Ronald Steriti, ND, PhD
This week's research review focuses on a recent LA Times article (see attached) on the dangers of zinc overdose that can occur when using some over-the-counter products, such as denture cream (for example, Poligrip or Fixodent), which contains 17 to 34 milligrams per gram. That means that some people were exposed to as much as 330 milligrams of zinc a day.
Below are some relevant articles, including one on glutathione.
Lim, J. H., G. E. Davis, et al. (2009). "Zicam-induced damage to mouse and human nasal tissue." PLoS One 4(10): e7647.
Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc), a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.
(2009). "Over-the-counter medications: Zicam nasal products may cause loss of sense of smell." Child Health Alert 27: 3.
Flinn, J. M., D. Hunter, et al. (2005). "Enhanced zinc consumption causes memory deficits and increased brain levels of zinc." Physiol Behav 83(5): 793-803.
Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (microSXRF) confirmed that brain zinc levels were increased by adding ZnCO3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function.
Linkous, D. H., P. A. Adlard, et al. (2009). "The Effects of Enhanced Zinc on Spatial Memory and Plaque Formation in Transgenic Mice." J Alzheimers Dis.
There is considerable evidence suggesting that metals play a central role in the pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals may both precipitate and potentiate an Alzheimer's disease phenotype. Despite this, there remain few studies that have examined the behavioral consequences of elevated dietary metals in wild type and Alzheimer's disease animals. To further investigate this in the current study, two separate transgenic models of AD (Tg2576 and TgCRND8), together with wild type littermates were administered 10 ppm (0.153 mM) Zn. Tg2576 animals were maintained on a zinc-enriched diet both pre- and postnatally until 11 months of age, while TgCRND8 animals were treated for five months following weaning. Behavioral testing, consisting of "Atlantis" and "moving" platform versions of the Morris water maze, were conducted at the end of the study, and tissues were collected for immunohistochemical analysis of amyloid-beta burden. Our data demonstrate that the provision of a zinc-enriched diet potentiated Alzheimer-like spatial memory impairments in the transgenic animals and was associated with reduced hippocampal amyloid-beta plaque deposits. Zinc-related behavioral deficits were also demonstrated in wild type mice, which were sometimes as great as those present in the transgenic animals. However, zinc-related cognitive impairments in transgenic mice were greater than the summation of zinc effects in the wild type mice and the transgene effects.
Walther, U. I., S. C. Walther, et al. (2008). "Enhancing glutathione synthesis can decrease zinc-mediated toxicity." Biol Trace Elem Res 122(3): 216-28.
Zinc toxicity has been linked to cellular glutathione: A decrease in glutathione is followed by an increase in zinc-mediated toxicity. The question arises whether an increase in glutathione synthesis might decrease zinc-mediated cytotoxicity. We incubated five cell lines (hepatoma and lung-derived) with zinc chloride and 2 mmol/l N-acetyl-L-cysteine (NAC) to support glutathione synthesis. In all but one hepatic cell line, the glutathione content was increased by NAC as compared to the D-enantiomere NADC, whereas NADC did not increase GSH content as compared to not treated controls. In both alveolar epithelial cell lines, an increase in zinc tolerance was observed due to NAC as compared to NADC. In native fibroblast-like and the hepatoma cell lines, no changes in zinc tolerance were found due to NAC. In the fibroblast-like cells, zinc tolerance was increased due to NAC only after cellular glutathione had been previously decreased (by lowered cysteine concentrations in the medium). Enhancing glutathione synthesis can antagonize zinc-mediated toxicity in the alveolar epithelial cell lines, whereas some other characteristics than glutathione synthesis might be more important in other cell types. Furthermore, NAC acted as a GSH precursor only at cysteine medium concentrations of 10 micromol/l or below and therefore might be described as a poor cysteine repletor for glutathione synthesis.
It took a little while to locate this article on zinc, which states that the form of zinc is important when used for the common cold - zinc gluconate or acetate lozenges.
A review article concluded that zinc had no therapeutic effect on the common cold. (Caruso, Prober et al. 2007)
Eby disputes this conclusion. He re-analyzed the data based on the dose of ionic zinc, the active form, and found statistically significant correlations between total daily dose of ionic zinc and reduction in median duration and mean duration of colds but not between total zinc received and mean duration of colds. This report showed that nearly all single-ligand zinc gluconate and zinc acetate lozenges succeeded in reducing the duration of colds and nearly all multiligand zinc lozenges failed in the reducing the duration of colds. (Eby 2008)
I've attached the Eby article (you have to skip to page 10) along with a recent article from Alternative Medicine Review.
Eby, G. A. (2008). "Therapeutic effectiveness of ionic zinc for common colds." Clin Infect Dis 46(3): 483-4.
Caruso, T. J., C. G. Prober, et al. (2007). "Treatment of naturally acquired common colds with zinc: a structured review." Clin Infect Dis 45(5): 569-74.
Roxas, M. and J. Jurenka (2007). "Colds and influenza: a review of diagnosis and conventional, botanical, and nutritional considerations." Altern Med Rev 12(1): 25-48.
By Emily Sohn
December 21, 2009
With at least two flus and plenty of colds, coughs and sore throats circulating this season, some Americans are turning to zinc to ward off viruses.
Lozenges, supplements and nasal sprays that contain the mineral claim to boost immunity, and there is some evidence that they might do so. In an effort to stay well, though, we might be making ourselves sick. Consistently taking excessive amounts of zinc, according to early evidence, could lead to learning and memory problems, nerve damage, urinary tract problems and other negative effects.
With supplements that provide many times the recommended daily intake, cold medicines that are loaded with zinc and an abundance of fortified foods -- on top of the zinc already in a healthy diet -- overdoing it might be easier than you think.
"Everyone pays attention to zinc deficiency, and we need to get the story out that that's there, but that doesn't mean we need to gobble up boatloads of this stuff," says Jane Flinn, a psychologist at George Mason University in Fairfax, Va., who specializes in the effects of metals on learning, memory and Alzheimer's disease. Working with mice, she was one of the first to spot zinc's potential dangers. "You can fortify too much."
So far, side effects from zinc appear to be largely limited to people who have sprayed it deep into their sinus passages, slathered lots of denture cream on their gums, taken huge doses of supplements for medical conditions or drunk water from private wells that use galvanized pipes or tanks, especially in high-zinc areas. But because many Americans think that if a little of something is good then a whole lot might be better, some doctors and nutrition experts are raising red flags now.
For most people, zinc is a good thing, but troubles come with both too little and too much of it, says Ruth Frechman, a registered dietitian in Burbank and a spokeswoman for the American Dietetic Assn. Some Americans may need to work harder to get enough zinc, she says, including people older than 60, vegetarians, alcoholics, pregnant women, exclusively breastfed babies between 7 and 12 months old, and people with certain diseases. People who pound supplements, on the other hand, are at danger of getting too much.
Zinc keeps bodies humming in all sorts of ways. It's involved in DNA repair, wound healing and the sense of smell. It allows about 100 enzymes to do their jobs.
Zinc deficiency is a major public health crisis among poor people in developing countries. Not getting enough of it can damage memory, eyesight, taste buds and the immune system. Among other symptoms, zinc deficiency can cause growth retardation and diarrhea, especially among children. Zinc supplementation in these places can go a long way toward saving lives.
In North America, though, scientists are starting to recognize that getting too much zinc might be a bigger problem. The recommended daily intake is 11 milligrams for men and 8 milligrams for women. In a nation of plenty, it's easy to exceed those amounts.
There are more than 75 milligrams of zinc in six oysters, nearly 9 milligrams in a 3-ounce serving of cooked beef shanks, more than 3 milligrams in a cup of baked beans, 15 milligrams in a cup of some fortified cereals and 15 milligrams in many multivitamins.
All that zinc adds up. Studies show that consuming at least 50 milligrams a day for a few months could lead to copper deficiency, which can cause anemia, bone loss, nerve damage and other problems. Taking in 80 or 100 milligrams or more for months or even years can cause bigger problems, some irreversible. A typical, over-the-counter zinc supplement contains 50 milligrams. There are 13 milligrams in one popular brand of zinc lozenges.
In one of the first papers pointing to zinc's potential dangers, Flinn and colleagues fed zinc-enhanced water to pregnant rats and to their babies after birth. The water contained hundreds of times as much zinc as normal tap water. Three months later, it took longer for the zinc-fortified rats to learn how to find a submerged platform in an underwater maze, compared with rats that weren't full of zinc.
After a six-month break from testing, the same rats (who had continued to drink zinc-enhanced water) were much worse at remembering where the platform was. They grew more anxious during the test, the researchers reported in 2005 in the journal Physiology & Behavior. The study also showed increased levels of zinc in the rodents' brains, further suggesting that zinc was causing cognitive harm.
And in November, in the Journal of Alzheimer's Disease, Flinn and colleagues reported Alzheimer's-like memory problems in mice that were fed a zinc-enriched diet.
Zinc, copper and iron are all found in the plaque that builds up in brains of Alzheimer's patients. And while researchers try to figure out what that means, data suggest that removing zinc from the brain slows mental decline, says Imre Lengyel of University College London's Institute of Ophthalmology who has published studies on links between zinc and macular degeneration.
Some companies, Lengyel says, are even experimenting with drugs that remove zinc from areas such as the brain, where it may be causing damage, and redistribute it to other cells that are deficient.
"It sounds a little like science fiction, but it has some scientific support," Lengyel says.
Zinc raised other alarms last year, when researchers began to notice weakness, balance and memory issues and other neurological trouble in some patients. Sleuthing revealed the only common link: All of the patients used large amounts of denture cream enhanced with zinc.
Denture cream is meant to be used in small amounts, says Jaya Trivedi, a neurologist at the University of Texas Southwest Medical Center in Dallas. But people with poorly fitting dentures may end up using much more of it to keep their dentures in place. Trivedi and colleagues published their analysis of four denture-wearing, zinc-overloaded patients in the journal Neurology in 2008.
A tube of denture cream should last a month or more, Trivedi says. The patients in her study, however, had been using up to two tubes a week of Poligrip or Fixodent creams for many months or even years.
Zinc concentrations ranged from 17 to 34 milligrams per gram of denture cream, testing showed. That means that some people were exposed to as much as 330 milligrams of zinc a day, Trivedi says, though it's still not clear how much of that zinc actually got into their bloodstream. In some cases, nerve damage was permanent. Packages of Super Poligrip now include inserts telling people to talk to their doctors if also taking zinc supplements and to use the products as directed.
"We don't want everyone out there using denture cream to get scared. That's not our message," Trivedi says. Instead, she says, denture wearers should see a dentist if their dentures fit poorly, if they use a lot of cream or if they start to experience neurological problems.
Link to cancer
The brain isn't the only region of concern with zinc. The prostate contains some of the highest levels of zinc in the human body, and some evidence suggests a link between zinc and prostate cancer.
Zinc also builds up in the back of the retina in people with macular degeneration, Lengyel found in a 2007 study published in the journal Experimental Eye Research. And that may be causing unexpected problems.
Zinc is essential for proper eye function, and in an attempt to defy macular degeneration -- the major cause of blindness in elderly people in the Western world -- doctors have often prescribed supplements that contain 80 milligrams of zinc. In a small percentage of these cases, studies show, the metal helps slow the progression of blindness by a year or two.
More recently, however, Lengyel has found that people who take these extra-large supplements for years are 50% more likely to end up in the hospital with urinary tract problems. In a group of more than 3,500 people, about 11% had urinary complications, compared with about 7.5% of people who took zinc-free supplements.
"I don't think we have seen the real nasty path or potential of long-term supplementation," Lengyel says. "I don't think that's surprising. Any chemical you take in large excess is going to cause problems, even the good ones."
Researchers recommend avoiding nasal sprays containing zinc, as well. An October study in the journal PLoS One found that the Zicam brand of homeopathic zinc-enriched nasal spray caused long-term damage to the sense of smell in mice and signs of nasal nerve damage in people.
When it comes to supplements, sucking on zinc lozenges as soon as you get a cold may help and probably won't hurt, experts say, as long as you don't suck on them all day every day for the entire flu season. A week should be fine.
Some promising research is also starting to suggest that a tiny bit of copper supplementation can help override the dangers of getting too much zinc. In the meantime, experts suggest staying well the old-fashioned way: Eat a healthy diet, and stop staying up so late.