Good evening, it’s Bill Shaw from MosaicDX (formally the Great Plains Laboratory). Welcome to the webinar on Organic Acid Testing. And there’s a lot of new information, but I always like to share the old information for people who are the veterans.
Webinar Transcript
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History and Expansion of Organic Acid Testing
I’m going to start with a little bit of the history of the organic acids and the organic acid testing started being used in the 1960s onward to determine genetic inborn errors in metabolism. And some of the first that were discovered were phenylketonuria called PKU and methylmalonic aciduria.
And this laboratory has detected these genetic diseases over the years as well. There’s about a hundred laboratories throughout the world who perform this testing, but the vast majority only test for the inborn errors in metabolism, whereas Great Plains has expanded its scope of its testing to include many other factors from the gut and to detect phenomena called dysbiosis or abnormal bacterial overgrowth and vitamin deficiencies and the deficiencies of detoxification compounds like glutathione and many other factors.
Candida and Gastrointestinal Invasion
One of the important factors in many illnesses is the candida.
Candida forms into long colonies called hyphae and these colonies are more invasive. And the reason they’re invasive is because they produce the digestive enzymes at the end of these colonies that make little holes in the mucosa, the lining of the gastrointestinal tract. Candida can affect the lining of the esophagus.
So here’s a picture of an esophagus taken from an endoscope which is inserted into the person’s esophagus showing lots of candida invading the area. I first got into this at the Children’s Hospital finding certain of these chemicals in the organic acid test in two brothers with severe autism. And the upper graph shows the graph of one of the children with autism, the lower graph the normal children.
So you see there’s a quite a big difference in the concentrations of the organic acids in the child with autism. This finding was followed up with a a clinical study involving 23 children with autism who were treated with an antifungal drug. So there was a baseline test and then they were treated with nystatin and we looked to see what happened to the compounds following the use of an antifungal because we suspected that many of these were antifungal compounds.
And we found that seven of the urine markers were significantly higher in the autistic male controls and that a number of these chemicals reduced after antifungal treatment. Also that there was a improvement of the children with autism following the use of antifungals. This is the current organic acid test and you see there’s a number of markers of yeast and fungi that are derived from the intestinal tract.
And in severe cases you’ll find that many or most of these are elevated but most of the time there’s one, two, or three of these markers that are elevated. But they’ve proven to be useful for the presence of candida problems.
Here is a graph (reference in video) from the second publication and here you have the mean and median values of normal male children compared to those with autism.
And the last column is the most significant because you you’ll see that a number of this is taking the autism mean and dividing it by the normal. So what this means is that the mean value of citramalic acid in the autism group was about three and a half times higher than in the normal population. And so for a number of these compounds the autism mean was significantly higher than the normal population, indicating a significant difference.
Behavioral Improvements with Antifungal Therapy
In the popular magazines that some of this information has gotten over, so this was a high-functioning kid with autism and this was the handwriting prior to antifungal therapy and then after antifungal therapy you can see a significant, just after one month of antifungal therapy, a significant improvement in the symptoms. We also include bacterial markers that are very important and some of the markers can be due to both human and bacterial metabolism like succinic acid. So some of them are listed twice.
It can be, so succinic acid can be a mitochondrial marker as well as a marker for bacterial activity. And one of the most important markers for clostridia is HPHPA indicated here. This is one that’s a higher normal value but when the HPHPA is in the abnormal range it’s very significant and I’m going to be talking about new findings with that a little bit later.
And we have a marker for the beneficial bacteria DHPPA as well. I now want to turn to the metabolism of neurotransmitters and even though they’re not the highest neurotransmitters in the brain, two neurotransmitters are extremely important for regulating higher brain activity and those are dopamine and norepinephrine. The word amine comes into play here.
Dopamine has an amine at the end and that’s why it’s called a dopamine. Other things you will see is that it has a ring structure, a six-member ring structure. This is called a, to organic chemists, a benzene ring and it has hydroxyl groups off here that make it a phenolic compound.
This particular chemical grouping can be called a benzene or sometimes you can use the word, the prefix P-H-E-N, phen. So this makes it a phen-ol-amine. So this would be phen for the benzene ring, ol indicating the oxygen and hydrogen and amine.
This is a very important brain catecholamine and it’s broken down to form a compound called DOPAC. You can see the amine was removed right here and replaced by an acid. So this becomes an organic acid and then this can be further metabolized to form a compound called homo-vanillic acid or HVA.
HVA is extremely important because it is the major metabolite of dopamine that can be measured in the urine. So measuring the homo-vanillic acid or HVA is a way of measuring the activity and the production of dopamine in the brain. It’s an indirect way of doing this.
Okay, and now on the next slide, this is a very important concept and the concept is that the dopamine is normally formed from phenylalanine and tyrosine that are present in the diet and virtually all proteins have phenylalanine and tyrosine that can be converted to a compound called DOPA and then to dopamine. And dopamine can then be converted by an additional enzyme that’s present in different brain cells to norepinephrine utilizing an enzyme called dopamine beta-hydroxylase. And the norepinephrine can be monitored by looking at its breakdown product VMA in the urine.
So by measuring HVA and VMA in the urine, you’re getting a view, an overview of the contributions of dopamine to norepinephrine in the brain, with dopamine contributing HVA, norepinephrine contributing VMA. The clostridia bacteria have the ability to convert phenylalanine to other compounds. So for example, phenylalanine, when it’s taken up by clostridium difficile, can be converted to a compound, a phenola compound we’ll call, for creosol, which has the ability to block this particular enzyme.
And other clostridia species, including clostridium difficile, can also convert phenylalanine to form the compound called HPHPA, which is produced by these clostridia in the gastrointestinal tract. So the clostridia are able to produce two different compounds that inhibit dopamine beta-hydroxylase. And as a result of that, if these clostridia species are present, the amount of dopamine becomes much more elevated, and the amount of norepinephrine diminishes significantly.
And this is a very important thing because there are laboratories like neuroscience that give information about these different neurotransmitters, but they don’t measure these compounds produced by clostridia species, so you’re missing this very important information. So if dopamine is elevated, but norepinephrine isn’t, you don’t know what the reason is. Whereas with the Great Plains organic acid test, you get virtually all the same information that the neuroscience lab get, but you get even the more important information, which is that there may be gut bacteria that are inhibiting these pathways and causing severe illness.
So this is showing the same information from a little bit different angle. So the clostridia bacteria is in the gastrointestinal tract, produces certain compounds, the 4-cresol, the HPHBA, and one other that’s also measured on the organic acid, 4-hydroxyphenylacetic. All of these compounds are phenolic compounds that inhibit dopamine, beta-hydroxylase, and as a result of that, dopamine values increase because dopamine accumulates, can’t be converted to norepinephrine, so dopamine increases.
And as dopamine increases, the amount of dopamine converted to its metabolite, HBA, also increases. At the same time, because the conversion of dopamine to norepinephrine is inhibited, the amount of norepinephrine decreases and the conversion of norepinephrine to VMA decreases. What’s a very important thing in this is that these compounds from clostridia may be detoxified by phenylsulfatransferase, and the phenylsulfatransferase is an enzyme that’s frequently deficient in autism and other illnesses as well, perhaps in attention deficit and maybe in many other illnesses, psychiatric illnesses as well.
And this becomes very important if the person is taking acetaminophen, a common pain reliever and anti-fever drug, acetaminophen is broken down and detoxified by this PST enzyme, the phenylsulfatransferase. But if there’s lots of clostridia metabolites present, the acetaminophen will not be detoxified, and under these circumstances, the acetaminophen may be much more toxic. And I think this plays an extremely important role in autism.
As a matter of fact, the combination of these two factors of a child getting acetaminophen when they have low amounts of this enzyme and also having clostridia may be one of the major causes of autism. So, so far, this is…I’ve only mentioned this as a theoretical thing, but this is backed up by the facts. This is an article in one of the European medical journals showing that HVA, the metabolite of dopamine, whoops, need to go back a second, is much more elevated in autism compared to normal control.
So normal individuals have low HVA. We have one little exception here, but you can see the vast majority of people with autism have much higher values. And clinically, there’s a big correlation as well.
What’s been found is that individuals with autism who have the highest level of HVA also have the most severe behavioral abnormalities. So a direct relationship between the amount of dopamine and the dopamine metabolite and the severity of autism. And it was also found that the amount of this enzyme, the dopamine beta-hydroxylase measured in blood samples was lower in those individuals who had severe symptoms of autism.
So we talked about the HVA being high, indicating high dopamine. Why would high dopamine be a problem? Well, high dopamine is a very reactive molecule compared with other neurotransmitters, and it’s converted to oxidative species and free radicals. And this dopamine leaks out of the storage granules that are in neurons or brain cells and leaks into the cytosol.
It undergoes rapid degradation to form the 3,4-dihydroxyphenylacetic acid called DOPAC and HVA, and it also forms hydrogen peroxide, a very oxidative compound via the monoamine oxidation pathway. The dopamine also undergoes oxidation to form superoxide, hydrogen peroxide, and orthoquinone. These are very reactive substances that cause oxidation reactions that can be harmful to the brain cells.
It’s detoxified by reacting with glutathione, and by this reaction, glutathione is used up. So if the person has been subjected to a variety of toxic chemicals, these toxic chemicals will be much more toxic because the excess dopamine has used up the glutathione that is involved in detoxification. And so this excess dopamine can be extremely toxic, and these biochemical abnormalities can cause severe neurodegeneration as these oxidizing species use up glutathione.
So it probably, in some cases, these may cause actual loss of brain cell function if it’s severe enough. So one of the issues that comes up is how reversible are autism. And by the way, I’m using autism as an example, but this takes place in, I’ve seen now, virtually every neurologic and psychiatric disorder.
So this information applies to depression and schizophrenia, obsessive compulsive disorder, Parkinsonism, and seizure disorders. So this very common gut bacteria can have a pronounced effect on psychiatric and neurologic function. And the reversibility of this depends on how long this excess dopamine has been present, how long has it been damaging the brain, how much damage has it done, how many other toxic chemicals the person has been exposed to.
Because if the person has this problem with the excess dopamine and also has other toxic chemicals, the toxicity is going to be more severe. So this is an example of a child with autism, with very severe autism. And you can see here, in blue are the values of HPHPA, and in the red is the amount of dopamine metabolite.
And if you look at these, each of these objects indicates a separate test. So the testing was done about one year apart, and you see when the amount of HPHPA was lower, the amount of HBA is lower. So HBA is on this side and is the…you read from the red graph, whereas the concentration of HPHPA is on the left side when you read it here.
So the important thing is that you see these lines move together, meaning that when HPHPA is high, then HBA becomes high because the HPHPA is inhibiting the dopamine beta-hydroxylase. And this is a child who had severe symptoms and very little speech, and this is a very important aspect that you can see. At this place, the child did not have very much of the Clostridia bacteria, but at a later time, had an extremely elevated amount that would be expected to cause extremely high dopamine to levels that could cause brain damage.
The other thing that shows up as looking at these same dates is that you see as HBA, the dopamine metabolite increases, VMA, which is the neurotransmitter derived from norepinephrine, goes down. And this is exactly what would be predicted by the inhibition of this particular biochemical pathway. So because of that, there’s…dopamine is not converted to…dopamine is not converted to norepinephrine, and so there’s accumulation of dopamine in its metabolite.
HBA and VMA does the opposite, and it decreases. And this is very important as far as behavior because the excess dopamine is also associated with abnormal behavior. In schizophrenia, it could be hallucinations and other abnormalities.
In autism, it could be the stereotypical behavior, repeating the same thing over and over again, whereas the norepinephrine is more involved with learning new things, whereas in autism, there is a tendency to not want to try out new things, to want to stay in the comfort zone, and to repeat the same rituals day in and day out. They…if the person has this clostridia problem when they’re taking a common drug, acetaminophen, one of the common forms of acetaminophen is Tylenol. Acetaminophen or Tylenol is here right in the middle, and there’s four different ways that acetaminophen can be detoxified.
It can have a sugar called a glucuronic acid attached to it, and this process is called glucuronidation. It can have a sulfur atom attached to this hydroxyl group here. So remember that acetaminophen is a phenol, so it’s detoxified by a phenol sulfotransferase.
Rosemary Waring and her research group showed that this pathway is defective in autism. So the individual with autism may not be able to convert acetaminophen to form a non-toxic metabolite very well, but in addition, this pathway is blocked by the number of the clostridia metabolites. So if the person has clostridia problems, already has a weak enzyme for detoxification, then the acetaminophen may form more toxic compounds, and one of the most toxic is called napkin.
It’s a long name. I’m sorry. The napkin is the abbreviation of this very reactive compound that is extremely toxic.
Or the body can detoxify acetaminophen to form aminophenol, which can react with omega-6 fatty acids to form a cannabinoid, which also has the ability to alter behavior. So because of inhibition, because of the presence of clostridia bacteria, they block this reaction. There’s a greater chance that they will convert to form much more toxic products from the metabolic transformation.
So the napkin has the ability to combine with and deactivate multiple proteins, having a sulfhydryl group. It can cause liver damage, and if the amount of napkin gets too high, it can cause death. In addition, the napkin uses up glutathione, so glutathione is not available for detoxing other substances.
Remember, the dopamine itself, which is going to be higher if you have the clostridia problem, is going to be using up the glutathione as well. So you have two different processes that are
using up glutathione. If you have other toxic chemicals you have been exposed to like mercury.
polychlorinated biphenyls or DDT, all of these detox reactions will be impaired because a glutathione is not present in adequate concentrations. So, this is showing the concentration. If you have the clostridia, this is blocked.
You have increasing conversion to more toxic. And you may also have conversion to the increased conversion to glucuronide. But a lot of young children are also deficient in this pathway.
So, if there’s deficiencies both here and here, the only way to detoxify is by going to these more toxic routes of metabolism. So, when you have clostridia, especially when it’s at very high concentration, it produces these excess phenolic compounds, the HPHPA and 4-cresol, as well as another one I mentioned, the parahydroxyphenylacetic. These block the conversion of dopamine to norepinephrine, so there becomes excess amount of dopamine.
And dopamine is a very reactive neurotransmitter that forms free radical oxidative type of compounds and that can be very damaging to the brain in excess. And at the same time, acetaminophen also forms these highly reactive toxic compounds, and napkin being one of the most important. Both of these have a severe negative effect on the brain.
And so, in effect, this combination could be considered the atomic bomb of drug toxicity in the brain, having two different substances that are very toxic, both being produced together, and each one, the napkin blocks, uses up the glutathione, and so it makes the dopamine more toxic and vice versa. So each of the pathways makes the other pathway more toxic. And so here’s the scientific paper indicating that the HPHPA is an abnormal metabolite of phenylalanine and values are elevated in patients with autism and with schizophrenia.
So these bacteria are found in the colon. This is the normal colon lining, and this is the colon lining of a person with clostridium difficile. So you can see a big change from the nice pink color to a kind of a disease-looking, where you can see the colonies of the bacteria on the mucosa lining.
The clinical usefulness of clostridium treatments can be virtually any neuropsychiatric disease, as well as other illnesses as well. So it’s a very important marker in the organic acid test. So it’s been useful in schizophrenia, psychosis, depression, chronic fatigue, Ticks and Tourette syndrome, autism, ADD and ADHD, OCD or obsessive-compulsive disorder, seizure disorders, gastrointestinal disorders, and it can be either diarrhea or constipation.
Some people don’t really think that clostridium is only associated with diarrhea, but that’s not true. It can also be associated with constipation. And also I’ve seen a number of cases in chronic fatigue syndrome.
So this can be an important factor in a wide range of different illnesses. I now want to turn to quinolinic acid, and it’s important. It also is a quinolinic acid is an important neurotransmitter, and it is one of the excitotoxic neurotransmitters.
When it’s present at a high concentration, it overexcites neurons to the point where they can become fatigued and die. But it’s very important because processes that cause inflammation increase the quinolinic acid. Quinolinic acid is derived from the amino acid tryptophan.
Tryptophan is very important because it’s converted to serotonin, and then serotonin is then converted to a metabolite 5-hydroxyindoleacetic acid, which is measured in the organic acid test. Some of the substances that increase this conversion are interferon, cytokine, or regulator of the immune system produced by the white cells that helps to kill viruses, but also by the cortisol, one of the main hormones of the adrenal gland, and also by immune overstimulation. So these substances increase the amount or activity of enzymes called indoleamine 2,3-dioxygenase or tryptophan 2,3-dioxygenase, and by a series of reactions they form quinolinic acid.
But this enzyme is one of the most important because this enzyme is regulated by the immune system. This is one of the reasons that I frequently recommend that people don’t use tryptophan as a supplement because tryptophan has the ability to be converted to quinolinic acid, and at high levels this can be extremely toxic and form a severe inflammatory reaction called the severe inflammatory reaction. I think I’ve got it on the next slide.
The quinolinic acid can be detoxified by combining with a sugar type of molecule, phosphoribosyl pyrophosphate, to form nicotinic acid mononucleotide, but if you’re exposed to phthalates and plastics, this interferes with this reaction and so you have excess of quinolinic acid. So this is why the substances called phthalates have probably been involved in so many toxic reactions and why they are toxic because of inhibiting this particular enzyme. So the inflammatory reaction is called eosinophilia myalgia syndrome.
So this is blowing up the first part of the reaction, so tryptophan can be used to form proteins or it can be converted to serotonin and then on to melatonin or to its metabolite in urine called 5-HIAA. The benefit to the body is that quinolinic acid kills bacteria, viruses, and parasites. So this is the kind of thing where you can’t say just automatically that quinolinic acid is bad because it helps our bodies to kill these invading microorganisms.
Quinolinic acid becomes harmful if these infections keep occurring for extended periods of time so the body keeps making quinolinic acid over and over and over again and there becomes so much quinolinic acid that it causes inflammation throughout the body. So it can cause lots of problems like the problems in chronic fatigue syndrome or arthritis and it’s also elevated in many of the neuropsychiatric diseases, multiple sclerosis and Alzheimer’s and Parkinson’s disease. So the quinolinic acid may be mediating damage that occurs to the muscles but as well as damage that occurs to the brain as well.
And one of the most interesting things is one of the major factors that increases quinolinic acid is a beta amyloid peptide that’s found to be very elevated in the brain of people with Alzheimer’s disease. So this is showing a network of healthy brain cells compared to brain cells in the patient with Alzheimer’s and here you see these are the deposits of this beta amyloid which is when pathologists analyze the brain of Alzheimer’s patients they find this protein in very high concentration in the brain. And it looks as if this substance is harmful because it stimulates the production of the enzyme that produces excess neuroinflammatory quinolinic acid which again is measured on the organic acid test and it’s found that the stimulus for production of this is bacteria in candida.
So when a person has infection the immune system produces large amounts of this substance in order to fight infection but again if the infection is too severe or it occurs for an extended time period it may cause damage. I remember reading that it’s common that people with Alzheimer’s disease commonly had repeated urinary tract infections before they got their illness and of course the urinary tract infections are commonly treated with antibiotics. The antibiotics cause candida overgrowth and then the elevated candida overgrowth causes the overproduction of this amyloid protein which then produces quinolinic acid that causes brain damage.
So the way in which infection, uncontrolled infection, can lead to brain damage that is really caused by the person’s own body system. Again, indications that quinolinic acid is a factor in Alzheimer’s disease and one of the ways that quinolinic acid causes its damage is that it causes lipid peroxidation. And so the breakdown of these lipids or fats in the brain is one of the things that is associated with Alzheimer’s.
So just showing a blowup of how these phthalates, which are involved with plastics, are causing problems. The phthalate, if you look here and compare it to quinolinic acid, has almost exactly the same structure. You see COOH, COOH here and here.
The only thing different in these molecules is that the quinolinic acid has a nitrogen here whereas phthalate doesn’t have a nitrogen. So because of the similarity, it’s able to inhibit this enzyme and prevent quinolinic acid from being removed and also prevent the body from making this key coenzyme called NAD. It’s also blocking this pathway as well.
It’s found that a wide number of infectious agents cause high amounts of quinolinic acid. So in this particular experiment, the monkeys were injected with poliovirus, and they looked at what happened to the different animals, what happened to the amount of quinolinic acid. So they found if the monkeys were completely paralyzed, that’s the bar in black, that represents this one, the amount of quinolinic acid went to gigantic values, whereas the animals that were just given a saline injection, they had no change in the quinolinic acid.
If they became a little bit weak from the poliovirus, the quinolinic acid went up a little bit more. If they had partial paralysis, it went up here. And if they had complete paralysis, the quinolinic acid went up to this level.
This is demonstrating that the quinolinic acid is the substance that is causing these severe effects. And on the other hand, the quinolinic acid is the substance that is the body is using it as an attempt to try to kill this virus, but in this case, unfortunately, the body has failed. So one of the substances that is regulated is the gamma interferon affects the amount of this enzyme that breaks down tryptophan to form quinolinic acid.
If you look at the amount of quinolinic acid in urine, these are from patients who have severe arthritis. There’s a direct relationship between the amount of quinolinic acid in urine and the degree of arthritis severity. So what this says is you can use quinolinic acid in urine to find, use the organic acid test to find out if this particular substance is elevated in urine.
If it is, then that indicates there’s excess conversion of tryptophan to quinolinic acid, and there’s a number of nutritional supplements that can be taken to reverse this particular problem. So using biochemistry, you can find exactly what one of the main causes of arthritis severity is. So some of the summary of the lessons about this pathway.
Only a small proportion of tryptophan is converted to serotonin. A lot of it would be converted to quinolinic acid, a potent oxidizing neurotoxic compound implicated as major cause of neurologic, psychiatric, and degenerative diseases, and it can also cause a very severe illness that was fatal a number of years ago, eosinophilia myalgia syndrome. You can look at the balance of the serotonin metabolite and quinolinic acid to see that the body’s production is in balance.
If it is in balance, that may be one of the causes of depression and even severe brain damage if the values are too high, like in Alzheimer’s. The imbalance may cause by excess gamma interferon, which may be caused by multiple vaccines at one time or by a virus infection, or it can be caused also by excess tryptophan or excess stress that causes high cortisol. So to treat this problem, if the person has an infection, you need to treat the infection, reduce the stress, and things like exercise, prayer, and meditation are very useful for that, and also eliminate phthalates.
So sauna treatment to get rid of phthalates could be helpful, and if the amount of serotonin metabolite is too low, you can use the supplement 5-HTP to treat this value. It’s very common and low in depression, but it’s also commonly low in autism as well. The organic acid test has the Krebs cycle metabolites.
Here you see all of the Krebs cycle metabolites, or most of them are elevated, which can be due either to a mitochondrial disorder. The Krebs cycle only takes place in the mitochondria, or it can be due sometimes to candida infection as well. The organic acid test has a number of markers for abnormalities in oxalate metabolism.
High oxalates are a very common problem in the American public. Perhaps 10% of individuals may develop problems with high oxalates in kidney stones during their lifetime, so they’re an extremely common abnormality, and the organic acid test has a nice marker in lactic acid. The high lactic acid can be due to either severe intestinal dysbiosis or to mitochondrial problems.
This is a mummy that was discovered in South America, and when the mummy was x-rayed, it was found it had a large golf ball-sized oxalate stone in the kidney, which undoubtedly was the cause of death. Oxalate stones can form all throughout the urinary tract, in the kidney itself, in the ureters, or in the bladder. All of these places can form these oxalate stones, which can be very painful.
Here you see a picture of the oxalate stone in the kidney that was removed following the removal of the kidney. Oxalate crystals can come in a variety of colors and can have very sharp edges, and one of the reasons that the kidney stones are very painful is because these crystals have these very sharp edges that are poking and prodding and cutting into the tissue surrounding them. So 10% to 15% of adults will be diagnosed with a kidney stone in their lifetime.
A million Americans have kidney stone each year. The vast majority of these kidney stones are due to oxalates. If you’ve ever had one before, your chance of getting another one is very high, unless you take the protective substances, supplements, and use a lower oxalate diet.
Typically there’s pain in the side and back below the ribs, pain lasting 20 to 60 minutes of different intensity. Oxalate crystals can form in every tissue. So here’s an example of these black crystals in the heart tissue.
So you can see these oxalate stones can actually tear the heart apart. As the heart contracts, it pushes into these sharp crystals and actually acts like little knives to tear into the heart tissue. And just recently it’s been found that these oxalate crystals may also be a cause of atherosclerosis.
They deposit in the arteries and also cause severe inflammation that eventually can lead to the blockage of the arteries. Other diseases in which oxalate may play a role, arthritis, joint pain, cystitis, vegetarianism. This can be for the person who’s a vegetarian.
People who are vegetarian are much more susceptible to having the problems with kidney stones as well as other oxalate-related illnesses because virtually all oxalates are found in plant matter, not in meat or fish. Osteoporosis can occur if the oxalates form in the bone. And another reason why vegetarians may have weaker bones is because of the high amounts of oxalates in their diet.
They can cause heart disease. It can make heavy metal toxicity worse and can also be a factor in thyroid disease. It’s very interesting that kids with autism have much higher values than normal children and the removal of oxalates from the diet has helped individuals with autism and with other severe neurologic disease has improved behavioral function by getting rid of these excess oxalates.
There’s a correlation between the candida marker and oxalates and a number of medical therapies to control oxalates indicate that antifungal therapy is one of the important treatments in helping individuals who have problems with excess oxalates. The organic acid test also tests for the fatty substances that are elevated in diabetes. These are called ketones and it’s because they have a smell like the fingernail polish removal because one of the substances, acetyl acetic acid, is actually broken down to form acetone.
So if there’s a chemical-like smell of the urine, it can be because of these excess fatty acid metabolites. In addition, the other fatty acid metabolites commonly indicate a deficiency of a key nutrient called carnitine. So ketosis, which means excess amounts of these ketones, can be caused by excessive fat breakdown and the two compounds are 3-hydroxybutyric and acetyl acetic acid.
And one of the most common things is juvenile diabetes called diabetes mellitus from the word, and I don’t remember if it’s Greek or Latin, for sweet. There can be fasting will cause these values to increase as well as worse starvation. They’re also elevated during illness.
In illness, you don’t want to eat much and so your body burns its fat, but it also can be due to genetic disease. And I’ve also seen that individuals have severe candida. The candida either prevents the body from absorbing enough carbohydrate or from utilizing it, and as a result, the person burns a lot of fat because the candida is impairing carbohydrate metabolism.
The nutritional markers for different vitamin deficiencies are also included here, and there’s one of the things I want to mention is that some of these markers, a high value indicates deficiency. So, for example, methylmalonic acid, this is an individual whose value is in the normal range. There’s no marker of high or low here, but if the value was high, it would indicate a deficiency.
I don’t have this here, but on the new test, there’s an asterisk to indicate so that if the substance is one of these inverse markers, there will be a high value indicates deficiency, and it’s a footnote down here. This version, unfortunately, doesn’t have it. So the current version does warn you that for some of these things, a high value indicates deficiency, whereas for some of the markers like vitamin B6, a high value would just indicate the person has loss.
So this is a person who is in the low end of normal, so is close to becoming deficient in vitamin B6.
So these are clearly marked in the new version so there’s no confusion. So a large number of the different vitamin deficiencies can be determined.
So this is one of the most comprehensive tests available for overall vitamin deficiency. The methylmalonic acid is one of these indirect markers, measures B12, methyl citric, measures biotin, glutaric and succinic indicators of riboflavin and coenzyme Q10 deficiency. In addition we have the direct markers vitamin C, panethylic acid and pyridoxic acid.
This is an example of vitamin C deficiency with the gums being unhealthy because of the deficiency of vitamin C. Vitamin C is needed for the production and maintenance of collagen, which is the connective tissue in bones, teeth, skin and tendons. It’s needed for wound healing. It’s needed for stress horn.
So if you’re under a lot of stress your vitamin C becomes depleted from your adrenal glands and you need additional vitamin C. Vitamin C is one of the most important antioxidants. A lot of women know the trick, and maybe some guys too, which is that if you put lemon juice on apple slices they don’t turn brown. It’s because the lemon has high amounts of vitamin C that prevent the oxidation of the the invisible pigments in the apple oxidizing and then forming the brown color.
Deficiency of vitamin C causes scurvy. It can cause a type of anemia in which there’s small red blood cells. Micro means small, cytic means cells.
So if the red blood cells are smaller than usual, it can be caused by vitamin C deficiency. There can be bleeding gums and loose teeth or wound healing. So any of you who are going to surgery or children who go to surgery, it’s always a good idea to take a few grams of vitamin C both before surgery and after surgery too, so that your surgery wounds will heal up a lot better.
Vitamin B12 is needed to remove methylmalonic acid, and so methylmalonic acid increases if B12 is low. The reasons are you don’t take much. Vitamin B12 is only found in animal products, so if you’re a strict vegetarian, at some point or another you may develop severe B12 deficiency.
If you are vegetarian, you need to make sure that you’re getting supplements of B12 from another source. And there are some individuals who have autoimmune disease, so they can’t absorb B12 right, or they may have celiac disease in which absorption of everything is poor, and there are certain genetic diseases where you can’t convert B12 to a certain needed coenzyme. The symptoms of B12 deficiency include a macrocytic anemia, which means large red blood cells.
Fatigue and weakness is a very, very common surgery problem. A sore mouth or tongue is also a common thing. It’s very important that elderly people who are depressed always get tested for possible B12 deficiency because depression, psychosis, and even dementia have been shown to be simply due to deficiency of vitamin B12.
And a number of studies have shown that people in the lower range of normal may also have impaired mental facilities, and so the recommendation is that anyone who is in the lower range of the normal range also be supplemented extensively for B12 deficiency. I think that the current thinking is if the value is less than 500, the patient should probably supplement with B12. This is the structure of B12.
This is the compound that’s called cyanocobalamin. There’s other types of B12. This is methylcobalamin that has been used in a lot of neurologic and psychiatric diseases as well as in autism, and there is another form of vitamin B12 coenzyme called deoxyadenosylcobalamin that has different biochemical functions.
I now want to turn to the vitamin biotin. I always think of biotin as an important substance when I see the Rocky movie. In the Rocky movie, Sylvester Stallone is running up and down the steps, I think it’s at the public library in Philadelphia, and afterwards he’s shown drinking while scoffing down all these raw eggs.
Well, the problem is raw eggs have a substance that will bind the biotin in food, and the person will develop a deficiency. So I was real curious if Stallone did that very long. Did he develop a biotin deficiency? So some of the biochemical facts about biotin, it’s necessary for gene stability, and it actually is involved in regulating the DNA.
It becomes attached to the histones, which are the proteins that regulate the translation of DNA into RNA, and so the biotin plays a role in turning off and turning on certain genes, and it’s also a coenzyme, which means it helps different enzymes, five different enzymes in the human body. Symptoms of biotin deficiency, hair loss, cleft palate is very common, and so a very high percentage, this is one of the most common vitamin deficiencies there are. It’s estimated perhaps 30% of pregnant women may be deficient in biotin, and it can cause fetal abnormalities if a mother is deficient during the pregnancy.
It can also cause skin rash, depression, fatigue, insomnia, hallucinations, muscle pain, and it can be due to excess raw eggs, antibiotic overuse. Antibiotics cause the problem because a lot of the gut bacteria produce biotin, and many people get their biotin from their gut flora, so when you take antibiotics, you lose that, and if you’re also eating any raw eggs, the raw eggs will make it even more severe, and just recently there was a patient who had all of these substances. She felt extremely fatigued.
She had muscle pain. She was depressed. She had fatigue and insomnia, and the organic acid test showed that she had biotin deficiency, so a great benefit of the organic acid test is that it can test for a wide range of different factors simultaneously.
A deficiency of an enzyme that recycles this vitamin biotin has been associated with autism, so this is the report. So this patient had a deficiency in the enzyme that recycles biotin, so in effect the biotin can only be used once, and then it’s no good if the person has this disease, whereas the normal person has an enzyme so that whatever biotin you have can be recycled, and they hypothesized that this caused biotin deficiency in the brain and caused the serious neurologic problems such as stereotyped and autistic behaviors. There was another case of a child with autistic symptoms, and the infant had progressive lethargy, which means tiredness.
The amount of hair is low. So if your child ever loses hair or if you lose hair, and it’s a general hair loss, so this doesn’t apply to men who have the typical male hair loss, but if you have general hair loss from the scalp in an unusual way, it can be due to biotin deficiency. And this particular child also had autistic behavior, had problems with seizures and repetitive startles, and by using high doses of biotin as a supplement, all of these symptoms were able to be cleared up.
So, again, a way in which organic acid testing quickly found out what the cause of an abnormality was that resulted in a very fast treatment for a patient who had all the symptoms of autism. This is the research group that found that the cleft palate in infants is related to the biotin deficiency of the mother. Biotin is also very useful for individuals who have diabetes for a long period of time, and sometimes develop nerve pain or peripheral neuropathy, and it was found by giving biotin in high doses for two years, the individuals had a completely reversed, a very severe neuropathy, and only within four to eight weeks there was an improvement in the clinical findings, and it’s suggesting that in some way biotin is helping one of the enzymes that may be deranged in diabetes.
This shows the baby with the cleft palate. So the marker that’s used to detect this is methyl citric acid. It is only produced, it’s only elevated in biotin deficiency, and as a result of biotin deficiency the propionyl-CoA reacts and reacts with a citric acid metabolite to form methyl citric acid.
Turning to another enzyme is pantothenic acid. It’s also considered one of the B vitamins. It’s a little bit confusing because pantothenic acid is part of a B vitamin called coenzyme A. Coenzyme A is completely different than vitamin A, which is a fat-soluble vitamin, but, again, it’s one of the essential vitamins that gets measured directly in the organic acid test.
The deficiency causes fatigue, weakness, burning feet, dermatitis, hair loss, loss of the pigment in the skin, and can lead to adrenal failure. Just getting back to the clostridia factors, summarizing this again. And one of the things is that the clostridia factor and the toxic factor from the acetaminophen can cause a deficiency of glutathione.
This marker, pyroglutamic acid, is a very good marker for deficiency of glutathione, and I’ve seen this in some of the cases where there was a high clostridia marker or the person had drug toxicity, this pyroglutamic acid would be extremely elevated. So it’s an excellent marker for glutathione deficiency. This is showing some of the other markers in the test.
The test includes marker for the RNA and DNA base called uracil and thymine. So thank you very much.
