When one makes a study of evolutionary medicine-type issues (that is, all chronic Western disease mediated by inflammation and diet and lifestyle so far removed from the life our bodies were designed for), the same nutrients keep popping up again and again. Fish oil is a good example. Yes, for heaven's sakes. I'm taking my fish oil. Shut up about it already.
When examining the small unexplored niche of nutritional evolutionary psychiatry, however, another trace mineral nutrient keeps bobbing to the top. This warrants a post, of course (or two, or three). Yup, no surprises here - I'm talking about zinc.
Let's start with the basics. This first bit of info comes from a rather abruptly titled "Zinc and depression. An update." from Poland in 2005. No cutesy titles in Poland! They get down to business. Good. I'm from Texas. I prefer cute yet vaguely threatening, myself (i.e. "Don't mess with Texas" as an anti-littering campaign - Also, driving out in the hill country, a large sign with scarecrow: "No trespassing. We don't call 911.") Gulp.
Zinc is a trace mineral (like magnesium, iodine, selenium, et al) that is essential for our continued life. Turns out that 300 or more enzymes in our bodies use zinc as a buddy to help them do their thing. DNA replication, protein synthesis, cell division - basic, mondo important, reliant on the presence of zinc. And guess what - the highest amount of zinc in our bodies is found in the brain - specifically in our hippocampus and cerebral cortex. Zinc deficiency can therefore lead to all sorts of unlovely consequences, such as ADHD, depression, alterations in behavior, learning, mental function, and seizures.
Turns out scientists of yore did all sorts of horrible tests on rats to figure out how zinc might be related to depression. Antidepressants seem to increase the ability of zinc to work as an anti-inflammatory agent in rat brains, zinc alone seems to be an antidepressant for rats, and the combination of zinc + small amounts of different classes of antidepressants (TCAs and SSRIs) enhanced the ability of the antidepressants to do their thing (helping the rats swim longer in hopeless situations, for example, or endure being held by their tails. Is reality TV really any different?).
Zinc therapy in rats also increases the amount of BDNF in rat hippocampi. Readers of the archives will note I am a big fan of BDNF in the hippocampus. And zinc reduced the fighting behavior of rats (and prisoners) too!
Yes, humans. Turns out Maes (my new hero - churned out a 62 page article on inflammation and depression this year, which I now have in my hot little hands!) discovered that zinc is low in the serum of humans with depression. Also, that low zinc seems to affect inflammation and immunity. Our T-cells (members of the immune system who hunt and kill infection) don't work well without zinc, and seem to release more inflammatory cytokines (IL-6 and IL-1) with low levels of zinc. Also, one of zinc's special actions is to inhibit the NMDA receptor in the brain. In suicide victims, there seems to be an alteration of zinc's ability to affect the NMDA receptor. (Turns out, BDNF + zinc helps calm down the NMDA receptor, leading to antidepressant effects.) Can zinc supplementation have antidepressant effects in humans? You may not be surprised at this point that the answer is yes (1).
There is more, much, much more to the story of zinc and psychopathology, but for now, let's end with good sources of zinc in our diets. Not surprisingly, the best sources of zinc are protein-rich meats, such as beef, pork, lamb, shellfish (especially oysters), chicken, turkey, etc. Pumpkin seeds are also a good non-meat source, and while grains have zinc, the absorption is strongly affected by the phytic acid in grains (2). Vitamin C, E, and B6 help you absorb zinc also. Seems that people with intestinal problems (celiac disease, inflammatory bowel), vegetarians, those with chronic kidney and liver diseases, alcoholics, and the elderly are most likely to suffer from zinc deficiency (3). Intake of more than 50mg a day (both from diet and from supplements) can lead to improper copper metabolism, altered iron function, reduction of HDL and reduced immune function.
More on zinc to come!
Showing posts with label hyperactivity. Show all posts
Showing posts with label hyperactivity. Show all posts
Thursday, July 22, 2010
Saturday, July 17, 2010
A Closer Look at Tartrazine
Tartrazine, also known as Yellow #5, is a coal-tar derivative azo dye found in a lot of processed food, including Kraft Macaroni and Cheese, Doritos, Mountain Dew, Peeps, and many soups, custards, mustards, baked goods, cotton candy, ice cream and tons and tons more. It's also in a million and one other products we may use on a daily basis - lotions, face soaps (including the one I used this morning), body soaps (including the one I used this morning!), cosmetics, shampoos, hand stamps - you name it! Despite this multimodal ingestion and cutaneous exposure, only a very small amount of the dye is used in each product, so total exposure might be around 1 teaspoon in a year (from wikipedia, so take that number with a grain of salt) (The CSPI site says around 12.75mg a day on average based on usage data - but probably more for kids and those who live on Mountain Dew). There's no reason, though, to freak out and empty out the pantry and medicine cabinet. Dose is important. But, as we well know, some of us can bathe in toxic substances and come out smelling like a rose, and others are sensitive to very small amounts.
The reason I'm looking at it more closely today is because if you hunt around the internet searching for possible creepy things about industrial food dyes, tartrazine has the worst reputation. And, indeed, it was one of the several dyes used in the Southampton Study I discussed earlier this week - and the whole study cocktail of dye and preservative did lead to increased hyperactivity in kids. Its use as a food additive is subject to a ban in the UK and voluntary bans in other European countries, like Norway. In fact, the Center for Science in the Public Interest in the US called for the FDA to ban Yellow Number 5 on June 30, 2010. (Here's a cute PDF from CSPI - Food Dyes, a Rainbow of Risk.)
But how might tartrazine cause problems? Well, some people (around 1/10,000, more or less) are definitely allergic to it. Hives, purpura, anaphylaxis, the real deal. This is why the FDA declared that it has to be on the labels of food if it is used - for people with hypersensitivity, and you can run afoul of the FDA if you include tartrazine in your product and don't label it (1). Not unusual - lots of natural and manmade chemicals cause allergic reactions in some people. It would be an unfortunate allergy to have, as yellow number 5 is in all sorts of things you wouldn't expect. Also, there seems to be a cross-reactivity in some people with asthma between tartrazine and aspirin - people with asthma caused by aspirin also seem to have asthma caused by tartrazine (2), and using desensitization techniques (gradual increasing exposure) to reduce aspirin sensitivity in one case study protected against the effects of tartrazine too. (3). Hmmm.
What about other actions of tartrazine? I couldn't find much. One study showed that application of small amounts of tartrazine caused contraction of intestinal muscle cells in guinea pigs, and the effect was blocked by atropine. That clues us in that tartrazine seems to be able to activate the parasympathetic nervous system, either directly or indirectly, via the muscarinic receptor (4). Now that is quite interesting, as the central nervous system has lots of muscarinic receptors of all types known (M1-M5). Various activating agents of these receptors can cause things such as confusion, convulsions, restlessness, and psychosis - in high enough doses. At lower doses they can sometimes do the opposite, and cholinesterase inhibitors (which increase the CNS activity of acetylcholine, a muscarinic activator) are used to treat dementia. We've taken several big leaps at this point, but it is theoretically possible that if tartrazine gets into the central nervous system, this muscarinic receptor activation might be a mechanism for some sort of psychiatric reaction (like increasing hyperactivity).
The most intriguing information comes from this study from 1990 about how tartrazine influences the zinc status of hyperactive children. Now I'm still trying to get my hands on the full text - institutional access website is being coy the last few days, and it seems this journal is only available online from 1995 on anyway. But the abstract is telling. 20 hyperactive boys and 20 "aged matched controls" were tested for zinc levels in their saliva, urine, 24 hour urine, scalp hair, fingernails, and blood. The hyperactive kids had decreased zinc everywhere but the saliva. Then 10 control kids and 10 hyperactive kids were given a tartrazine-containing drink. In the hyperactive kids, the blood levels of zinc went down and the urine levels of zinc went up, and their behavior got worse, suggesting that tartrazine caused them to pee out some much-needed zinc. It's a bit hard to tell from the abstract, but the way I read it, it looks like the control kids zinc levels didn't change, and neither did their behavior. So that might be the mechanism by which yellow number five influences hyperactivity in certain kids. Ironically enough, Concerta, a formulation of Ritalin, has yellow number 5 as a colorant in the capsule!
The only other dirt I found on yellow number five is that it was implicated also in reducing the absorption or metabolism of vitamin B6, leading to carpal tunnel syndrome, of all things (at least according to Dr. Murray). (Here's the link between B6 deficiency and carpal tunnel, anyway). The rumor that the yellow number 5 in Mountain Dew causes your testicles to shrink? Well, that's not true.
My stance is - for most kids there is no need to make a big scene at a birthday party by grabbing the bag of rainbow candy out of your kid's hand. But on a day to day basis, processed food should be avoided in favor of whole, real food anyway. Doing that will reduce exposure to the rainbow soup of chemicals in processed food. Not to mention the mountains of fructose, trans fats, and genetically modified ingredients. Real food is a win/win. Weirded out by yellow number 5 in shampoos and soap? Check the labels if it bothers you. Or use baking soda and apple cider vinegar as cheap alternatives to shampoo and conditioner.
The reason I'm looking at it more closely today is because if you hunt around the internet searching for possible creepy things about industrial food dyes, tartrazine has the worst reputation. And, indeed, it was one of the several dyes used in the Southampton Study I discussed earlier this week - and the whole study cocktail of dye and preservative did lead to increased hyperactivity in kids. Its use as a food additive is subject to a ban in the UK and voluntary bans in other European countries, like Norway. In fact, the Center for Science in the Public Interest in the US called for the FDA to ban Yellow Number 5 on June 30, 2010. (Here's a cute PDF from CSPI - Food Dyes, a Rainbow of Risk.)
But how might tartrazine cause problems? Well, some people (around 1/10,000, more or less) are definitely allergic to it. Hives, purpura, anaphylaxis, the real deal. This is why the FDA declared that it has to be on the labels of food if it is used - for people with hypersensitivity, and you can run afoul of the FDA if you include tartrazine in your product and don't label it (1). Not unusual - lots of natural and manmade chemicals cause allergic reactions in some people. It would be an unfortunate allergy to have, as yellow number 5 is in all sorts of things you wouldn't expect. Also, there seems to be a cross-reactivity in some people with asthma between tartrazine and aspirin - people with asthma caused by aspirin also seem to have asthma caused by tartrazine (2), and using desensitization techniques (gradual increasing exposure) to reduce aspirin sensitivity in one case study protected against the effects of tartrazine too. (3). Hmmm.
What about other actions of tartrazine? I couldn't find much. One study showed that application of small amounts of tartrazine caused contraction of intestinal muscle cells in guinea pigs, and the effect was blocked by atropine. That clues us in that tartrazine seems to be able to activate the parasympathetic nervous system, either directly or indirectly, via the muscarinic receptor (4). Now that is quite interesting, as the central nervous system has lots of muscarinic receptors of all types known (M1-M5). Various activating agents of these receptors can cause things such as confusion, convulsions, restlessness, and psychosis - in high enough doses. At lower doses they can sometimes do the opposite, and cholinesterase inhibitors (which increase the CNS activity of acetylcholine, a muscarinic activator) are used to treat dementia. We've taken several big leaps at this point, but it is theoretically possible that if tartrazine gets into the central nervous system, this muscarinic receptor activation might be a mechanism for some sort of psychiatric reaction (like increasing hyperactivity).
The most intriguing information comes from this study from 1990 about how tartrazine influences the zinc status of hyperactive children. Now I'm still trying to get my hands on the full text - institutional access website is being coy the last few days, and it seems this journal is only available online from 1995 on anyway. But the abstract is telling. 20 hyperactive boys and 20 "aged matched controls" were tested for zinc levels in their saliva, urine, 24 hour urine, scalp hair, fingernails, and blood. The hyperactive kids had decreased zinc everywhere but the saliva. Then 10 control kids and 10 hyperactive kids were given a tartrazine-containing drink. In the hyperactive kids, the blood levels of zinc went down and the urine levels of zinc went up, and their behavior got worse, suggesting that tartrazine caused them to pee out some much-needed zinc. It's a bit hard to tell from the abstract, but the way I read it, it looks like the control kids zinc levels didn't change, and neither did their behavior. So that might be the mechanism by which yellow number five influences hyperactivity in certain kids. Ironically enough, Concerta, a formulation of Ritalin, has yellow number 5 as a colorant in the capsule!
The only other dirt I found on yellow number five is that it was implicated also in reducing the absorption or metabolism of vitamin B6, leading to carpal tunnel syndrome, of all things (at least according to Dr. Murray). (Here's the link between B6 deficiency and carpal tunnel, anyway). The rumor that the yellow number 5 in Mountain Dew causes your testicles to shrink? Well, that's not true.
My stance is - for most kids there is no need to make a big scene at a birthday party by grabbing the bag of rainbow candy out of your kid's hand. But on a day to day basis, processed food should be avoided in favor of whole, real food anyway. Doing that will reduce exposure to the rainbow soup of chemicals in processed food. Not to mention the mountains of fructose, trans fats, and genetically modified ingredients. Real food is a win/win. Weirded out by yellow number 5 in shampoos and soap? Check the labels if it bothers you. Or use baking soda and apple cider vinegar as cheap alternatives to shampoo and conditioner.
Thursday, July 15, 2010
Hyperactivity and Diet
Here's the title to a June 2009 article in the Harvard Mental Health Letter: "Diet and Attention Deficit Hyperactivity Disorder - Can some food additives or nutrients affect symptoms? The jury is still out."
Hmmm. That sounds very noncommittal. Let's start instead with the 2007 Southampton Study. Published in the Lancet, Britain's premier medical journal, this was a well-designed nutritional study! We're talking a randomized, placebo-controlled, crossover study. That's enough to make any biological scientist's heart go pitter patter. So what did the researchers do? They took 153 3 year-olds and 144 8/9 year-olds recruited from the community, and did a baseline measure of hyperactivity on the kids via a questionnaire filled out by teachers. All the kids were put on an additive and preservative free diet. At weeks 2, 4, and 6, half the kids were randomly/but in crossover fashion given a study juice drink containing either Mix A (with tartrazine (yellow #5), sodium benzoate, sunset yellow, carmoisine, ponceau 4R) or Mix B (sodium benzoate, sunset yellow, carmoisine, quinoline yellow, and allura red AC). Mix A was supposed to be equal to the additives and preservatives found in 2 bags of candy and was similar to a mix in previous studies, and Mix B to 4 bags of candy - meant to be a representation of the average amount of additives a kid on a normal diet might receive. The other half of the kids got a placebo drink that was the same color and flavor as the test drinks, but had no artificial colors or preservatives (I'm sure they managed it somehow). On weeks 3 and 5, everyone got a placebo (these were "washout weeks."
Then the researchers asked parents and teachers to assess the children's behavior using standard clinical instruments, and also asked independent reviewers to observe the kids at school. The investigators found a significant increase in hyperactivity during the weeks the kids (both 3 year olds and 8/9 year olds) consumed the drinks containing the artificial colors. Some kids appeared to be more vulnerable to the effect than others, but the overall effect was a 10% increase in hyperactivity. It was similar to the results found by an earlier meta analysis, and, in summary, the effect of removing additives from the kids' diet is about 1/3 the effect of giving kids Ritalin to calm them down.
The analysis of the study came down to this - some kids are very sensitive to additives, and their behavior will be significantly impacted. With other kids, it won't matter much. The results of the study, however, were impressive enough that the UK and several other European countries banned the use of the studied food additives, so Skittles sold in the UK have no sunset yellow or tartrazine, though as far as I know, Skittles in the US have the same old recipe of hyperactive family fun. Sodium benzoate was not banned.
So why is the Harvard Mental Health Letter so noncommittal? Well, they cite a well known study of 35 mother-son pairs where the mothers believed the boys, ages 5 to 7, were sugar sensitive. The researchers told the Moms that the boys would be randomly assigned to a dose of high sugar or a dose of aspartame. In reality, all the boys received aspartame. The mothers who thought their sons got sugar reported their child's behavior to be significantly more hyperactive afterward. "The researchers concluded that parental expectation may color perception when it comes to food related behaviors." Really? Well, doesn't a double-blind prospective cross-over design with independent examiners CONTROL for that sort of thing in the Southampton Study? I would think so.
The medical letter goes on to talk about Omega 6 to Omega 3 fatty acids (they recommended kids consume 12 ounces of low mercury shellfish or fish a week) and micronutrients (deficiencies in zinc, iron, magnesium, and vitamin B6 have been documented in children with ADHD, but there is no evidence that supplementation is helpful, and megadoses, which can be toxic, should be avoided). Eventually, they recommend "a healthful diet" for kids and minimizing processed and fast food. Well, I can get behind that. And, frankly, I don't recommend a steady diet of skittles to anyone, though it would be nice to have the option (as the European moms do) of having candy without the crappy additives. Since hyperactivity affects 10% of children (1), what they eat can have a large effect, overall, on kids and parents alike.
Hmmm. That sounds very noncommittal. Let's start instead with the 2007 Southampton Study. Published in the Lancet, Britain's premier medical journal, this was a well-designed nutritional study! We're talking a randomized, placebo-controlled, crossover study. That's enough to make any biological scientist's heart go pitter patter. So what did the researchers do? They took 153 3 year-olds and 144 8/9 year-olds recruited from the community, and did a baseline measure of hyperactivity on the kids via a questionnaire filled out by teachers. All the kids were put on an additive and preservative free diet. At weeks 2, 4, and 6, half the kids were randomly/but in crossover fashion given a study juice drink containing either Mix A (with tartrazine (yellow #5), sodium benzoate, sunset yellow, carmoisine, ponceau 4R) or Mix B (sodium benzoate, sunset yellow, carmoisine, quinoline yellow, and allura red AC). Mix A was supposed to be equal to the additives and preservatives found in 2 bags of candy and was similar to a mix in previous studies, and Mix B to 4 bags of candy - meant to be a representation of the average amount of additives a kid on a normal diet might receive. The other half of the kids got a placebo drink that was the same color and flavor as the test drinks, but had no artificial colors or preservatives (I'm sure they managed it somehow). On weeks 3 and 5, everyone got a placebo (these were "washout weeks."
Then the researchers asked parents and teachers to assess the children's behavior using standard clinical instruments, and also asked independent reviewers to observe the kids at school. The investigators found a significant increase in hyperactivity during the weeks the kids (both 3 year olds and 8/9 year olds) consumed the drinks containing the artificial colors. Some kids appeared to be more vulnerable to the effect than others, but the overall effect was a 10% increase in hyperactivity. It was similar to the results found by an earlier meta analysis, and, in summary, the effect of removing additives from the kids' diet is about 1/3 the effect of giving kids Ritalin to calm them down.
The analysis of the study came down to this - some kids are very sensitive to additives, and their behavior will be significantly impacted. With other kids, it won't matter much. The results of the study, however, were impressive enough that the UK and several other European countries banned the use of the studied food additives, so Skittles sold in the UK have no sunset yellow or tartrazine, though as far as I know, Skittles in the US have the same old recipe of hyperactive family fun. Sodium benzoate was not banned.
So why is the Harvard Mental Health Letter so noncommittal? Well, they cite a well known study of 35 mother-son pairs where the mothers believed the boys, ages 5 to 7, were sugar sensitive. The researchers told the Moms that the boys would be randomly assigned to a dose of high sugar or a dose of aspartame. In reality, all the boys received aspartame. The mothers who thought their sons got sugar reported their child's behavior to be significantly more hyperactive afterward. "The researchers concluded that parental expectation may color perception when it comes to food related behaviors." Really? Well, doesn't a double-blind prospective cross-over design with independent examiners CONTROL for that sort of thing in the Southampton Study? I would think so.
The medical letter goes on to talk about Omega 6 to Omega 3 fatty acids (they recommended kids consume 12 ounces of low mercury shellfish or fish a week) and micronutrients (deficiencies in zinc, iron, magnesium, and vitamin B6 have been documented in children with ADHD, but there is no evidence that supplementation is helpful, and megadoses, which can be toxic, should be avoided). Eventually, they recommend "a healthful diet" for kids and minimizing processed and fast food. Well, I can get behind that. And, frankly, I don't recommend a steady diet of skittles to anyone, though it would be nice to have the option (as the European moms do) of having candy without the crappy additives. Since hyperactivity affects 10% of children (1), what they eat can have a large effect, overall, on kids and parents alike.
Subscribe to:
Comments (Atom)