View Full Version : biomarkers and iron in the brain


datajunkie
06-18-14, 10:01 AM
http://www.medicalnewstoday.com/articles/278362.php?tw

so do AD/HD'ers use more iron in the brain? don't take it up as well? how are meds altering the levels of iron in the brain?

mildadhd
06-18-14, 08:38 PM
... so do AD/HD'ers use more iron in the brain? don't take it up as well?...

Seems like some infants are born with lower iron levels?

Iron plays an important role in the development of organ systems, especially the brain. Well-known risk factors for poor iron status in infants are maternal iron deficiency, maternal diabetes, smoking during pregnancy, preterm birth, low birthweight and multiple pregnancy

I wonder how many of the 63 infants in the article below have ADHD?


Results showed that the 63 babies whose mothers were in the stress group had significantly lower cord-blood ferritin concentrations than the 77 infants in the control group.

Mom's stress during pregnancy can affect baby's iron status (http://www.sciencedaily.com/releases/2012/04/120429085406.htm)


.?

datajunkie
06-18-14, 11:14 PM
The iron in the brain being low but not in the circulating blood could be due to various glitches. Uptake was mentioned, something preventing the iron from getting taken up into the cells as needed. Possibly a higher metabolic demand, might be an inefficiency causing more to be utilized and excreted.
In my years of breeding dogs, copper toxicity and zinc deficiency were subjects of discussion. Some breeds have more issues. They are genetic. The toxicity--holding too much copper found in a 'normal' diet could be an adaptation to a regional diet low in copper, the enzymes needed to excrete it are variants that are weaker than most breeds and the opposite with zinc, most of the breeds that need higher levels of zinc originated in areas where the diet had high levels of zinc. this could either be an adaptation to prevent zinc toxicity--either not absorbed well from the diet or some extra efficient metabolic pathway causing more to be excreted. Or it might not have been so much zinc in the diet that it was an active evolutionary selection but that the diet high in zinc covered up what would have been a weakness in other regions. So it wasn't selected against. Slightly different evolutionary pathways. But these are truly genetic, not effects during fetal development.

The stress factors in your article can affect cognition as well as other health factors. Smoking is a risk factor for ADD. But the low iron in the umbilical cord may not reflect low iron in the brain. A follow up on those infants might be useful.

mildadhd
06-18-14, 11:49 PM
The iron in the brain being low but not in the circulating blood could be due to various glitches. Uptake was mentioned, something preventing the iron from getting taken up into the cells as needed. Possibly a higher metabolic demand, might be an inefficiency causing more to be utilized and excreted.
In my years of breeding dogs, copper toxicity and zinc deficiency were subjects of discussion. Some breeds have more issues. They are genetic. The toxicity--holding too much copper found in a 'normal' diet could be an adaptation to a regional diet low in copper, the enzymes needed to excrete it are variants that are weaker than most breeds and the opposite with zinc, most of the breeds that need higher levels of zinc originated in areas where the diet had high levels of zinc. this could either be an adaptation to prevent zinc toxicity--either not absorbed well from the diet or some extra efficient metabolic pathway causing more to be excreted. Or it might not have been so much zinc in the diet that it was an active evolutionary selection but that the diet high in zinc covered up what would have been a weakness in other regions. So it wasn't selected against. Slightly different evolutionary pathways. But these are truly genetic, not effects during fetal development.

The stress factors in your article can affect cognition as well as other health factors. Smoking is a risk factor for ADD. But the low iron in the umbilical cord may not reflect low iron in the brain. A follow up on those infants might be useful.

All humans can have ADHD, so I don't think ADHD genetics are limited to a certain group of humans.

Gene variants can be turned on and off by the environment.

So to say something is genetic doesn't rule out environmental factors, that may determine what gene variants are expressed.

It would be interesting to follow up on the infants in the article.

Guessing, I don't think all 63 infants would have ADHD, although I am wondering if the prenatal exposure to some types of distress, would make expression of gene variants related to ADHD or/and other psychological health issues more likely.


P

datajunkie
06-19-14, 12:17 AM
All humans can have ADHD, so I don't think ADHD genetics are limited to a certain group of humans.
<< I don't understand this sentence. what do you mean genetics limited to a certain group of people? There are genes that make those carrying them more likely to have ADHD but not even identical twins have 100% risk if 1 twin is ADHD. I've read 60-80% chance of both twins having ADHD. >>

Gene variants can be turned on and off by the environment. << not always. there are some genes for things like coat color in dogs that are straight dominant/recessive. In my breed, Dobermans, black is dominant over red coats. A double black gene dog can not produce offspring with red coats even if bred to a red dog. that red dog is recessive, has 2 red genes. 2 red dogs can not produce black dogs. a black dog carrying a red gene bred to a red dog will have about equal numbers of red and black pups. But the color variation in the red dogs as well as the color of the rust markings on the black dogs will have some changes depending on diet and such. The lightening gene that gives blues and fawns has an oddity that goes with it in that many but not all of these dogs lose hair and may be totally bald. The Z factor 'white' dobermans usually have some traces of color but blue eyes, pink skin and very prone to skin cancer as well as usually having bad health and weak temperament from too much inbreeding--that Z factor gene should be banned and good breeders won't breed to such dogs. The breeders who do churn them out breed too closely and produce crappers not worth feeding. Some genes have variants affected by environment but some are pretty straightforward.

So to say something is genetic doesn't rule out environmental factors, that may determine what gene variants are expressed. << Unless someone has a copy number variation with 3 or more copies of genes instead of the usual 2 copies, there isn't that much variation to choose from, 2 genes, both may be expressed to some degree, both inhibited or one more than the other. and at different times depending on what other genes regulate a gene down the chain of responses. BUT, in many cases there are limits in how far a gene can be turned up. Enzymes often fit into this. In dogs, one gene variant that metabolizes some agricultural chemicals--can't find the paper at the moment, think it is a class of pesticides, is 60 times more productive than another variant. A dog carrying 2 copies of that gene might be able to drink a dose that would kill 60 other dogs carrying 2 copies of the weak variant. There is no way to make those weak variants produce more than their upper limit. There may be ways to reduce the expression of the powerful variant. It wastes metabolic energy to produce more of an enzyme than needed.
In answer to your last question, watch this video. https://www.youtube.com/watch?v=8Af8T9L0HiA I highly suggest watching the whole series from the beginning. And check youtube for any by Sapolsky, he has a video on depression plus some other more in depth lecture series. He's funny and gets the information across to the lay person in understandable forms without dumbing down.

mildadhd
06-29-14, 09:48 AM
When children are deprived of iron at any point during the last trimester of pregnancy or the first six months of life—a critical period of brain development—they suffer brain damage at least through early adulthood, and possibly beyond. In particular, their motor function can be impaired as well as their ability to focus.

http://www.hhd.psu.edu/news/2011/2_6_11_ritalin.html


I am wondering if "early iron deficiency damage", could be a possible biomarker, for possible later life substance abuse problems, as well as ADHD and other emotional health issues?



Abstract
Increases in basal ganglia iron are well documented for neurodegenerative diseases but have not been associated with methamphetamine (METH). In this study, vervet monkeys that received two doses of METH (2 mg/kg, intramuscularly, 6 h apart) showed at 1 month, iron increases in substantia nigra pars reticulata and globus pallidus, with concurrent increases of ferritin-immunoreactivity and decreases of tyrosine hydroxylase-immunoreactivity in substantia nigra. At 1.5 years, substantia nigra tyrosine hydroxylase-immunoreactivity had recovered while iron and ferritin-immunoreactivity increases persisted. Globus pallidus and substantia nigra iron levels of the adult METH-exposed animals (age 5-9 years) were now comparable with those of drug-naive, aged animals (19-22 years), suggesting an aging-related condition that might render those regions more vulnerable to oxidative stress.

http://www.ncbi.nlm.nih.gov/pubmed/17921879/

datajunkie
06-29-14, 11:41 AM
That seems quite possible. Iodine deficiency may be similar. http://www.ncbi.nlm.nih.gov/pubmed/15579758
I found reading this report disgusting. And valid reason that experimenting first on lab rats can prevent lifelong human burden. That the pregnant women in an area known to be low in iodine and who were shown to have low thyroid function were not supplemented with either iodine/iodide or thyroid medication in order for the test to be valid may well have doomed those children to lifelong issues. And being hypothyroid didn't do their mothers any good either. This article was from 2004 and indicated the pregnancies were 10 years earlier. I don't know if such a revolting experiment would be permitted now.
On the flip side, toxicity from lead in gestation or childhood is linked with violent crime rates. Similar exposure to some agricultural chemicals is linked to several health, behavioral and cognitive issues. I don't know if I can easily find it, might have transferred it to an external hard drive but I was sent a PDF file written by a researcher for the EPA. Checking ground water levels of 3 chemicals, a fertilizer, pesticide and herbicide, did show that EPA accepted safe levels were indeed not associated with any health issues--individually. If only one was present, not a big deal if in drinking water, bathing water or irrigation on food that was eaten. However the 3 together had a surge in multiple problems. The 'control' on this if I remember correctly was a very similar genetic and cultural population across the border in Mexico. The population in the lowlands practicing US style use ag chemicals showed the same health issues as the US population but those in the mountains not using the chemicals and not showing a body load via blood testing, did not have any increase in these issues.
Deficiencies and toxicities, especially during gestation and growth, and exposure to many other chemicals we can't avoid now can cause a lot of damage. check a website for 'our stolen future'. Scary stuff. I'm less worried about the world being poisoned by nuclear bombs or power plant leaks than multiple forms of chemical poisoning. Deficiencies seem easier to detect and correct than the toxin exposure.

ginniebean
06-29-14, 12:42 PM
I read this article awhile ago. It would be nice to have an actual bio marker so people could get help that need it and we wouldn't be reliant on reporting which can result in false positives and false negatives.

mildadhd
06-29-14, 04:06 PM
Many biological substances have more than one "job", partially depending on period of development.

The different roles of brain iron, especially during early critical periods of brain development, when some brain areas are developing for the very first time, seem important to recognize.

Here is a great link that includes lots of topics for discussion, including, iron, dopamine, animal and human studies, etc.


Why Worry About Iron Deficiency?

2 billion people world-wide are iron deficient (WHO)
– 30-50% of pregnant women

Every cell/organ system needs iron for proper development and subsequent function

Iron deficiency anemia is associated with clinical symptoms

– Due to tissue level ID

– Symptoms occur prior to anemia because iron is prioritized to red cells before the brain when iron supply does not meet iron demand (Georgieff et al, 1992; Petry et al, 1992)

• ANEMIA IS A POOR SCREEN FOR RISK OF BRAIN ID

Main reason to worry is the effect on the developing brain
– Cognitive and motor effects
– Some temporary (while ID), others long-term (after iron repletion)...



...Summary

• Iron plays a critical role in early neurodevelopment

• Multi-layer investigations demonstrate that the behavioral deficits are due specifically to the lack of iron

• Early iron deficiency without anemia affects brain function

• ID brain/behavior alterations persist into adulthood

• Early detection of at risk infants is crucial for brain health

• Need new tools to detect pre-anemic iron deficiency


The Specific Role of Iron in Early Brain Development (http://www.mchip.net/sites/default/files/mchipfiles/The%20Specific%20Role%20of%20Iron%20in%20Early%20B rain%20Development_Georgieff.pdf)




P

datajunkie
06-29-14, 08:53 PM
Many nutrients need cofactors to be utilized properly. And the form of the nutrient can make a big difference in how bioavailable it is. Then add in the enzymes needed for things such as uptake, transport and excretion and it gets more complicated.
Calcium, magnesium and phosphorous all can cause the others to be excreted. ie too much phosphorous from a high animal protein diet may cause calcium and magnesium to be low. Oxalates and phytates in plant foods can lock out some of nutrients. Tea, as in green/black tea can cause iron to be excreted. In areas of the south where 'sweet tea' is popular, it can cause some degree of anemia.
Eating plant foods grown on nutrient rich soil, with a healthy microbe system to help the plants take up the nutrients, animal foods that were fed plant foods raised this way, adding in some sea foods--both fish/shellfish from the least polluted seas--and perhaps some seaweed from the same areas and a wide variety of these foods can give us much of what we need in forms our bodies can use if our digestion is good.
I can't eat nightshades very often. Potatoes, tomatoes, peppers, eggplant, as they are high in salicylates--aspirin related compounds, that a few percent of the population can't metabolize and excrete well. We lack the enzymes to do so. Much like lactose intolerance. This may be a genetic adaptation to long ago native diets low in these plant foods to help conserve them as they are useful. Eating too many potatoes in particular for me makes my joints ache the next day and I may be spacier than usual. If I eat them too often my gut starts to complain also.
Nutrition is biochemistry and more complex than I wish it was.

mildadhd
06-29-14, 10:48 PM
Here is another interesting/helpful link. (see link in full below)

The Timing of Integrated Early
Interventions: Nutrition, Stress and
Environmental Enrichment

Early Environment and Brain Development:
General Principles

Positive or negative effects on brain development

Based on…
Timing, Dose & Duration of Exposure
Kretchmer, Beard, Carlson
(1996)


“Environment” in our context:

1) Nutrition

2) Stress

3) Nurturing events

4) Combinations of 1-3


Environment->Brain->Behavior Relationships:
“Timing is Key”

• Brain is not a homogeneous organ

• Different brain regions have different developmental
trajectories

• Vulnerability of a brain region to environmental stimuli is
based on
– Timing of deficits/enrichment programs during the lifespan
– Brain region requirement for a nutrient, vulnerability to stress, and receptivity to enrichment at that time...






...Integrated Conclusions

• Early environment (prenatal to 3-5 years) profoundly affects developing primary brain structures necessary for:
– Fundamental brain functions
• Learning and memory, speed of processing, emotional reward
– Neural scaffolding for later developing complex circuits
• Higher cognitive functions

• Early events confer a lifetime of risk through epigenetic modification of critical genes

• The early years are not the sole sensitive time period,
– But the task is harder in later years

• Follow-up/follow-on interventions are crucial for children with multiple cumulative high risk events

• Integrated interventions are essential because neural, nutritional/metabolic, physiological and behavioral biology form a linked multi-dimensional system


The Timing of Integrated Early Interventions: Nutrition, Stress and Environmental Enrichment (http://www.iom.edu/~/media/Files/Activity%20Files/Children/iYCG/Cost-of-Inaction-Presentations/Georgieff.pdf)




P

datajunkie
06-30-14, 09:00 AM
Thanks P,
I will check out the charts. I was also being a bit facetious. Nutrition is something I've been taking seriously for over 35 years when I started bodybuilding and was one of the first women in a hard core spit sweat and swear gym and did a best lift of 347# deadlift at the age of 24. And what was considered 'true' at that time by most nutritional standards as a 'good' diet has changed so much since then.
I've also been feeding dogs for almost 30 years for breeding. From pre-pregnancy diet, through gestation, whelping, nursing, puppyhood, adolescence, seasonal demands, stress, and into caring for elderly dogs, a lot has changed in canine nutrition also. Some breeds are prone to copper toxicosis--rather like hemachromotosis in humans, they can't clear copper properly so need low copper diets. Other breeds need more zinc, they appear to either not absorb it well or excrete it too quickly. Possibly regional adaptations to low copper in the food--hang on to a rare nutrient! or high zinc and get the stuff out before it kills us!
But what I 'knew' 35 years ago is quite different from what I 'know' now and I expect that to frequently as more data comes in. My sweetheart has atrial fibrillation, and the swing from truly top research in how much fish oil is best for risk of fatality reduction literally flipflopped in less than 2 weeks.