5-Hydroxytryptophan (5-HTP): a clinically-effective serotonin precursor.

Altern Med Rev. 1998; 3(4):271-80

Birdsall TC 5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.

Glutamate "Blockers?"

Article that asks what things might be taken to block excess glutamates

Mike: Here's a practical question that's actually been burning in my head for about eight years: Is there anything that a person can take to block the absorption of MSG or glutamate as a defensive supplement?

Dr. Blaylock: Well, not necessarily to block it. You have other amino acids that can't compete for glutamic acid absorption. So that may be one way to help reduce the rate at which it would be absorbed.

Mike: Which aminos would those be?

Dr. Blaylock: Those would include leucine, isoleucine and lysine. They would compete for the same carrier system, so that would slow down absorption. There are a lot of things that act as glutamate blockers. You know, like silimarin, curcumin and ginkgo biloba. These things are known to directly block glutamate receptors and reduce excitotoxicity. Curcumin is very potent. Most of your flavonoids.

Magnesium is particularly important, because magnesium can block the MNDA glutamate type receptor. That's its natural function, so it significantly reduces toxicity. Vitamin E succinate is powerful at inhibiting excitotoxicity, as are all of your antioxidants. They found combinations of B vitamins also block excitotoxicity.

ADHD/Glutamates/Salicylates (from Australia)

My approach to ADD ADHD

Several factors involving cerebral Zinc (? and other metals), salicylates and glutamates.

For lists of these foods see http://www.zipworld.com.au/~ataraxy/Salic_03.txt

An overview is provided at http://209.1.158.41/b_nutrition/02solutions/03rx/food/food3.htm

What we know.

1] Tartrazine (food additive 102) can cause hyperactivity. Check out food colourings at http://ificinfo.health.org/brochure/foodcolr.htm

2] Tartrazine causes acute zinc loss in the urine (zincouria).

3] Those sensitive to 102 are usually sensitive to dietary (and prescribed) salicylates and glutamates.

4] Salicylates bind minerals such as copper (and probably zinc). Copper salicylates have been used in Rheumatoid Arthritis.

5] The compound Zinc-salicylate has similar biological appearance to glycine.

6] Glycine is an amino acid and inhibitory neurotransmitter.

7] Glutamate is an excitatory transmitter. MSG (additive 621) is a glutamate. Glutamates occur naturally in foods.

8] Salicylates require glycine for liver metabolism. Salicylglycine is the main excreted metabolite.

9] Salicylates accumulate in most fruits and some vegetables prior to ripening so as to defend themselves against being eaten. In the last 3 days of ripening, salicylate levels fall as antioxidants enter from the stem of the plant. For example, one large green apple will be converted to about 150mg of salicylate.

10] Green harvesting (picking fruit 7 days prior to ripening) will produce high salicylate, low antioxidant foods. Green harvesting is widely practiced in WA.

11] Because of generalized soil deficiencies, most of WA food sources are lower in zinc and selenium than ever before. Please note: The farmers know about this, the Agriculture Dept knows about this. The only group who do not know about this are the medical profession.

12] There are many foods that contain glutamates and salicylates. Apart from the obvious (additive 621 MSG), tomatoes, yeast extracts, tomato sauce, gravies, stock cubes, tomato paste, salami’s, meat pies, seasoned meats, grapes, plums, prunes, raisins, sultanas broccoli, mushrooms and spinach.

13] Hence, even "healthy eating" will result in low zinc, high salicylate condition. It will also put strain on glycine reserves.

Hypothesis.

1] Low or borderline low cerebral zinc levels will become further compromised by high salicylate diet.

2] Zinc-salicylate or Zinc-Tartrazine may competitively compete for glycine binding sites.

3] Glutamates are excitatory and so a combination of low zinc, high salicylate, high glutamate food such as pie and sauce or vegemite on toast could lead hyperactivity or another altered mental state.

4] If you combine the effect of Zinc soil deficiencies and high salicylate, high glutamate diet and no wonder WA has such a high rate of ADD/ADHD.

Diagnostic and treatment regimen.

1] Measure RBC zinc locally. I suggest Clinipath, but do not use their reference range as a guide. It is not useful for several reasons. If most of WA is deficient, then how can they provide a normal? Moreover, they have not (and cannot) sample randomly from the community at large to attain such values. In fact they use crossover testing. For example, if a patient's FBP is normal, they will assume that the RBC is also normal and include them in the melting pot of results. Now if the indication for the FBP was recurrent infections, then low zinc (despite a normal FBP) could well be the cause (not usually thought of by doctors although extremely well documented for about half a century now). If the physician is investigating hypoglycaemia, then zinc deficiency most often causes post-prandial hypoglycaemia, and glucose is usually normal (and hence put into the "normal" zincs) at the time of testing, because the doctor has not listened to the patient symptoms ("But doctor, I feel like my blood sugar is low 2-3 hours after a meal, not first thing in the morning"). The same is true for the investigation of joint pain, allergy, asthma, depression, infertility and hair loss. The FBP, LFT's and U&E's will be usually be normal and hence the zinc levels from these patients will bias the pool. If these are the type of samples being used for normals, then obviously they do not represent a normal population and make a mockery of any statistical approach to blood level testing.

2] If the level is less than 200 micromol/L, start zinc supplements. I use 1.5 to 2 mg/kg for the first month, usually in liquid form such as Metagenics "Zinc Drink" or "Orthoplex Zymin". Don't be squeamish, the toxic dose of zinc is 2000mg and most people will just vomit after 200mg.

3] Start a strict low salicylate diet. Beware, although most parents will flatly deny that they give their children anything unhealthy, most of these children will, in fact, be "addicted" to one of the high salicylate high glutamate foods (tomato sauce, peanut paste, muesli bars, gravies...), so be tough. Although unhappy at first, they'll thank you for it afterwards, I can promise you.

4] If you can, also measure RBC Magnesium, ferritin, Vitamin C, selenium and helicobacter serology.

5] Optimal levels, for RBC Mg is >2.30 mmol/L, ferritin is >30 micromol/L, Vitamin C is 50 micromol/L. Selenium is >1.0 micromol/L.

6] If you find helicobacter, treat it. It causes malabsorption years before it causes reflux, heartburn or ulcers. Iron deficiency precedes ulcers by at least 12 months!! Think of how many patients you've sent for endoscopies for investigation of iron deficiency who only had helicobacter with no ulcers and no occult faecal blood? How could this happen? Helicobacter causes parietal cell dysfunction. You need parietal cells to make the HCl to ionise Iron, Magnesium and Calcium. Your parietal cells need Vitamin B1, B6 and Zinc to make HCl. If you don't make acid then low acid food entering the duodenum will not stimulate the pancreas to make picolinic acid which is used to absorb zinc and chromium. Everyone knows this except the Gastroenterologists!

7] Just removing salicylates from the diet or just giving zinc will not always work. The other issues of low zinc low antioxidant intake and glutamates must be dealt with too.

Graphic- Magnesium Deficiency

Original Link

Bell Curve

Bell Curve Graphic

Potentially Toxic Doses of Vitamins/Minerals

Website Here

Optimal doses of vitamins/minerals for ADULTS

"Suggested Optimal Doses of Vitamins/Minerals for Adults." A table showing common symptoms of nutrient/mineral/vitamin deficiencies.

Magnesium

What does it do? Magnesium is needed for bone, protein, and fatty acid formation, making new cells, activating B vitamins, relaxing muscles, clotting blood, and forming ATP—the energy the body runs on. The secretion and action of insulin also require magnesium.

Magnesium also acts in a way related to calcium channel blocker drugs. This effect may be responsible for the fact that under certain circumstances, magnesium has been found to potentially improve vision in people with glaucoma.¹ Similarly, this action might account for magnesium’s ability to lower blood pressure.²

Since magnesium has so many different actions in the body, the exact reasons for some of its clinical effects are difficult to determine. For example, magnesium has reduced hyperactivity in children in preliminary research.³ Other research suggests that some children with attention deficit-hyperactivity disorder (ADHD) have lowered levels of magnesium. In a preliminary but controlled trial, 50 ADHD children with low magnesium (as determined by red blood cell, hair, and serum levels of magnesium) were given 200 mg of magnesium per day for six months.⁴ Compared with 25 other magnesium-deficient ADHD children, those given magnesium supplementation had a significant decrease in hyperactive behavior.

Magnesium levels have been reported to be low in those with chronic fatigue syndrome (CFS),⁵ while magnesium injections have been reported to improve symptoms.⁶ Oral magnesium supplementation has also improved symptoms in those people with CFS who had low magnesium levels in another report, although magnesium injections were sometimes necessary.⁷ However, other research reports no evidence of magnesium deficiency in people with CFS.^{8 9} The reason for this discrepancy remains unclear. People with CFS considering magnesium supplementation should have their magnesium status checked beforehand by a doctor. Only people with magnesium deficiency appear to benefit from this therapy.

People with diabetes tend to have lower magnesium levels compared with those who have normal glucose tolerance.¹⁰ Supplementation with magnesium overcomes this problem¹¹ and may help some diabetics improve glucose tolerance.

Magnesium may be beneficial for bladder problems in women, especially common disturbances in bladder control and the sense of “urgency.” A double-blind trial found that women who took 350 mg of magnesium hydroxide (providing 147 mg elemental magnesium) twice daily for four weeks, had better bladder control and fewer symptoms than women who took a placebo.¹²

Magnesium supplementation may reduce dehydration of red blood cells in sickle cell anemia patients. Administration of 540 mg per day of magnesium pidolate to sickle cell anemia patients was seen after six months, to reverse some of the characteristic red blood cell abnormalities and to dramatically reduce the number of painful days for these patients.¹³ This preliminary trial was not blinded, so placebo effect could not be ruled out. Magnesium pidolate is also an unusual form of magnesium. It is unknown whether other forms of magnesium would produce similar results.

Where is it found? Nuts and grains are good sources of magnesium. Beans, dark green vegetables, fish, and meat also contain significant amounts.

Cool Food site -- what vitamins are in my food?

Searchable Food listing Click on the food name, and you can see its nutritional values.

Excitotoxins in food (Glutamates, etc.)

Foods to Avoid, Foods to Enjoy

This is one of the newest pages that I have added to the Website. Much of this information has been on the site for years but has been buried deep in the sections that have required tedious scrolling to find them. Thankfully, a Website upgrade has changed all of that. So, here are the lists of foods rich in glutamate/aspartate and those that are lower in these two non-essential, neurostimulating amino acids that we are restricting in the excitotoxin-related conditions.

First of all, Here are a couple of great sites for looking up the nutritional profiles of food, including their glutamate and aspartate content. The newest and most comprehensive that I have found to date is http://www.foodcomp.dk/fcdb_alphlist.asp. Another is http://www.whfoods.com/foodstoc.php . In the latter, simply click on the food you are inquiring about, then scroll down toward the bottom of the page until you see the chart in the Nutritional Profile section. There is a click-on link after that chart (just above the References section) that reads "In Depth Nutritional Profile for (chosen food)" . Click on that link and then just scroll done to the aspartate and glutamate listings. Make note of the serving size at the top of the chart so that you'll be making an accurate comparison. You will quickly see the huge difference between the glutamate/aspartate content of healthy fruits/vegetables versus items such soy, wheat, barley, and the bean family (with the exception of green beans).

For example, recently my wife started eating peanuts and raisins as a late night television snack. Almost immediately, she started having very restless sleep and was complaining about soreness in her muscles and back. A quick trip to the chart showed very high levels of glutamate and asparate in peanuts.

I'm just glad that my canine patients don't eat peanut butter and jelly sandwiches and down it with a big glass of milk like our ADHD kids do. Let's see: wheat bread (with gliadorphins and plenty of glutamate and aspartate), peanut butter (LOTS more glutamate and asparate), jelly ("sugar gel"), and all of it washed down with cow milk (casomorphins and plenty of glutamate. Oh yeah. Don't forget the arachadonic acid for you pain sufferers).

Hmmmm..... It does all make sense, doesn't it?

Foods rich in glutamate and aspartate: 1) Grains: Wheat, barley, and oats are highest. Corn and rice are lower than the previous three but higher than potatoes. 2) Dairy Products: All Cheeses (cheddar, Swiss, Monterey Jack, Mozzarella, PARMESAN) are very high. Casein is very concentrated in cheese and is 20% glutamic acid by composition. 3) Beans: Soy, Pinto, lima, black, navy, and lentils 4) Seeds: Sunflower, pumpkin, etc. 5) Peanuts: Very high, as are cashews, pistachios, and almonds. I have more detailed charts on the site to show exact values for the various nuts. Everything in moderation applies when eating nuts of any kind. So, I do not recommend you reach for nuts when you are really hungry unless you can stop after a few. Nuts are very good for you..in moderation. For example, seven almonds a day gives you what you need . 6) Diet drinks: Primary source of aspartate (aspartame) 7) Prepared foods, soups: 70% of prepared foods and many soups have MSG 8) Meats: Note- All meats are naturally rich in glutamate and aspartate. Lamb (and eggs) are the lowest, while rabbit and turkey are the highest. However, I believe that the amount in a normal serving of meat should not be enough to cause problems. I think that it is all of the other "unnatural" sources when combined with the meats that are causing the problems. One of my newest concerns is the presence of glutamate in the flesh of grain-fed animals, especially chickens, turkeys, and cattle. This is a topic of discussion on the celiac forums and we are now believing that this is a real concern and could explain why some celiacs are not responding to elimination diets. Catfish are also grain fed. The fact is that 60-70% of the American Diet is wheat and dairy (with heavy emphasis on cheese). This combined with the amount of artificial sweeteners being consumed and the addition of SOY has led this country into an epidemic of pain syndromes, including fibromyalgia. Epilepsy is definitely on the rise in pets and the combination of wheat and soy in pet foods is playing a huge role. I am seeing first time epileptic dogs within three weeks of starting such diets. Food low in glutamate and asparate: 1) Fruits 2) Vegetables 3) Potatoes 4) Lamb and eggs are relatively low. 5) Tree nuts (e.g. pecans, walnuts, macadamias) NOTE: These are relatively low when compared to peanuts and cashews. I have more detailed charts on the site to show exact values. Pecans, for example, have half the amount of glutamate that peanuts have but that is still quite a bit. Again, everything in moderation applies when eating nuts of any kind. I do not recommend you reach for nuts when you are really hungry unless you can stop after a few. Nuts are very good for you..in moderation. 7 almonds a day gives you what you need .

Now, for the GOOD news:

On these dietary restrictions, I just want to make one thing very clear. We are restricting the level of glutamate and aspartate in the diet because the neurons of the brain (and their associated supportive cells called glial cells, or astrocytes) are diseased and cannot handle the high levels of this non-essential, neurostimulating amino acid in our typical diet. By eating what has become the Standard American Diet (S.A.D.), we are absolutely bombarding our brain with these “excitotoxins” in the form of grains, dairy, soy, and the rest.

But, it is the fact that the brain is unhealthy that explains why we are seeing the syndromes such as epilepsy, ADHD, insomnia, fibromyalgia, and various neurodegenerative diseases. I need to reemphasize this point for a number of reasons but mainly to establish why a person would develop one of these conditions and another not while eating the same foods. There must be something that distinguishes that person from the other…and there is…there always is. These things are covered elsewhere on the Website, but this might be a good time to check out my newest section, Viruses-Friend or Foe?

Here’s the point: When we are in the throws of one of the excitotoxin-related disorders, we need to reduce our consumption of the foods rich in these amino acids as much as possible. Doing so places a big Band-Aid on the situation and yields notable and often remarkable results in a short period of time. Dogs have stopped seizing in 24 hours. I felt noticeably better in four days. My fibromyalgia was improved in less than a week and gone in a month.

The phenomenal thing is that the long-term recovery also comes from the same diet. The principle reason this disease-producing cycle was set into motion to begin with was the damage effects of the “big 4” (gluten, casein, soy, and corn) on the intestinal villi and their ability to absorb vital nutrients. This combined with the showering of the body with exctotoxins, allergens, lectins, estrogens, and other substances from these same foods sets us up for the disease states that follow. Once the immune system starts to suffer from the same process, we are pretty much done.

The good news (yes, there is some good news) is that once we are off the “big 4” long enough, the process does reverse. Imagine the benefits of your body properly absorbing the calcium, iron, iodine, B complex, vitamin C, and trace minerals it so desperately needs. Imagine a brain, liver, and entire body that is getting what it needs to repair and thrive and in an environment free of the top four human, dog, and cat food allergens (cow milk, wheat, soy, and corn), which are also providing major quantities of allergens, damaging lectins, estrogens, depressants (casomorphins/gliadomorphins), and excitotoxins. Do you think you might just start feeling better??? (Smile)

But there’s more good news (and this is the main reason for placing this information here on this page). Once you have recovered…your brain, liver, and immune system are back to normal or close to it…then you can go back to eating some of those sources of glutamate and aspartate that are not one of the “big 4”. Again, the reason for the more severe restriction of these other foods was to place a Band-Aid on the situation- to provide relief for your ailing brain and liver (which regulates the glutamate in the bloodstream) by reducing the load of these potentially harmful neuroactive amino acids on these unhealthy organs. Once the nervous system and liver have recovered, most of us can go back to eating the nuts, seeds, beans, and meats that we were limiting in the beginning.

Just remember- "Everything in moderation". Some individuals will recover to such a degree that they could go back to eating all of the peanuts, lima beans, and steak they want without experiencing a seizure, pain episode, or bad night's sleep. BUT, most will fall into a category somewhere in between this level of recovery and where they were to start with, depending on several secondary factors, such how much we cheat with the "big 4", our age, local pollution, and more. And after all, loading up on peanuts is not good for anyone. (All you need is about 6 peanuts or almonds to get all that you need from them for the day. BUT, who does that???) Similarly, we do not need the cowboy-sized serving of steak they throw at us at your favorite restaurant. (I have to keep telling myself that.)

So, please do not think that I am saying you cannot eat any of the foods on the glutamate-rich list ever again. The formal name of the diet is the glutamate-aspartate restricted diet. That is a relative term, with some individuals requiring a more severe restriction than others. But when it comes to the "big 4", I use the term elimination. If you are gluten, casein, soy, and/or corn intolerant, elimination is the key to your optimal recovery. These are the guys that set us up for all of this mess. That is why I now "lovingly" call them the four horsemen of the apocalypse. The effects they can have on man and animals is potentially catastrophic and hopefully the reader now has a much better idea of why I have dedicated my life to this mission.

I hope this helps.

Dogtor J.

Neurotransmitter Levels Predict Post-Traumatic Stress

TUESDAY, Aug. 29 (HealthDay News) -- Blood levels of the neurotransmitter gamma-aminobutyric acid, or GABA, in trauma patients may predict the development of post-traumatic stress disorder (PTSD), according to the results of a study of car-accident victims published in the August issue of the American Journal of Psychiatry.

Guillaume Vaiva, M.D., Ph.D., of the University of Lille II, School of Medicine in France, and colleagues measured GABA blood levels in 78 car-accident victims who had been admitted to trauma centers and hospitalized for at least three days.

After one year, the researchers found that 80 percent of patients whose post-trauma GABA levels were below 0.2 mmol/ml met all or most of the criteria for PTSD and that two-thirds of them also met criteria for major depressive disorder. Among patients who met all or most of the criteria for PTSD at six weeks, they also found that 75 percent of those whose post-trauma GABA levels were above 0.2 mmol/ml no longer met criteria for PTSD after one year.

"From a clinical perspective, it would be extremely helpful to predict with reasonable accuracy which trauma patients are at risk of having chronic PTSD," the authors conclude. "Our results, if replicated, would suggest that a plasma GABA level greater than 0.2 mmol/ml may protect against chronic PTSD and may represent a marker of recovery among patients who have suffered trauma."

This article: Copyright © 2006 ScoutNews, LLC. All rights reserved.

Woody McGinnis' notes on ADHD and nutrients. Includes suggested supplements

Physical Health Profile in ADHD

1. Gastrointestinal Abnormality

• Colicky Infants and Older Children Diarrhea-Prone (V Colquhoun HACSG, Sussex UK 1987)
• Severe Stomach Aches (Am J Clin Nutr 1995; 62:761-8)
• Elevated Stool Creosols (Lancet 7.12.85)
• Ileal Lymphoid Nodular Hyperplasia (Lancet, July 18, 1998)
• Urinary Peptide Elevations-P. Shattock and A. Broughton
• Urinary Organic Acids Elevations- W. Shaw
• IAG Elevations-A. Broughton
• Parasitosis 67%-M. Lyon and J. Cline

2. Compromised Immunity

• More Infections and Antibiotics (Am J Clin Nutr 1995; 62: 761-8)
• Low Complement C4B (J Am Acad Child Adolesc Psych 1995; 34(8): 1009-14)

3. Detoxification Weakness

• Low-Level Lead Exposure Induces Hyperactivity in Rats (Science 182(116): 1022-1024
• Marked Improvement in 7 of 13 Chelated for "Non-Toxic" Lead Levels (A J Psych 1976 133(10): 1155-1158)
• Neonatal and Maternal Hair Lead Predict LD at Age 6 (Lancet 2:285 1987)
• Hair Lead Levels Correlate with Teacher-Rated and Physician-Diagnosed ADHD (Arch Environ Hlth 1996; 51(3): 214-20)
• Striking Chelation Results in 50 Vancouver Children (Turning Lead into Gold, paperback, Nancy Hallaway and Ziggert Strauts 1996)

4. Abnormal Nutritional Profile In ADHD

• Zinc Deficiency
  • Lower urinary, serum, nail and hair zinc than controls plus quick drop in serum and salivary zinc with double-blind tartrazine. United Kingdom. (J Nutr Med 1:51-57, 1990)
  • Plasma, erthrocytes, urine and hair lower than controls. Poland (Psychiatr Pol 28(3):345-53 1994)
  • Zinc deficiency in attention-deficit hyperactivity disorder. Israel. (Biol Psychiatry 40(12):1308-10 1996)
  • Serum zinc--and free fatty acids--lower. Turkey. (J Child Psychol Psychiatry 37(2):225-7 1996)
  • In vitro study demonstrates decreased loss of fatty acids from mesenteric phospholipids with perfusion of physiological zinc. Canada. (Can J Physiol Pharmacol 68(7): 903-907 1990)

• Fatty Acid Deficiency
  • Lower serum DHA, DGLA and AA in hyperactives than controls. (Clin Pediatr 26(8):406-411 1987)
  • Double-blind administration of evening primrose oil to a subgroup of prior study was associated with improved parent ratings for Attention and Excess Motor Activity compared to placebo. (J Abn Child Psychol 15(1): 75-9 1987)
  • Evening Primrose oil (GLA) 1 gram/day improved 53 of 79 hyperactive children selected as a subgroup on the basis of mood swings. The most striking improvement was noted in children with sleep disorders, crying spells and family history of alcohol or bipolar. (Muriel Blackburn, Crawley Hospital, Sussex , U.K.)
  • Lower plasma DHA, EPA and AA, and lower RBC AA in ADHD than controls (Am J Clin Nutr 62: 761-8 1995)
  • (Same group above correlated greater tendency to behavioral problems with lower total plasma Omega-3, more colds and antibiotics with lower total Omega-6. Physiology and Behavior Vol 59, Nos. 4/5 915-920 1996)
  • Zinc and Evening Primrose Oil the mainstay for thousands of successes claimed by the HACSG, Sussex England (Personal Communication, Vicky Colquhoun 1997)

• Magnesium Deficiency
  • Magnesium deficiency measured in 95% of 116 Polish children with ADHD: 78% low hair, 59% low RBC's, 34% low serum. (Magnesium Research 10(2): 143-148 1997)
  • Double-blind adminstration of 200 mg elemental magnesium per day to 25 of the above group produced measurable decrease in hyperactivity over 6 months compared to control. (Magnesium Research 10(2): 149-156 1997)

• Iron Deficiency
  • Preliminary study showed improved behavior in nonanemic hyper-actives given 5 mg/kg/day of Iron for 30 days, with significant increase in serum ferritin. (Neuropsychobiology 1997; 35(4):178-80)
  • Lower Iron plasma, RBC, Urine and Hair levels in 50 Hyperactives (Psychiatr Pol 1994; 28(3): 343-53)

• Calcium Deficiency
  • Plasma, RBC, urine and hair Calcium in 50 hyperactive Polish children lower than controls. (Psychiatry Pol 1994; 28(3):

• B6 in ADHD
  • B6 to hyperactives with low serotonin levels resulted in normal serotonin levels and behavior. (Pediatrics 55: 437-41, 1975)
  • B6 to 6 hyperactives with low serotonin levels increased serotonin and reduced hyperactivity better than Ritalin in double blind cross-over. Benefit carried over into the following placebo period, but not with Ritalin. (Biol Psychiatry 14(5):741-51 1979)
  • Significant subgroup of patients with ADHD (and Autism) found to have pyrroluria by Bill Walsh (Pfeiffer Treatment Center, Napperville, IL) and Hugh Riordan (BioCenter, Wichita KS). Good clinical track record for response to generous B6 and Zinc in thousands of pyrroluric patients. (Walsh also finds Biotin very useful in "slender malabsorber group")

• B12 in ADHD
  • Elevated urinary methylmalonic acid and early reports of response to oral B12 from John Linnell, research director at The Children's Medical Charity, U.K. Some reports of response to B12 shots.

Emerging Possibilities

• VITAMIN A HYPOTHESIS- M Megson
• CALCIUM DYSREGULATION HYPOTHESIS-W McGinnis

Interventional Strategies for Behavioral Children

1. OPTIMIZE NUTRITION

• Low Glycemic
• Big Breakfast, Protein First, Frequent Meals
• Good Fats
• No Excitotoxins
• Organic as Possible
• Plenty of Fiber
• Careful with the Copper

• Baseline CBC, UA, Thyroid
• Urinary pyrrole
• RBC Fatty Acid Analysis
• Hair Mineral Analysis/Other Mineral Studies
• (PHF)

Start with these incrementally, continue until proven otherwise:

• Zinc with Manganese
• B6 (and/or P-5-P) with Magnesium
• Calcium
• Vitamins C and E

Then Address Fatty Acids

• Evening Primrose for GLA (Careful Seizures or Asthma)
• Cod Liver Oil (Provides Vit A and D plus EPA/DHA)
• Fish Oil or Neuromins for additional Omega 3

Other: B12, Biotin, Taurine, MSM, Folate, DMG, Amino Acids, Mb, Fe

2. ADDRESS OVERGROWTHS AND GUT CARE

• O&P at a bare minimum
• Urinary Organic Acids

• Nystatin/Oral Amphotericin/Diflucan/Cranberry/Grapefruit Seed

• Reconsider NSAIDS
• Fiber/FOS/Glutamine/Glucosamine
• Pentosan Polysulphate ("Elmiron")?
• Re-populate bowel with probiotics
• Creon or other digestive enzymes

3. ADDRESS FOOD INTOLERANCES

• IgG food antibody blood testing

• Urinary Peptides
• Address lactose, phenolic and high-arabinose intolerance.

Oxytocin and behavior

http://www.healing-arts.org/children/autism-overview.htm Oxytocin is produced through the influence of the cholecystokinin-A (CCKA) receptor, which requires its substrate, cholecystokinin, to be sulfated (see the free sulfate theory of autism). If there is insufficient ability to sulfate compounds (a finding in some autistic people), the receptor will not work well, and many CCKA mediated functions will be afffected. The presence of opioid peptides and opiate receptors in the hypothalamo-neurohypophysial system, as well as the inhibitory effects of enkephalins and beta-endorphin on release of oxytocin and vasopressin has been well documented 6. Opioid peptides inhibit oxytocin release and thereby promote the preferential secretion of vasopressin when it is of functional importance to maintain homeostasis during dehydration and hemorrhage. Both neuromodulators and a neurohormones co-exist in the same neuron, as demonstrated for vasopressin with dynorphin or leucine-enkephalin, which serves to regulate the differential release of two biologically different, yet evolutionarily-related, neurohormones, e.g. oxytocin and vasopressin, from the same neuroendocrine system. Stress: Human immune function is mediated by the release of cytokines, nonantibody messenger molecules, from a variety of cells of the immune system, and from other cells, such as endothelial cells. There are Th1 and Th2 cytokines. Autoimmune and allergic diseases involve a shift in the balance of cytokines toward Th2. The autoimmune aspect of autism has been related to excessive Th2 cytokines resulting, in part, from vaccination. Gulf War syndrome and asthma have been similarly linked to excess immunization in the presence of increased environmental toxins and pollutants (high antigenic load). http://www.healing-arts.org/children/index.htm Please also see our new article, "Imaging Children with ADHD: MRI Technology Reveals Differences in Neuro-signaling". In this report, it was found that children with attention deficit-hyperactivity disorder (ADHD) may have significantly altered levels of important neurotransmitters in the frontal region of the brain, according to a study published in the December 2003 issue of the Journal of Neuropsychiatry and Clinical Neurosciences. "Our data show children with ADHD had a two-and-half-fold increased level of glutamate, an excitatory brain chemical that can be toxic to nerve cells," said lead author Helen Courvoisie, M.D., assistant professor, division of child and adolescent psychiatry, department of psychiatry and behavioral sciences at the Johns Hopkins Medical Institutions, Baltimore. "The data also suggest a decreased level of GABA, a neuro-inhibitor. This combination may explain the behavior of children with poor impulse control." Environmental factors associated with ADHD include low birth weight, hypozia (too little oxygen) at birth, and exposure in utero to a number of toxins including alcohol, cocaine, and nicotine. Other studies have found correlations between certain toxic agents / nutrient deficiencies and learning disabilities. These include: * Calcium deficiency * High serum copper * Iron deficiency can cause irritability and attention deficits * Magnesium deficiency, which is characterized by fidgeting, anxiousness, restless, psycho- motor inability, and learning difficulties * Malnutrition in general is related to learning disabilities; the child does not have to look malnourished, a fact forgotten in affluent countries * Dyslexic children seem to have abnormal zinc and copper metabolism - low zinc and high copper * Iodine deficiencies have been linked to learning difficulties http://osiris.sunderland.ac.uk/autism/owens.htm CHOLECYSTOKININ Lack of availability of sulfate would also seriously effect the performance of the major gut hormone and neurotransmitter called cholecystokinin. Two types of CCK receptors have been described: the first one, the CCKA receptor, is predominant in the alimentary canal; and the second, the CCKB receptor, is more abundant in the brain. Both receptors are found in both systems, however, and can be co-localized. (95,70) Many forms of CCK are active, but the octapeptide form of CCK which is a chain of eight amino acids, is able to promote the same degree of signal at the CCKB receptor regardless of whether sulfate has attached to it or not. On the other hand, the CCKA receptor is a thousand times more responsive to sulfated octapeptide than it is to the octapeptide's unsulfated form. (44,23) In a condition of low sulfate, CCK's maturation might be affected (24), and the delivery of its signal at the CCKA receptor would be unreliable.When one looks at the function of the CCKA receptor, the possible relevance to autism begins to become clear. Though it is clear there are some regions where the CCKA receptor does not regulate the production of serotonin, it clearly does have effects in the hypothalamus (34,56), and it is also clear that CCK has very powerful effects on serotonin in other regions where the receptor has not been differentiated. It may consequently have effects on serotonin's metabolite, melatonin, in the pineal gland. The CCKA receptor powerfully regulates dopamine(23,92,117); and also intrinsic factor (114), a substance in the digestive system which allows the body to absorb B12. When B12 is lacking it will result in elevations in methylmalonic acid in the urine (31), which was found to be consistently elevated in the children in Wakefield's recent study.(119) Dysregulation of these pathways in autism have been described by others. (7,82) The CCKA receptor also governs the release of oxytocin (64), dubbed "the social hormone" whose inadequacy may relate to the social deficits in autism. http://209.85.165.104/search?q=cache:NxDcVeCDi1EJ:www.eas.asu.edu/~autism/Additional/SummaryofDefeatAutismNow.doc+zinc+CCK+oxytocin&hl=en&ct=clnk&cd=3&gl=us Sulfation: Susan Owens substituted for Rosemarie Waring, and presented Dr. Waring's data on sulfate in autism. Basically, people with autism were found to excrete roughly twice as much sulfate in their urine, so that they had only 1/5 the normal level of sulfate in their bodies. Sulfur is an essential mineral, and is needed for many functions in the body. AIDS patients have also been found to exhibit a loss of sulfur in their urine, leading to a loss of extracellular sulfated structures in the brain. This has not yet been investigated in autism, but may be the same. In AIDS patients, treatment with N-acetyl cysteine was found to be beneficial. In autism, TNF (tumor necrosis factor) is elevated, which can inhibit the conversion of cysteine to sulfate. Low sulfur levels could cause many problems. o Sulfur is needed to sulfate the hormone CCK, which stimulates oxytocinergic neurons to release oxytocin. So, a lack of sulfur could explain the low oxytocin levels found in autism, which is important for socialization. o Sulphate is important for detoxification of metals and other toxins. o Sulphation requires activated sulfate, which requires magnesium. o Boys excrete more sulfur than girls, so they may be more susceptible to sulfation problems. o Wakefields group found that the ileum of the intestine lacks sulfur, which would lead to a leaky gut. o Sulphate is needed to release pancreatic digestive enzymes. o Many enzymes would be impaired if sulfur levels were low. o The perineuronal nets around neurons, which modulate their function, are primarily composed of chondroitin sulfur. Low sulfur would thus yield less modulation of neurons o The hepatitis B vaccine was found to inhibit sulphation chemistry for one week in typical people.

Problem with FD&C Blue Dye #1?

SUMMARY OF REPORTS

• As of September, 2003, the FDA is aware of 20 cases from the scientific literature or in FDA post-marketing adverse event reports associating the use of blue dye in tube feedings with blue discoloration of body fluids and skin, as well as more serious complications. There have been 12 reported deaths and one case with an unknown outcome.
• In more than 75% of all reported cases, patients had a reported history of sepsis (and therefore likely altered gut permeability) before or during systemic absorption of Blue 1.
• Time of onset of toxicity from first use of Blue 1 varied from several hours to 20 days of continuous use in enteral feedings.

At this time, the FDA believes practitioners should be aware of the following points:

• Use of Blue 1-tinted enteral feedings for detecting aspiration has been associated with several serious adverse events, including death, although a direct causal relationship has not been definitely established.
• The safety of Blue 1-tinted enteral feedings for detecting aspiration has not been documented.
• Based on the reports received to date, patients at risk for increased intestinal permeability, which includes those with sepsis, burns, trauma, shock, surgical interventions, renal failure, celiac sprue, or inflammatory bowel disease, appear to be at increased risk of absorbing Blue 1 from tinted enteral feedings.
• In addition to the possibility of systemic toxicity, Blue 1-tinted enteral feedings may interfere with diagnostic stool examinations, such as the hemoccult test.
• Other blue dyes, such as methylene blue and FD&C Blue No. 2, may have similar if not greater toxicity potential than Blue 1 and would not be appropriate replacements.

Which Supplements Help Which Issues?

From the TacaNow site.

Phosphatidyl choline is also very effective in protecting DHA/EPA from free radical oxidative stress..... another good reason to take it. In my experience DMAE is especially effective for increasing acetylcholine levels in the brain, since it passes the blood/brain barrier & converts to choline. I like to use this for overmethylated persons who have excessive dopamine and norepinephrine levels. However, enhancing acetylcholine activity must be avoided in persons who genetically are overloaded in this NT. Choline, DMAE, and phosphatidyl choline can cause nasty symptoms in these persons (about 10% of the population). Persons with innately high acetylcholine levels tend to be very terse and sometimes nearly catatonic. They have very high anxiety, but usually keep it inside. They also usually have a history of seasonal allergies, perfectionism, and OCD tendencies. Increasing acetylcholine activity can be a disaster for them. Those deficient in acetylcholine usually present with nervous legs, are prone to pacing, and are quite voluble. Their misery is plain to everyone. Therapies to increase acetylcholine activity can be extraordinarily helpful for this population. (March 6, 2003)

Blog entry about histamine/PST/supplements for methylation

Found this on a blog by a Pfeiffer patient. Interesting. Sulfation Sulfation is the conjugation of toxins with sulfur-containing compounds. The sulfation system is important for detoxifying several drugs, food additives, and, especially, toxins from intestinal bacteria and the environment. In addition to environmental toxins, sulfation is also used to detoxify some normal body chemicals and is the main pathway for the elimination of steroid and thyroid hormones. Since sulfation is also the primary route for the elimination of neurotransmitters, dysfunction in this system may contribute to the development of some nervous system disorders.

Sulfation was already on my list on "to learn about" since the PTC prescribed phenolic enymes, which break down phenols, which are ordinarly broken down by sulfates. Maybe I was too hasty in the "phase II ok for histapenics" conclusion. Still, methionine is needed for sulfation, and supposedly histapenics have a lot of that. I dont know. Inducers of phase II detoxification enzymes Glutathione conjugation: Brassica family foods (cabbage, broccoli, Brussels sprouts); limonene-containing foods (citrus peel, dill weed oil, caraway oil) Amino acid conjugation: Glycine Methylation: Lipotropic nutrients (choline, methionine, betaine, folic acid, vitamin B12) Sulfation: Cysteine, methionine, taurine Acetylation: None found Glucuronidation: Fish oils, cigarette smoking, birth control pills, Phenobarbital, limonene-containing foods Inhibitors of phase II detoxification enzymes Glutathione conjugation: Selenium deficiency, vitamin B2 deficiency, glutathione deficiency, zinc deficiency Amino acid conjugation: Low protein diet Methylation: Folic acid or vitamin B12 deficiency Sulfation: Non-steroidal anti-inflammatory drugs (e.g. aspirin), tartrazine (yellow food dye), molybdenum deficiency Acetylation: Vitamin B2, B5, or C deficiency Glucuronidation: Aspirin, probenecid reads like a checklist of histapenic supplments, but do not taht ciggarettes, most favored by histadelics, induce phase II detoxification. Pahse III is bile production. Bile. from the liver, stored in the gall bladder. Somehow I recall that Ceruplasmin is involved. I have to check that out.

Impairment of bile flow within the liver can be caused by a variety of agents and conditions. These conditions are often associated with alterations of liver function in laboratory tests (serum bilirubin, alkaline phosphatase, SGOT, LDH, GGTP, etc.) signifying cellular damage. However, relying on these tests alone to evaluate liver function is not adequate, since, in the initial or subclinical stages of many problems with liver function, laboratory values remain normal. Among the symptoms people with enzymatic damage complain of are: Fatigue; general malaise; digestive disturbances; allergies and chemical sensitivities; premenstrual syndrome; constipation.

Hmmmmmmmm. My PMS is fine, but that is interesting. AS noted above, my AST and SGOT are always slightly elevated, and my billirubin is high. If this researches leads to something, I want a refund from all the hospitals who have wasted my time on cr*p I could figure out. I am sick of funding thier student loan payments.

regrettably methionine is listed as the only supplment aiding in bile production, but I have to tell you that I am recently feeling like the methionine and methly cycle is more complex than the PTC is telling me. I dont know on that one.

Symptoms of Gluten Intolerance

Is Subclinical Gluten Intolerance/Celiac Disease Sabotaging Your Health? The Celiac Disease/Autoimmune/Thyroid Connection

Gluten intolerance -- also known as celiac disease, celiac sprue, and sprue -- is a genetic autoimmune condition that makes it difficult for the body to properly absorb nutrients from foods. It affects an estimated 1.5 million Americans. What happens in gluten intolerance is: The body lacks a particular digestive enzyme, intestinal glutaminase, that can digest gluten products Gliadin antibodies are produced as the body's reaction to the presence of the gluten the villi in the bowels become flattened, making them less able to sweep along waste products and filter out toxins The bowel, in a state of irritation, becomes more permeable, allowing larger proteins to pass through, which further aggravates the "allergic" response The body responds by producing more histamine, seratonin, kinins, prostaglandins, and interleukins -- which can trigger or aggravate autoimmune and inflammatory conditions The incidence of full-scale gluten intolerance has been found to be substantially higher in people with autoimmune thyroid disease. A study reported on in the February 2000 issue of Digestive Diseases and Sciences found that undiagnosed celiac disease may be part of the process that triggers an underlying autoimmune disease. In their findings they wrote: ""We believe that undiagnosed celiac disease can cause other disorders by switching on some as yet unknown immunological mechanism. Untreated celiac patients produce organ-specific autoantibodies." Of perhaps greatest importance to thyroid patients, those researchers found that the various antibodies that indicate celiac disease - organ-specific autoantibodies (i.e., thyroid antibodies) -- disappear after 3 to 6 months of a gluten-free diet. The researchers suggested that patients with autoimmune thyroiditis "may benefit from a screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders." Celiac antibodies blood testing can help diagnose the full-scale version of the condition, but formal diagnosis requires biopsy. Because the full-scale diagnosis of the condition is not that common, many doctors and patients do not realize that a milder version of the condition -- subclinical gluten intolerance/celiac disease -- may be the cause of chronic symptoms in millions more thyroid patients. Diagnosing the subclinical, reversible version requires newer "intestinal permeability" or "mucosal barrier" tests, along with clinical observation of symptoms made by an experienced practitioner. What are the symptoms of subclinical gluten intolerance and celiac disease? Recurring abdominal pain and bloating Gas, intestinal difficulties Aggravated allergies Difficulty losing weight Muscle aching Joint stiffness and pain, especially in hands, with swelling Fatigue Burning sensations in the arms and legs Numbness and tingling in hands, arms and legs Brain fog, memory problems, disorganized thinking Sores inside the mouth Painful skin rash on elbows, knees, and buttocks Hives Once diagnosed, the next step is a gluten-free diet. The Gluten Free Diet (Featuring information from the federal government's NIDKK site) The only treatment for celiac disease is to follow a gluten-free diet--that is, to avoid all foods that contain gluten. For most people, following this diet will stop symptoms, heal existing intestinal damage, and prevent further damage. Improvements begin within days of starting the diet, and the small intestine is usually completely healed--meaning the villi are intact and working--in 3 to 6 months. (It may take up to 2 years for older adults.) The gluten-free diet is a lifetime requirement. Eating any gluten, no matter how small an amount, can damage the intestine. This is true for anyone with the disease, including people who do not have noticeable symptoms. Depending on a person's age at diagnosis, some problems, such as delayed growth and tooth discoloration, may not improve. A small percentage of people with celiac disease do not improve on the gluten-free diet. These people often have severely damaged intestines that cannot heal even after they eliminate gluten from their diets. Because their intestines are not absorbing enough nutrients, they may need to receive intravenous nutrition supplements. Drug treatments are being evaluated for unresponsive celiac disease. These patients may need to be evaluated for complications of the disease. If a person responds to the gluten-free diet, the physician will know for certain that the diagnosis of celiac disease is correct. A gluten-free diet means avoiding all foods that contain wheat (including spelt, triticale, and kamut), rye, barley, and possibly oats--in other words, most grain, pasta, cereal, and many processed foods. Despite these restrictions, people with celiac disease can eat a well-balanced diet with a variety of foods, including bread and pasta. For example, instead of wheat flour, people can use potato, rice, soy, or bean flour. Or, they can buy gluten-free bread, pasta, and other products from special food companies. Whether people with celiac disease should avoid oats is controversial because some people have been able to eat oats without having a reaction. Scientists are doing studies to find out whether people with celiac disease can tolerate oats. Until the studies are complete, people with celiac disease should follow their physician or dietitian's advice about eating oats. Plain meat, fish, rice, fruits, and vegetables do not contain gluten, so people with celiac disease can eat as much of these foods as they like. Examples of foods that are safe to eat and those that are not are provided below. The gluten-free diet is complicated. It requires a completely new approach to eating that affects a person's entire life. People with celiac disease have to be extremely careful about what they buy for lunch at school or work, eat at cocktail parties, or grab from the refrigerator for a midnight snack. Eating out can be a challenge as the person with celiac disease learns to scrutinize the menu for foods with gluten and question the waiter or chef about possible hidden sources of gluten. However, with practice, screening for gluten becomes second nature and people learn to recognize which foods are safe and which are off limits. A dietitian, a health care professional who specializes in food and nutrition, can help people learn about their new diet. Also, support groups are particularly helpful for newly diagnosed people and their families as they learn to adjust to a new way of life.

ADDers Are More Likely to Have Fatty Acid Deficiencies

Omegas and ADD A Purdue University study showed that kids low in Omega-3 essential fatty acids are significantly more likely to be hyperactive, have learning disorders, and to display behavioral problems. Omega-3 deficiencies have also been tied to dyslexia, violence, depression, memory problems, weight gain, cancer, heart disease, eczema, allergies, inflammatory diseases, arthritis, diabetes, and many other conditions. Over 2,000 scientific studies have demonstrated the wide range of problems associated with Omega-3 deficiencies. The American diet is almost devoid of Omega 3's except for certain types of fish. In fact, researchers believe that about 60% of Americans are deficient in Omega-3 fatty acids, and about 20% have so little that test methods cannot even detect any in their blood. Your brain is more than 60% structural fat, just as your muscles are made of protein and your bones are made of calcium. But it's not just any fat that our brains are made of. It has to be certain types of fats, and we no longer eat these types of fats like we used to. Worse, we eat man-made trans-fats and excessive amounts of saturated fats and vegetable oils high in Omega-6 fatty acids, all of which interfere which our body's attempt to utilize the tiny amount of Omega-3 fats that it gets. Other parts of our bodies also need Omega-3 fatty acids. Symptoms of fatty acid deficiency include a variety of skin problems such as eczema, thick patches of skin, and cracked heels. In the fall of 1998, after reading about the Purdue study which associated fatty-acid deficiencies with learning disorders and hyperactivity, I began to give my six-year son a tablespoon of Barlean's Flax Oil each day, and I took the same amount myself (mixed with yogurt). Flax oil is extremely high in Omega-3's. I also reduced our consumption of trans-fats and increase the amount of olive and canola oil in our diet. After one month, the incurable eczema located on the back of my son's legs vanished, and it is still gone as of this writing (5/99). That eczema had not responded to diet changes, cremes, or allergy medication, and he'd had it for years, so bad that he would scratch it until it bled and caused him to lose sleep. Then, during the next three months my cracked heels slowly improved until they too were cured. Like my son's rashes, my cracked heels had not responded to any type of treatment for several years, even though I tried lotions and pumice stones to thin the skin. Today, they are fine. I can only imagine what the fatty-acid deficiency we clearly both had had was doing to me and my son neurologically, and I am grateful to have learned about it. My son has been doing great in Kindergarten with very few behavior problems, and is ahead of his peers in reading, so I can't help but wonder if the increase in Omega-3 fatty acids is a factor in that. While I'll never know for sure, I suspect that it was. Signs of Fatty Acid Imbalance (from the book "Smart Fats") Dry skin Dandruff Frequent urination Irritability Attention deficit Soft nails Alligator skin Allergies Lowered immunity Weakness Fatigue Dry, unmanageable hair Excessive thirst Brittle, easily frayed nails Hyperactivity "Chicken skin" on backs of arms Dry eyes Learning problems Poor wound healing Frequent infections Patches of pale skin on cheeks Cracked skin on heels or fingertips Imagine your brain conducting some routine maintenance on your dopamine and serotonin receptors (implicated in both ADD and mood disorders). These receptors are composed of an Omega-3 fatty acid called DHA. If you don't have much DHA in your blood, man-made trans-fat molecules may be used as a construction material instead. But trans-fats (hydrogenated oils) are shaped differently than DHA: they are straight while DHA is curved. The dopamine receptor becomes deformed and doesn't work very well. Repeat this scenario day after day, year after year, and you could wind up with problems like depression and problems concentrating. This problem is most severe for a child whose brain is still developing. "A lack of highly unsaturated fats is particularly noticeable in connection with brain and nerve functioning. An adjustment in diet to one with oil and protein contents high in unsaturated fats brings the best results in children. I have often observed this when called in to treat cancer patients. In general, I recommend that the whole family adjust their food intake so that they use the optimal, natural fats. As for children whose scholastic performance is often below standard -- and it's usually the case in families where the parents don't eat correctly -- the results of an optimal fat intake normally begin to show themselves in school marks being bettered by not only one, but two levels." - from "Flax Oil as a True Aid..." by Dr. Johanna Budwig, a seven time nobel prize nominee and considered by many to be the foremost authority on fats & healing, 1959. Now imagine a child in school learning math. The act of learning requires the brain to form new neural pathways. DHA is needed, especially for the delicate neural synapses which are composed entirely of DHA. This child, like the vast majority of U.S. children, eats almost no Omega-3 fatty acids. What does the brain do? Again, it struggles and finally uses other types of fats, which are the wrong shape. The neural network develops slowly and is defective. The child has learning and memory problems as well as behavior problems. "The Link Between Omega-3 Fatty Acids and Learning (from "The Omega Plan") "In a study of learning ability, rats were raised on either a diet that was deficient in Omega-3 fatty acids or one that was nutritionally complete. Initially, both groups of rats had similar numbers of synaptic vesicles. After a month-long learning program, however, the Omega-3 enriched rats had considerably more vesicles in their nerve endings and also performed markedly better on the tests. This study suggests there may be a direct connection between the amount Omega-3 fatty acids in your diet, the number of synaptic vesicles in your neurons, and your ability to learn." I believe that within the next 5 or 10 years the population at large will become familiar with the issue of fatty acid deficiency and the harm causes by transfats, and there will be significant changes in the way food is formulated and marketed. In 1994 the Center For Science in the Public Interest petitioned the FDA to require labeling of transfats. In 1998 Consumer Reports called for similar labeling (Nov. 98 issue). In response to growing pulic pressure and the rising number of studies implicating transfats, the FDA has announced a new rule that will require the transfat content of foods, but it won't become effective for a few years. Companies are beginning to market omega-3 foods, like tuna and eggs from chickens fed with high-omega 3 foods. Babyfood companies like Gerber are talking about adding DHA to foods (meanwhile the same food still contains transfats). In Japan parents have been giving their kids DHA supplements for years to improve their grades. "Struggling With Jamie" From "Smart Fats" by Michael Schmidt "Jamie was a ten-year-old boy who seemed to struggle with behavioral problems almost from the beginning. He was inattentive, aggressive, and had difficulty with coordination. Sports were hard for him and learning was no better... Jamie also had patches of dry skin and coarse, unruly hair -- clues to fatty acid imbalance. Jamie began taking a balanced fatty acid supplement that contained DHA, GLA, and ALA from DHA oil, primrose oil, and flax seed oil respectively. It took roughly six months, but Jamie became "a different child" according to his mother. His balance and motor problems improved along with his behavioral problems." Research has shown that the diets of hunter/gatherers were rich in Omega-3's. They ate a mix of meat, fruits and vegetables, with little or no grains. Green leafy vegetables, certain seeds and nuts, and wild game are rich in Omega-3's. It turns out that cows, chickens and other animals have much higher levels of Omega-3s when they are fed by "free-range" methods because they eat lots of green leafy vegetables. On the other hand, if they are fed grain, their Omega-3 levels crash. Wild game is much healthier to eat and it is much leaner than farm-raised animals. Hunter/gatherers ate greens with lots of Omega-3's. We know this because scientists have actually tested many of the plants and animals eaten by existing and past hunter/gatherer groups. These have been replaced primarily with grains, which contain the wrong kinds of fats. More Detail Than You May Want to Know: EPA, DHA, and the Omega-3 family of Eicosanoids are important types of Omega-3 fatty acids. Normally our body can manufacture all of these products if it has plenty of the parent Omega-3 fatty acid called Alpha-Linolenic Acid (ALA) found naturally in green leafy vegetables, flax, flaxseed and canola oil, walnuts and Brazil nuts. (Note: DHA is not to be confused with DHEA, a popular hormonal supplement). Our bodies convert ALA to EPA; EPA to DHA; and DHA to Omega-3 Eichosanoids. There are many things that can interfere with this process, especially vegetable oils in the diet. Note that it is possible to acquire EPA and DHA directly by eating fish oil, certain eggs, or by taking supplements. Fatty fish contain plenty of both substances. Plenty of studies have shown that fish-eating cultures have much better health, including mental health. DHA is particularly important for brain functions. Scientists have discovered that severely depressed people are lower in DHA, and the more depressed they are, the less DHA they have. One ancient remedy for depression was to feed the patient animal brains, now known to be extremely high in DHA and Omega-3 fatty acids. Incidentally, alcohol is known to deplete DHA stores extremely rapidly. While the body can theoretically manufacture its own DHA out of the parent ALA fatty acid, things can interfere with this conversion. The most important problem is an excess of Omega-6 fatty acids in the bloodstream, which use the same enzymes for a similar type of conversion. This is why it is extremely important not to have too many Omega-6 fats in your diet (the vegetable oils like sunflower and soybean oil). Other problems might inhibit the conversion process, such as a deficiency in certain vitamins and minerals. Infants who are fed formula in the United States receive almost no Omega-3's, while infants who are breast fed thrive on milk rich in DHA (the amount depends on the mother's diet). Researchers have found that infants who are fed formulas enriched with Omega-3's or who are breast fed do better visually and intellectually. Incidentally, pregnant women experience a major loss in DHA as their DHA is rerouted to the fetus. This may be one reason depression is so common after child birth.

How the Opioid Theory Explains Many Maladaptive Behaviors

Worth Reading: One of the main objectives of conferences is that people with differing background and understanding can come together and not only promote their own studies and points of view but also learn from the experience of others. This is particularly important in the study of autism where so many disciplines are involved. Courchesne & Courchesne (1997) discussed this issue with regard to the differing needs of clinicians and practitioners, and scientific researchers and have pointed out the commonalities and dichotomies inherent in their approaches. There is an additional difficulty within the field of autism in that a number of apparently totally different and, at first sight, incompatible sets of understanding and experience are required. Although the syllabi for modern degrees in psychology require a basic appreciation of neurology, graduates cannot be expected to be comfortable with more complex biological and neurological processes. Even worse, those with a physiological or pharmacological training are often dismissive of concepts, which involve measuring elements, which cannot be seen, weighed or quantified by physical methods. One of the most intractable divides, within the field of autism at least, is that which separates brain biochemistry and the psychological theories, which underlie the symptoms by which autism is still defined. This paper represents an attempt to explore some aspect of that gap. Given that no one really understands the neurochemical workings involved in the central nervous system especially when they may well be abnormal, as in the case of autism, the task is a difficult one. The speculations contained in the following pages, are offered and can be accepted as no more than that. Basic Principles a) Biological We subscribe to the opioid excess theory for the causation of autism. The theory has been expounded on a number of occasions (Shattock et al, 1990; Shattock & Lowdon, 1991). In brief, we suspect that peptides and other related compounds, some with opioid (morphine-like) activity, resulting from the incomplete digestion of certain foods in particular gluten from wheat and certain other cereals and from casein from milk and dairy produce, find their way into the bloodstream from the lumen of the intestine. Once in the bloodstream a proportion will cross into the brain. They will either act directly as neuroregulators by mimicking the bodies own natural opioids (such as the enkephalins or endorphins) or act as ligands to the enzymes which would break down these naturally occurring compounds. In either case, the consequence is an increase in opioid and other activities. In the brain the opioids act in a variety of ways at a variety of specific receptors but their effects are basically neuromodulatory. They do not, usually, act as direct neurotransmitters (such as 5-HT (serotonin) or dopamine) but they regulate their activity usually in a diminutive manner. Details will be discussed in the course of the specific examples described later in this paper. b) Psychological There are a number of psychological models, which have been presented as capable of explaining the symptoms of autism. Each theory has its proponents and detractors. Each theory has strengths and weaknesses but it is beyond the scope of this presentation to discuss each of these in detail. In particular, in the UK at least, much attention is given to the “Theory of Mind” deficit ideas (as proposed by Baron-Cohen, Leslie & Frith, 1985) and of “Weak Central Coherence” as advocated by, for example, Hobson (1991; 1995). This study will concentrate upon the ideas of deficits in “Executive Function” as described by Ozonoff (1991) and elaborated by Hughes (1993; 1994; 1996). It is readily conceded that this has been done because the concepts of the theory fit happily with the theories we espouse rather than for any quarrels with the other proposals. Executive Function Deficits There seems, to us, to be one problem inherent with theories based around these concepts: how “autism specific” these deficits would be [see reference]. A case could be made for abnormalities in this process being relevant in many forms of learning difficulty as well as autism spectrum disorders. However, we remain of the opinion that possible links are worthy of exploration. Hughes has listed these deficits as including the following: - planning; - impulse control; - inhibition of pre-potent but incorrect responses; - set maintenance; - organised search; - flexibility of thought and action; - ability to disengage from control by the external context; - ability to guide behaviour by mental models or internal representations. It would seem to us, that these could be summarised in terms of deficits in the process by which the “clever” elements of “the brain” tell the “thick bits” what to do. It is characteristic of scientists, including psychologists (such as Ozonoff and Hughes), to concentrate on some of the more interesting and complex of the deficits which are possible and to ignore some of the very basic systems to which the same principles are known to apply but which would not attract and hold the attention of the trained specialist. We would start by exploring a couple of these simpler systems. 1. Extra-Pyramidal Movements and Dyskinesias One of the features of autism which is well known but which has not been the subject of intensive investigation is the constant movement, which some (but not all) subjects show. Many children appear completely unable to keep still; to sit at a table or to take a meal without standing up and walking around. However much parents and teachers attempt to stop this movement the child will find difficulty. There appears to be a severe, but variable inner drive directed towards this constant movement. To an observer it seems this drive and many of the associated movements are very similar to the constant activity seen in people, diagnosed with schizophrenia but who are taking neuroleptic (anti-dopaminergic) medications. People taking medications such as thioridazine (Melleril), chlorpromazine (Largactil) or haloperidol (Serenace; Haldol) are nearly always given other medications (e.g. orphenadrine (Disipal)) to eradicate or minimise these side effects. It is likely that the movements induced by these medications are in fact the same as those seen in people with autism because they are the result of the same causal mechanism. These neuroleptic drugs act by inhibiting transmission in dopaminergic systems; we are proposing that in autism the dopaminergic system is inhibited not by medications but by the opioid peptides. The consequence is, however, the same. Impulses from the system make use of acetylcholine as their transmitter and such impulses will cause “movement” in many parts of the body. Under normal circumstances, these movements are inhibited by a system (the nigrostriatal system) utilising dopamine as its transmitter. If, therefore, these inhibitory systems are themselves inhibited, the constant movements described above will become evident. The usual medical response is then to give further medications, which are anticholinergic. The phenomenon does bring into question the practice of using neuroleptic drugs, which are basically anti-dopaminergic in their action) in cases where dopaminergic systems are already inhibited. This example is, perhaps, stretching the original description of “executive function” into an area not considered by those who originally proposed the ideas but the principle is entirely analogous. (Medical note: Some neuroleptic drugs, such as haloperidol and sulpiride when used at low doses and risperidone at low or moderate doses, have a selective activity in blocking the pre-synaptic receptors. The net result would be an increase in transmission and amelioration of these particular symptoms) 2) Control of Aggression Being aggressive is “normal” for humans under certain circumstances. Theories of aggression being a basic drive receive support from studies (e.g. Smuts, 1986) showing a biological basis of aggression in other mammalian animals. Whether in response to a stressor (i.e. an aggressive response to a conflict situation), or as a result of frustration (i.e. inability to reach a goal), animal studies have shown that aggression is a primary motivator of behaviour. In humans, the exhibition of aggression is described in many terms, some acceptable and justifiable (e.g. during periods of human conflict as seen in the world wars of the twentieth century) and others deemed socially unacceptable (e.g. committing murder). Often the justification for aggression is defined in terms of factors such as cultural and communicative processes and according to individual perspectives (e.g. attributing the aggressive behaviour of others as being “aggressive” or “assertive” and the aggressive behaviour of ourselves as being “defensive”). Humans need to be prepared to act in this way and the mechanisms to do so are already in place (i.e. fight-or-flight response). However under normal circumstances, they are “inhibited” by other systems and in particular by systems under serotonergic (using serotonin (5-HT) as their transmitter) control. If these systems are themselves inhibited the tendency towards aggressive activity will become evident and more difficult to control. Opioid peptides will inhibit these systems. Diagram of synaptic cleft (Medical note: Drugs such as fluoxetine (Prozac), which increase the availability of serotonin are frequently given to minimise aggression. Eltoprazine is, unfortunately, no longer available but its “serenic” activity is said to be due to its ability to stimulate the postsynaptic receptors. Risperidone will inhibit the presynaptic receptors and so result in a net increase in serotonin availability and decrease in aggression. Note that risperidone will, at appropriate doses, increase dopaminergic transmission in the nigro-striatal system whilst, as the same time, increase serotonergic transmission in these systems. Both of these effects would be predicted as being beneficial.) Taken together these two functions of being primed for immediate movement (dopaminergic system) and being mentally appeared to fight (serotonergic system) are important for the preservation of the individual and normal physiological and behavioural responses to environmental stress. It is well known that under conditions of stress, opioids such as beta-endorphin are released in the brain. These consequences are characteristic of the fear – “fight-or-flight” response and are part of the overall requirement for self-preservation. The same responses would be anticipated as resulting from the presence of opioids from exogenous sources such as food. 3) Sensory Filtration Moving up the scale of complexity from these comparatively simple examples consideration should be given to the effects on sensory systems. The human sensory system comprises of a complex set of devices and channels, which deliver to us the ability to explore the outside world. The properties of this system are made up through a complex association between biological and psychological processes, drawing on information from our five senses and the subsequent coding, organisation and retention of this information. Because of the vast amount of information made available to us from our sensory organs and our finite ability to process this information, we undertake a process of filtration to separate the information, which is meaningful to us from the background information. Cognitive psychological investigation has suggested various theories as to the nature of this filtration process (e.g. Deutsch & Deutsch, 1963; Johnston & Heinz, 1979). Evidence of unusual sensory responses throughout the range of sensory mediums in autism has been catalogued both through psychological research (Courchesne, Akshoomoff & Townsend, 1990) and through various self-report measures by people with autism (Williams, 1996). Studies carried out at the Autism Research Unit have also provided supportive evidence (Taylor, 1998). The presence of opioid peptides will affect transmission in all of the sensory or perceptual systems of the CNS. At the same time as affecting the transmission of signals from the sense organs (sight; sound; gustation; touch; pain; proprioception) these same chemicals will affect the filtration of these signals. As described earlier, under normal circumstances, a perceiver will be able to automatically filter out those sensations which are deemed to be of no interest but which are fairly constant. Thus, the background noise in a classroom or of the traffic; the feel of ones clothing; the constant bombardment by visual stimuli can be ignored and we can concentrate on the task or point of particular interest. In biological terms, this “filtration” is achieved by the intelligent (cortical) areas of the brain sending messages to the more automatic areas to cut down on those impulses. If these inhibitory signals are themselves inhibited then the filtration processes will be inhibited and all of these phenomena will have equal significance. It is not possible to focus on particular areas without unusual effort and concentration. The Attention Deficit Disorder (ADD) problems are explicable in these terms. Similarly, if combined with the problems described above, we would see the additional problems of hyperactivity as shown in Attention-Deficit Hyperactivity Disorder (ADHD) and which so frequently accompany symptoms of dyslexia the symptoms of which are also explicable in terms of perceptual and cognitive abnormalities of this type. 4) Attention Switching Many people with autism have described the difficulties that they experience in switching from one sensory mode to another. For example (Williams 1996), whilst concentrating on processing visual stimuli which may be arriving in overwhelming quantities, they find it difficult, if not impossible, to make sense of auditory inputs. Many people with autism have described themselves as “visual learners” Courchesne (1994), by means of electrophysiological measurements, has provided very convincing evidence that people with autism do have great difficulty in switching their attention from one perceptual mode to another. Once in “visual mode” the time lag before switching to “auditory mode” is very much greater. The control of this switching system could, once again, be described as an “Executive Function” and, once again, could be the consequence of opioid activity within the CNS. 5) Higher Executive Functions The theorists (such as Ozonoff and Hughes) mentioned previously, have concentrated upon activities, which are more complex than the simple examples described here but by extending the explanation to more complex systems one can see how the same principles could apply and how these biochemical abnormalities could result in irregularities in functioning. For example, children with autism find it especially difficult to make choices. When presented with an array of sweets such as is seen in sweet shops and told to choose something the child will appear to “choose” in an arbitrary fashion. Alternatively, (s)he may choose the same thing every time (whether or not (s)he actually likes the chosen entity) or, sometimes, always choose the product nearest to the hand. Making choices is about filtering through options and if, as described above this filtration is affected such processes are far from easy for the subject. Psychologists have drawn attention to the problems people with autism have in planning future activities. Once again, planning involves a consideration of a variety of possible activities. In this case it is even harder than simply choosing sweets as the possibilities are imaginary rather than real. Thus filtering through a range of possibilities; visualising; considering and rejecting possibilities and making choices is asking too much from people where the basic processes are impaired by the presence of these comparatively simple chemicals. Conclusions and General Observations It is not necessary to explain how the other deficits in Executive Functioning, referred to earlier, are explicable in terms of this process but it can be done. In the same way, it may be possible to extend the process further to explain the perceived difficulties in “Theory of Mind” or Central Coherence” tasks. We do not see these psychological abnormalities as being “the cause” of autism although they are sometimes described in these terms. Rather, they are symptoms of underlying psychological abnormalities, which may themselves result, in particular difficulties, which will modify the semi-automatic behaviours described above, or behaviours which are not otherwise directly related to these basic biochemically inspired phenomena. Finally, we totally accept that each person with autism is different. The symptoms described above are superimposed upon the characters of individual human beings who have their own personalities and characteristics, foibles, preferences and inconsistencies. In no way are we attempting to define real people in terms of chemically driven automata. We must also consider how each and every one of us is affected to a greater or lesser extent by such forces, which are difficult to explain. References. Baron-Cohen, S., Leslie, A.M., Frith, U. (1985) Does the Autistic Child have a “Theory of Mind”? Cognition 21: 37-46 Courchesne, E., Akshoomoff, N.A., Townsend, J. (1990) Recent advances in autism. Current Opinion in Pediatrics 2: 685-693 Courchesne, E., Towsend J., Akshoomoff N.A., Saitoh O., Yeung-Courchesne R., Lincoln A.J., James H.E., Haas R.H., Schreibman L., Lau L. (1994) Impairment in shifting attention in autistic and cerebellar patients. Behavioural Neuroscience 108: 848-865 [View Abstract] Courchesne, R.Y., Courchesne, E. (1997) From Impasse to Insight in Autism Research: From behavioural symptoms to biological explanations. Developmental and Psychopathology 9: 389-419 [View Abstract] Deutsch, J.A., Deutsch, D. (1963) Attention: Some theoretical considerations. Psychological Review 70: 80-90 Eysenck, M.W., Keane, M.T. (1993) Cognitive Psychology: A student’s handbook. London (UK), Hillsdale (USA): Lawrence Erlbaum Associates, Publishers Hobson, R.P. (1991) Against the Theory of Mind. British Journal of Developmental Psychology 9: 33-51 Hobson, R.P. (1995) Apprehending attitudes and actions: Separable abilities in early development? Development and Psychopathology 7: 171-182 Hughes, C., Russell, J. (1993) Autistic Children’s Difficulties with Mental Disengagement from an Object: It’s implications for theories of autism. Developmental Psychology 29: 498-510 Hughes, C., Russell, J., Robbins, T.W. (1994) Evidence for Executive Dysfunction in Autism. Neuropsychology 32: 477-492 [View Abstract] Hughes, C. (1996) Brief Report: Planning problems in autism at the level of motor control. Journal of Autism and Developmental Disorders 26: 99-107 Johnston, W.A., Heinz, S.P. (1979) Depth of Non-target Processing in an Attention Task. Journal of Experimental Psychology 5: 168-175 Ozonoff, S., Pennington, B.F., Rogers, S.J. (1991) Executive Function Deficits in High-Functioning Autistic Individuals: Relationship to Theory of Mind. Journal of Child Psychology and Psychiatry 32: 1081-1105 [View Abstract] Shattock, P., Kennedy, A., Rowell, F., Berney, T.P. (1990) Role of Neuropeptides in Autism and their Relationship with Classical Neurotransmitters. Brain Dysfunction 3: 328-45 Shattock, P., Lowdon, G. (1991) Proteins, Peptides and Autism. Part 2: Implications for the education and care of people with autism. Brain Dysfunction 4: 323-334 Shattock, P., Savery, D. (1996) Urinary Profiles of People with Autism: Possible implications and relevance to other research. Conference proceedings from ‘Therapeutic Intervention in Autism’, University of Durham 309-25 Smuts, B.B. (1986) in Atkinson, R.L., Atkinson, R.C., Smith, E.E., Bem, D.J. (eds) Introduction to Psychology (11th edition), p.439. Fort Worth: Harcourt Brace Jovanovich College Publishers Taylor, S.A. (1998) A study of gustational sensitivity using solutions of varying concentrations within a sample of ASD and non-ASD individuals. Conference proceedings from ‘Psychobiology of Autism’, University of Durham. Williams, D. (1996) Autism: An Inside-Out Approach. London, England. Jessica Kingsley Publishers