): 73-76, 1997.
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10. Yamamoto Y, Yamashita S, Fujisawa A, et al.: Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochemical and Biophysical Research Communications 247(1): 166-170, 1998.
11. Yamamoto Y, Yamashita S: Plasma ratio of ubiquinol and ubiquinone as a marker of oxidative stress. Molecular Aspects of Medicine 18 (suppl): S79- S84, 1997.
12. Folkers K: The potential of coenzyme Q10 (NSC-140865) in cancer treatment. Cancer Chemotherapy Reports 4(4): 19-22, 1974.
13. Folkers K, Osterborg A, Nylander M, et al.: Activities of vitamin Q10 in animal models and a serious deficiency in patients with cancer. Biochemical and Biophysical Research Communications 234(2): 296-299, 1997.
14. Jolliet P, Simon N, Barre J, et al.: Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. International Journal of Clinical Pharmacology and Therapeutics 36(9): 506- 509, 1998.
15. Baggio E, Gandini R, Plancher AC, et al.: Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure. Molecular Aspects of Medicine 15(suppl): S287-S294, 1994.
16. Cortes EP, Gupta M, Chou C, et al.: Adriamycin cardiotoxicity: early detection by systolic time interval and possible prevention by coenzyme Q10. Cancer Treatment Reports 62(6): 887-891, 1978.
17. Folkers K, Brown R, Judy WV, et al.: Survival of cancer patients on therapy with coenzyme Q10. Biochemical and Biophysical Research Communications 192(1): 241-245, 1993.
18. Iarussi D, Auricchio U, Agretto A, et al.: Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. Molecular Aspects of Medicine 15(suppl): S207-S212, 1994.
19. Folkers K, Shizukuishi S, Takemura K, et al.: Increase in levels of IgG in serum of patients treated with coenzyme Q10. Research Communications in Chemical Pathology and Pharmacology 38(2): 335-338, 1982.
20. Complementary treatments highlighted at recent meeting. Oncology (Huntington NY) 13(2): 166, 1999.
21. Bliznakov E, Casey A, Premuzic E: Coenzymes Q: stimulants of the phagocytic activity in rats and immune response in mice. Experientia 26(9): 253-254, 1970.
22. Folkers K, Hanioka T, Xia LJ, et al.: Coenzyme Q10 increases T4/T8 ratios of lymphocytes in ordinary subjects and relevance to patients having the AIDS related complex. Biochemical and Biophysical Research Communications 176(2): 786-791, 1991.
23. Kawase I, Niitani H, Saijo N, et al.: Enhancing effect of coenzyme Q10 on immunorestoration with Mycobacterium bovis BCG in tumor- bearing mice. Gann 69(4): 493-497, 1978.
24. Bliznakov EG. Effect of stimulation of the host defense system by coenzyme Q10 on dibenzpyrene-induced tumors and infection with friend leukemia virus in mice. Proceedings of the National Academy of Sciences USA 70(2): 390-394, 1973.
25. Bliznakov EG, Adler AD: Nonlinear response of the reticuloendothelial system upon stimulation. Pathologia et Microbiologia 38: 393-410, 1972.
26. Bliznakov EG: Coenzyme Q in experimental infections and neoplasia. In: Folkers K, Yamamura Y: Biomedical and Clinical Aspects of Coenzyme Q. Amsterdam, The Netherlands: Elsevier/North-Holland Biomedical Press, 1977: pp 73-83.
27. Barbieri B, Lund B, Lundstrom B, et al.: Coenzyme Q10 administration increases antibody titer in hepatitis B vaccinated volunteers -- a single blind placebo-controlled and randomized clinical study. BioFactors 9(2-4): 351-357, 1999.
28. Lockwood K, Moesgaard S, Hanioka T, et al.: Apparent partial remission of breast cancer in "high risk" patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molecular Aspects of Medicine 15(suppl): S231-S240, 1994.
29. Lockwood K, Moesgaard S, Folkers K: Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochemical and Biophysical Research Communications 199(3): 1504-1508, 1994.
30. Lockwood K, Moesgaard S, Yamamoto T, et al.: Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochemical and Biophysical Research Communications 212(1): 172-177, 1995.
31. Folkers K: Relevance of the biosynthesis of coenzyme Q10 and of the four bases of DNA as a rationale for the molecular causes of cancer and a therapy. Biochemical and Biophysical Research Communications 224(2): 358-361, 1996.
32. Ren S, Lien EJ: Natural products and their derivatives as cancer chemopreventive agents. Progress in Drug Research 48: 147-171, 1997.
33. Hodges S, Hertz, Lockwood K, et al.: CoQ10: could it have a role in cancer management? BioFactors 9(2-4): 365-370, 1999.
34. Folkers K, Porter TH, Bertino JR, et al.: Inhibition of two human tumor cell lines by antimetabolites of coenzyme Q10. Research Communications in Chemical Pathology and Pharmacology 19(3): 485-490, 1978.
35. Chipperfield B: Ubiquinone concentrations in tumours and some normal tissues in man. Nature 209(5029): 1207-1209, 1966.
36. Eggens I, Elmberger PG, Low P, et al.: Polyisoprenoid, cholesterol and ubiquinone levels in human hepatocellular carcinomas. British Journal of Experimental Pathology 70(1): 83-92, 1989.
37. Mano T, Iwase K, Hayashi R, et al.: Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with various thyroid disorders. American Journal of the Medical Sciences 315(4): 230-232, 1998.
38. Picardo M, Grammatico P, Roccella F, et al.: Imbalance in the antioxidant pool in melanoma cells and normal melanocytes from patients with melanoma. Journal of Investigative Dermatology 107(3): 322-326, 1996.
39. Portakal O, Ozkaya O, Inal ME, et al.: Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clinical Biochemistry 33(4): 279-284, 2000.
40. Shaw M, Ray P, Rubenstein M, et al.: Lymphocyte subsets in urologic cancer patients. Urological Research 15(3): 181-185, 1987.
41. Tsuyuguchi I, Shiratsuchi H, Fukuoka M: T-lymphocyte subsets in primary lung cancer. Japanese Journal of Clinical Oncology 17(1): 13-17, 1987.
42. Aust AE, Eveleigh JF: Mechanisms of DNA oxidation. Proceedings of the Society for Experimental Biology and Medicine 222(3): 246-252, 1999.
43. Halliwell B: Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutation Research 443(1-2): 37-52, 1999.
44. Burcham PC: Internal hazards: baseline DNA damage by endogenous products of normal metabolism. Mutation Research 443(1-2): 11-36, 1999.
45. Dreher D, Junod AF: Role of oxygen free radicals in cancer development. European Journal of Cancer 32A(1): 30-38, 1996.
46. Ludwig FC, Elashoff RM, Smith JL, et al.: Response of the bone marrow of the vitamin E-deficient rabbit to coenzyme Q and vitamin E. Scandanavian Journal of Haematology 4(4): 292-300, 1967.
47. Choe JY, Combs AB, Folkers K: Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats. Research Communications in Chemical Pathology and Pharmacology 23(1): 199-202, 1979.
48. Combs AB, Choe JY, Truong DH, et al.: Reduction by coenzyme Q10 of the acute toxicity of adriamycin in mice. Research Communications in Chemical Pathology and Pharmacology 18(3): 565-568, 1977.
49. Folkers K, Choe JY, Combs AB: Rescue by coenzyme Q10 from electrocardiographic abnormalities caused by the toxicity of adriamycin in the rat. Proceedings of the National Academy of Sciences of the United States 75(10): 5178-5180, 1976.
50. Lubawy WC, Dallam RA, Hurley LH: Protection against anthramycin- induced toxicity in mice by coenzyme Q10. Journal of the National Cancer Institute 64(1): 105-109, 1980.
51. Shinozawa S, Gomita Y, Araki Y: Protective effects of various drugs on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice and rats. Biological and Pharmaceutical Bulletin 16(11): 1114-1117, 1993.
52. Usui T, Ishikura H, Izumi Y, et al.: Possible prevention from the progression of cardiotoxicity in adriamycin-treated rabbits by coenzyme Q10. Toxicology Letters 12(1), 1982.
53. Shaeffer J, El-Mahdi AM, Nichols RK: Coenzyme Q10 and adriamycin toxicity in mice. Research Communications in Chemical Pathology and Pharmacology 29(2): 309-315, 1980.
54. Lund EL, Quistorff B, Spang-Thomsen M, et al.: Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiologica 43(5): 505-506, 1998.
55. Iwamoto Y, Hansen IL, Porter TH, et al.: Inhibition of coenzyme Q10-enzymes, succinoxidase and NADH-oxidase, by adriamycin and other quinones having antitumor activity. Biochemical and Biophysical Research Communications 58(3): 633-638, 1974.
56. Heller JH: Disease, the host defense, and Q-10. Perspectives in Biology and Medicine 16(2): 181-187, 1973.
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ZINC DEFICIENCY, METAL METABOLISM AND BEHAVIOR DISORDERS
Βy William J. Walsh
INTRODUCTION
Most Americans receive all the zinc they need if they have a reasonably well-balanced diet involving the major food groups. However, many persons are born with a metal-metabolism disorder which results in zinc depletion regardless of diet.
Zinc is a component of more than 80 enzymes. High concentrations have been found in brain hippocampus, and many medical researchers believe that zinc is a neurotransmitter. Low zinc levels at these sites could reduce the inhibition of neuron activity, thus leading to abnormal behavior. The discovery of zinc "finger proteins" in the past decade has led to a vastly improved understanding of how cells replicate and divide. There role in behavior is not yet clear, but could be involved in the transport or availability of zinc. Recent research has shown zinc to be far more important than previously believed and low levels of zinc are associated with behavior disorders.
Many of the patients of the Carl Pfeiffer Treatment Center suffer from behavior disorders. The most common ones are attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), obsessive compulsive disorder (OCD), and conduct disorder (CD). These patients typically have a history of extensive counseling and multiple medications and many have experienced residential care. They represent a narrow and rather uncharacteristic segment of the general population.
A high percentage of behavior disordered persons exhibit abnormal levels of copper, zinc, lead, cadmium, calcium, magnesium and manganese in blood, urine, and tissues, based on chemical analysis results from thousands of patients. With regard to zinc, this condition appears to involve a malfunction of the metal-binding protein metallothionein. Most of these patients have symptoms of zinc deficiency along with depressed levels of zinc in their blood plasma.
The high incidence of zinc deficiency in assaultive young males was illustrated in a recent study1 which found elevated serum copper and depressed plasma zinc concentration, compared to normal controls. This study confirmed our clinical observations of zinc depletion in more than 4,000 behavior disordered patients.
Our clinical observations and research have indicated that the copper/zinc ratio appears to be more decisively important than either of the individual metals alone. Zinc deficiency often results in elevated blood levels of copper, due to the dynamic competition of these metals in the body. Elevated blood copper has been associated with episodic violence, hyperactivity, learning disabilities, and depression.
DIAGNOSIS OF ZINC DEFICIENCY
Zinc deficiency is difficult to diagnose since no single laboratory test or combination of tests is decisive in every case. For example, blood levels are sometimes normal in zinc deficient persons due to homeostasis. Urine and hair tissue levels are often elevated in zinc deficiency because of "short circuiting" of zinc through the body and high rates of excretion.
The two principal factors which lead our Center's physicians to a diagnosis of zinc deficiency are: 1) depressed plasma zinc, and 2) presence of clinical symptoms of zinc depletion which are alleviated by zinc supplementation2, 3, 4, 5, 6, and 7. Since zinc tolerance tests show plasma levels to be affected for 6 hours following zinc supplementation8 and 9, zinc supplements are avoided for 24 hours prior to sampling of plasma.
The clinical symptoms associated with zinc deficiency or depletion include the following:
* Eczema, acne, and/or psoriasis10, 11, 12, 13, and 14,
* Poor wound healing, including leg ulcers and oral lesions15 and 16,
* Lines of Beau on the fingernails17,
* Growth retardation18, 19, 20, and 21,
* Delayed sexual maturation22,
* Hypogeusia or poor taste acuity23 and 24, and
* Chronic immunodeficiency and frequent infections25 and 26.
A "working diagnosis" of zinc deficiency can be made if clinical symptoms of zinc deficiency are clearly evident from the initial physical examination and medical history. Usually more than one or the above symptoms are present in zinc deficiency. This initial diagnosis is later supported or negated by laboratory analysis for plasma zinc along with observed response (or non-response) to zinc supplementation.
The Carl Pfeiffer Treatment Center generally retests plasma zinc and evaluates symptoms after 4-6 months of treatment to determine if dosages need adjustment.
TREATMENT OF ZINC DEPLETION
Zinc depletion is corrected by supplementation with zinc (picolinate or gluconate) along with augmenting nutrients including L-cysteine, pyridoxine, ascorbic acid, and vitamin E. Manganese is also useful in promoting proper metallothionein function. If copper levels are elevated, effective treatment must also enhance the release of copper from tissues and copper excretion. L-cysteine helps mobilize and excrete copper while enhancing zinc absorption. Correction of zinc deficiency is best accomplished under the care of a physician or nutritionist who is experienced in metal metabolism disorders. Indiscriminant dosages of zinc to persons who do not need it can cause anemia and imbalanced trace metals.
Treatment of mild or moderate zinc depletion can take months to complete. Some cases of severe zinc depletion require a year or more to resolve. Achievement of a proper zinc balance is slowed by growth spurts, injury, illness, or severe stress. In addition, persons with malabsorption or Type A blood respond to treatment more slowly.
DISCUSSION
We find that zinc deficient individuals usually respond well to inexpensive supplementation with zinc and augmenting nutrients. Many patients who previously experienced years of counseling, psychotherapy, aggressive medication programs, and/or residential treatment become greatly improved and respond to less intensive (and less expensive) therapies. Zinc deficiency can be corrected, but not cured. If treatment is discontinued, the prior zinc deficiency will reemerge with all symptoms gradually returning. Zinc deficiency, like diabetes, requires life long treatment. Fortunately, it is a simple, low cost, safe treatment.
The Center involves the collaboration of biochemists and medical doctors. We believe that this coupling of disciplines provides an ideal capability for biochemical evaluation and medical treatment.
REFERENCES:
1. Walsh, W.J., Isaacson, H.R., Rahman, F., Hall, A., and Young, I.J., "Elevated blood copper:zinc ratios in assaultive young males", Neuroscience Annual Meeting, Abstract of Papers, Miami Beach, 1994 (In Print).
2. Cunnane, S.C., Zinc: Clinical and Biochemical Significance, CRC Press, Inc., Boca Raton, FL (1988).
3. Prasad, A.S., "Deficiency of zinc in man and its toxicity", in Trace Elements in Human Health and Disease, Vol. 1, Academic Press, New York, 1976.
4. Prasad, A.S., "Clinical and biochemical spectrum of zinc deficiency in human subjects", in Current Topics in Nutrition and Disease, Vol 6, New York, 1982.
5. Smith, J.C., Holbrook, J.T., and Danford, D.E., "Analysis and evaluation of zinc and copper in human plasma and serum", J. Amer. College of Nutr., 4:627-638 (1985).
6. Kleimola, V., et al, "The zinc, copper, and iron status in children with chronic diseases", in Trace Element Analytical Chemistry in Medicine and Biology, Walter de Gruyter, New York (1983).
7. Reding, P., DuChateau, J., and Bataille, C., "Oral zinc supplementation improves hepatic encephalopathy", Lancet, ii, 493 (1984).
8. Pohit, J., Saha, K.C., and Pal, B., "A zinc tolerance test", Clin. Chim. Acta, 114: 279 (1981).
9. Pecoud, A., Donzel, P., and Schelling, J.L., "Effects of foodstuffs on the absorption of zinc sulphate", Clin. Pharmacol. Ther., 17, 469 (1975).
10. Molokhia, M.M. and Portnoy, B., "Zinc and copper in dermatology", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1980).
11. Schmidt, K., et.al., "Determination of trace element concentrations in psoriatic and non-psoriatic scales with special attention to zinc", in Trace Element Analytical Chemistry in Medicine and Biology, Vol. 1, Walter de Gruyter, New York (1980).
12. McMillan, E.M., and Rowe, D., "Plasma zinc in psoriasis. Relation to surface area involvement", Br. J. Dermatol., 108, 301 (1983).
13. Ecker, R.J. and Schroeder, A.L., "Acrodermatitis and acquired zinc deficiency", Arch. Dermatol., 114: 937 (1978).
14. Withers, A.F., Baker, H., and Musa, M, "Plasma zinc in psoriasis", Lancet, ii: 278 (1968).
15. Van Rij, A.M., "Zinc supplements in surgery", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1982).
16. Henzel, J.H., et al., "Zinc concentrations within healing wounds: significance of post-operative zincuria on availability and requirements during tissue repair", Arch. Surg., 349: 357 (1970).
17. Weismann, K., "Lines of Beau: Possible markers of zinc deficiency", Acta Dermatol. Venereol., 57: 88 (1977).
18. Collipp, P.J., et al., "Zinc deficiency: Improvement in growth and growth hormone levels with oral zinc therapy", Ann. Nutr. Metab., 26: 287 (1982).
19. Hambridge, K.M., and Walravens, P.A., "Zinc deficiency in infants and preadolescent children", in Trace Elements in Human Health and Disease, Vol. 1, Prasad, A.S. and Oberleas, D., Eds., Academic Press, New York (1976).
20. Golden, B.E. and Golden, M.H.N., "Effect of zinc supplementation on the dietary intake, rate of weight gain and energy cost of tissue deposition in children recovering from severe malnutrition", Am. J. Clin. Nutr., 34: 900 (1981).
21. Laditan, A.O. and Ette, S.I., "Plasma zinc and copper during the acute phase of protein-energy malnutrition (PEM) and after recovery", Trop. Geogr. Med., 34: 77 (1982).
22. Sandstead, H.H., Prasad, A.S., et al., "Human zinc deficiency, endocrine manifestations, and response to treatment", Amer. J. Clin. Nutr., 20:422 (1967).
23. Heinkin, R.I., and Bradley, D.F., "Hypogeusia corrected by nickel and zinc", Life Sci., 9: 701 (1970).
24. Sprenger, K.B.G. et al., "Improvement of uremic neuropathy and hypogeusia by dialysate zinc supplementation: a double-blind study", Kidney Int., Suppl. 16: 5315 (1983).
25. Cunningham-Rundles, C., et al., "Zinc deficiency, depressed thymic hormones and T-lymphocyte dysfunction in patients with hypogammaglobulinemia", Clin. Immunol. Immunopathol., 21: 387 (1981).
26. Good, R.A., et al., "Zinc and immunity", in Clinical, Biochemical, and Nutritional Aspects of Trace Elements, Prasad, A.S. Ed., Alan R. Liss, New York (1982).
Most Americans receive all the zinc they need if they have a reasonably well-balanced diet involving the major food groups. However, many persons are born with a metal-metabolism disorder which results in zinc depletion regardless of diet.
Zinc is a component of more than 80 enzymes. High concentrations have been found in brain hippocampus, and many medical researchers believe that zinc is a neurotransmitter. Low zinc levels at these sites could reduce the inhibition of neuron activity, thus leading to abnormal behavior. The discovery of zinc "finger proteins" in the past decade has led to a vastly improved understanding of how cells replicate and divide. There role in behavior is not yet clear, but could be involved in the transport or availability of zinc. Recent research has shown zinc to be far more important than previously believed and low levels of zinc are associated with behavior disorders.
Many of the patients of the Carl Pfeiffer Treatment Center suffer from behavior disorders. The most common ones are attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), obsessive compulsive disorder (OCD), and conduct disorder (CD). These patients typically have a history of extensive counseling and multiple medications and many have experienced residential care. They represent a narrow and rather uncharacteristic segment of the general population.
A high percentage of behavior disordered persons exhibit abnormal levels of copper, zinc, lead, cadmium, calcium, magnesium and manganese in blood, urine, and tissues, based on chemical analysis results from thousands of patients. With regard to zinc, this condition appears to involve a malfunction of the metal-binding protein metallothionein. Most of these patients have symptoms of zinc deficiency along with depressed levels of zinc in their blood plasma.
The high incidence of zinc deficiency in assaultive young males was illustrated in a recent study1 which found elevated serum copper and depressed plasma zinc concentration, compared to normal controls. This study confirmed our clinical observations of zinc depletion in more than 4,000 behavior disordered patients.
Our clinical observations and research have indicated that the copper/zinc ratio appears to be more decisively important than either of the individual metals alone. Zinc deficiency often results in elevated blood levels of copper, due to the dynamic competition of these metals in the body. Elevated blood copper has been associated with episodic violence, hyperactivity, learning disabilities, and depression.
DIAGNOSIS OF ZINC DEFICIENCY
Zinc deficiency is difficult to diagnose since no single laboratory test or combination of tests is decisive in every case. For example, blood levels are sometimes normal in zinc deficient persons due to homeostasis. Urine and hair tissue levels are often elevated in zinc deficiency because of "short circuiting" of zinc through the body and high rates of excretion.
The two principal factors which lead our Center's physicians to a diagnosis of zinc deficiency are: 1) depressed plasma zinc, and 2) presence of clinical symptoms of zinc depletion which are alleviated by zinc supplementation2, 3, 4, 5, 6, and 7. Since zinc tolerance tests show plasma levels to be affected for 6 hours following zinc supplementation8 and 9, zinc supplements are avoided for 24 hours prior to sampling of plasma.
The clinical symptoms associated with zinc deficiency or depletion include the following:
* Eczema, acne, and/or psoriasis10, 11, 12, 13, and 14,
* Poor wound healing, including leg ulcers and oral lesions15 and 16,
* Lines of Beau on the fingernails17,
* Growth retardation18, 19, 20, and 21,
* Delayed sexual maturation22,
* Hypogeusia or poor taste acuity23 and 24, and
* Chronic immunodeficiency and frequent infections25 and 26.
A "working diagnosis" of zinc deficiency can be made if clinical symptoms of zinc deficiency are clearly evident from the initial physical examination and medical history. Usually more than one or the above symptoms are present in zinc deficiency. This initial diagnosis is later supported or negated by laboratory analysis for plasma zinc along with observed response (or non-response) to zinc supplementation.
The Carl Pfeiffer Treatment Center generally retests plasma zinc and evaluates symptoms after 4-6 months of treatment to determine if dosages need adjustment.
TREATMENT OF ZINC DEPLETION
Zinc depletion is corrected by supplementation with zinc (picolinate or gluconate) along with augmenting nutrients including L-cysteine, pyridoxine, ascorbic acid, and vitamin E. Manganese is also useful in promoting proper metallothionein function. If copper levels are elevated, effective treatment must also enhance the release of copper from tissues and copper excretion. L-cysteine helps mobilize and excrete copper while enhancing zinc absorption. Correction of zinc deficiency is best accomplished under the care of a physician or nutritionist who is experienced in metal metabolism disorders. Indiscriminant dosages of zinc to persons who do not need it can cause anemia and imbalanced trace metals.
Treatment of mild or moderate zinc depletion can take months to complete. Some cases of severe zinc depletion require a year or more to resolve. Achievement of a proper zinc balance is slowed by growth spurts, injury, illness, or severe stress. In addition, persons with malabsorption or Type A blood respond to treatment more slowly.
DISCUSSION
We find that zinc deficient individuals usually respond well to inexpensive supplementation with zinc and augmenting nutrients. Many patients who previously experienced years of counseling, psychotherapy, aggressive medication programs, and/or residential treatment become greatly improved and respond to less intensive (and less expensive) therapies. Zinc deficiency can be corrected, but not cured. If treatment is discontinued, the prior zinc deficiency will reemerge with all symptoms gradually returning. Zinc deficiency, like diabetes, requires life long treatment. Fortunately, it is a simple, low cost, safe treatment.
The Center involves the collaboration of biochemists and medical doctors. We believe that this coupling of disciplines provides an ideal capability for biochemical evaluation and medical treatment.
REFERENCES:
1. Walsh, W.J., Isaacson, H.R., Rahman, F., Hall, A., and Young, I.J., "Elevated blood copper:zinc ratios in assaultive young males", Neuroscience Annual Meeting, Abstract of Papers, Miami Beach, 1994 (In Print).
2. Cunnane, S.C., Zinc: Clinical and Biochemical Significance, CRC Press, Inc., Boca Raton, FL (1988).
3. Prasad, A.S., "Deficiency of zinc in man and its toxicity", in Trace Elements in Human Health and Disease, Vol. 1, Academic Press, New York, 1976.
4. Prasad, A.S., "Clinical and biochemical spectrum of zinc deficiency in human subjects", in Current Topics in Nutrition and Disease, Vol 6, New York, 1982.
5. Smith, J.C., Holbrook, J.T., and Danford, D.E., "Analysis and evaluation of zinc and copper in human plasma and serum", J. Amer. College of Nutr., 4:627-638 (1985).
6. Kleimola, V., et al, "The zinc, copper, and iron status in children with chronic diseases", in Trace Element Analytical Chemistry in Medicine and Biology, Walter de Gruyter, New York (1983).
7. Reding, P., DuChateau, J., and Bataille, C., "Oral zinc supplementation improves hepatic encephalopathy", Lancet, ii, 493 (1984).
8. Pohit, J., Saha, K.C., and Pal, B., "A zinc tolerance test", Clin. Chim. Acta, 114: 279 (1981).
9. Pecoud, A., Donzel, P., and Schelling, J.L., "Effects of foodstuffs on the absorption of zinc sulphate", Clin. Pharmacol. Ther., 17, 469 (1975).
10. Molokhia, M.M. and Portnoy, B., "Zinc and copper in dermatology", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1980).
11. Schmidt, K., et.al., "Determination of trace element concentrations in psoriatic and non-psoriatic scales with special attention to zinc", in Trace Element Analytical Chemistry in Medicine and Biology, Vol. 1, Walter de Gruyter, New York (1980).
12. McMillan, E.M., and Rowe, D., "Plasma zinc in psoriasis. Relation to surface area involvement", Br. J. Dermatol., 108, 301 (1983).
13. Ecker, R.J. and Schroeder, A.L., "Acrodermatitis and acquired zinc deficiency", Arch. Dermatol., 114: 937 (1978).
14. Withers, A.F., Baker, H., and Musa, M, "Plasma zinc in psoriasis", Lancet, ii: 278 (1968).
15. Van Rij, A.M., "Zinc supplements in surgery", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1982).
16. Henzel, J.H., et al., "Zinc concentrations within healing wounds: significance of post-operative zincuria on availability and requirements during tissue repair", Arch. Surg., 349: 357 (1970).
17. Weismann, K., "Lines of Beau: Possible markers of zinc deficiency", Acta Dermatol. Venereol., 57: 88 (1977).
18. Collipp, P.J., et al., "Zinc deficiency: Improvement in growth and growth hormone levels with oral zinc therapy", Ann. Nutr. Metab., 26: 287 (1982).
19. Hambridge, K.M., and Walravens, P.A., "Zinc deficiency in infants and preadolescent children", in Trace Elements in Human Health and Disease, Vol. 1, Prasad, A.S. and Oberleas, D., Eds., Academic Press, New York (1976).
20. Golden, B.E. and Golden, M.H.N., "Effect of zinc supplementation on the dietary intake, rate of weight gain and energy cost of tissue deposition in children recovering from severe malnutrition", Am. J. Clin. Nutr., 34: 900 (1981).
21. Laditan, A.O. and Ette, S.I., "Plasma zinc and copper during the acute phase of protein-energy malnutrition (PEM) and after recovery", Trop. Geogr. Med., 34: 77 (1982).
22. Sandstead, H.H., Prasad, A.S., et al., "Human zinc deficiency, endocrine manifestations, and response to treatment", Amer. J. Clin. Nutr., 20:422 (1967).
23. Heinkin, R.I., and Bradley, D.F., "Hypogeusia corrected by nickel and zinc", Life Sci., 9: 701 (1970).
24. Sprenger, K.B.G. et al., "Improvement of uremic neuropathy and hypogeusia by dialysate zinc supplementation: a double-blind study", Kidney Int., Suppl. 16: 5315 (1983).
25. Cunningham-Rundles, C., et al., "Zinc deficiency, depressed thymic hormones and T-lymphocyte dysfunction in patients with hypogammaglobulinemia", Clin. Immunol. Immunopathol., 21: 387 (1981).
26. Good, R.A., et al., "Zinc and immunity", in Clinical, Biochemical, and Nutritional Aspects of Trace Elements, Prasad, A.S. Ed., Alan R. Liss, New York (1982).