Some people with autism may have metabolic disorders that can lead to severe reactions to an anti-cancer drug.
Some people with autism symptoms may lack certain proteins (enzymes) that are required by the body to use food as energy. These genetic deficiencies may also change the way their body uses medications. This study reported that people who have deficiencies in dihydropyrimidine dehydrogenase (DPD) may have severe reactions to an anti-cancer drug called 5-fluorouracil (5-FU). The authors also talked about other metabolic disorders and other medications in this article.
Autism Therapy: carnitine
definition of carnitine: Carnitine, sometimes referred to as L-carnitine, is found naturally in the body and is used to carry fatty acids into the mitochondria of the cell to make energy. Carnitine can be found in foods such as meat, fish, and milk. Carnitine can also be made in the body, but the body requires vitamin C in order to make carnitine. Carnitine supplements may also be purchased.
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- The Journal of Toxicological Sciences, by Ito, T., published in 2009, summarized Sep 25, 2009
- Alternative Therapies in Health and Medicine, by Morris, CR, and Agin MC, published in 2009, summarized Sep 4, 2009
Combined vitamin E and omega 3 therapy may help a type of verbal apraxia (speech problems) that may be caused by food allergies and nutritional problems, and could affect children with autism.
Children with verbal apraxia have trouble saying words and may have severe speech problems. Many scientists have thought that verbal apraxia is a brain disorder. This study suggests that verbal apraxia may be a result of nutritional problems. This study tested 187 children with verbal apraxia. Many of the children also had autism. All children took 400-3,000 International Units (IU) of vitamin E daily. They also took 1-3 grams of polyunsaturated fats (including omega 3 fatty acids) per day. Almost all of the families reported that the children who received vitamin E and omega 3 therapy had better speech, imitation, coordination, and eye contact. The authors also described blood test results for 26 of the children. They reported low carnitine levels, high anti-gluten antibodies, low vitamin D levels, fat absorption problems, and other results. The authors described how nutrition and metabolism might be different in some children with autism. The authors said that two major problems with this study were that they asked parents to give their own opinion of whether or not the children were getting better, and they did not use placebo controls. Even so, they said the results are very promising.
- Current Neurology and Neuroscience Reports, by Zecavati, N., and Spence SJ, published in 2009, summarized Apr 6, 2009
Future research may show that metabolic supplements such as carnitine, coenzyme Q, and/or vitamin B12 can help some children with autism.
This review article describes the role of energy use (metabolism) in autism. The authors describe how some metabolic disorders can give the symptoms of autism. There are no good studies that show how many children with autism have metabolic problems. The authors suggest that doctors look at each patient and decide whether or not to order metabolic tests. Some metabolic problems have simple treatments such as eating more cholesterol or taking biotin supplements.
- Current Medicinal Chemistry, by Blaylock, RL, and Strunecka A., published in 2009, summarized Mar 10, 2009
Vitamin B6, vitamin C, vitamin B12, magnesium, and omega-3 fatty acids may improve symptoms of autism.
Autism is a spectrum disease and research has shown that it is likely caused by many genes. This paper describes the idea that autism is caused by a problem with the glutamine chemical in the brain. The authors propose that if glutamine does not work well within the brain, then microglia cells in the brain may become active and secrete many factors that can harm the brain. These factors may then cause symptoms of autism in people who are at genetic risk for autism. Treatment approaches would include use of supplements and reduction of processed foods that have additives that contain glutamate and aspartate.
SPECIAL SUPPLEMENTS AND COMPOUNDS, WHICH ARE KNOWN TO REDUCE EXCITOTOXICITY:
Methylcobalamin (vitamin B12)
Pyridoxal-5 phosphate (vitamin B6)
Vitamin E (mixed tocopherols)
Vitamin C (buffered)
CoQ10
Acetyl-L-carnitine
Alpha-lipoic acid
Magnesium glycinate or lactate
Zinc
Flavonoids
SPECIAL SUPPLEMENTS AND COMPOUNDS, WHICH ARE KNOWN TO REDUCE MICROGLIAL ACTIVATION:
Ibupropen
Mincycline
Ferulic acid
DHEA
Curcumin
Quercetin
Silymarin
Baicalein
Resveratrol
DHA/EPA
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Please comment on carnitine or other autism therapy topics.
Synonyms for carnitine include: L-carnitine
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Nutrition and Essential Fatty Acids May Help Verbal Apraxia and Autism
Dec 2, 2009 by AnonymousCan nutrition help verbal skills in children with autism? A study reported the August 2009 issue of Alternative Therapies says yes, for some children. Combined vitamin E and omega 3 therapy may help a type of verbal apraxia (a type of speech problem) that may be linked to food allergies and nutritional problems.
Children with verbal apraxia have trouble pronouncing words and may have severe speech problems. Many scientists have thought that verbal apraxia is a brain disorder. This study suggests that verbal apraxia may also be related to metabolism differences and nutritional problems.
Metabolism is the process of making energy from food. Metabolism is a complex system of enzymes, proteins, fats, and carbohydrates that work together to digest food and turn it into energy that the body can use. People likely have a wide range of metabolic differences. Some of those differences can be quite large for some individuals. In this study, they suggest that some children with autism may have metabolism differences that affect how they process foods, and how their brain works.
What did the study show? This study tested 187 children with verbal apraxia, and many of them also had autism. All of the children took 400-3,000 International Units of vitamin E daily. They also took 1-3 grams of polyunsaturated fats (including omega 3 fatty acids) per day.
Almost all of the families (97%) reported improvements in speech, imitation, coordination, eye contact, and other skills with vitamin E and omega-3 therapy. There were few side effects reported during the length of the study.
The authors also described blood test results for nutritional information about 26 of the children. They reported low carnitine levels, high anti-gluten antibodies (suggesting a gluten allergy), low vitamin D levels, and fat absorption problems in most of the children they tested. They described how nutrition and metabolism might be different in some children with autism.
What do these results mean for children with verbal apraxia and autism? The results are exciting because 97% of the children showed improvements, and there were few side effects. Sounds perfect, doesn’t it? But it’s not quite as perfect as it sounds.
There are some major limitations of this study. First of all, the researchers asked parents to give their subjective opinion of improvements. The parents knew they were in a study. Although they were given specific improvements to look for, there is a possibility of bias in favor of reporting a good result.
Secondly, they did not use placebo controls. All of the parents and children knew they were getting the supplements. There is the possibility of the “placebo effect” which is when people taking placebo (“sugar pills”) report feeling better or actually show improvements. Many think it is the power of the mind/body connection that somehow influences how they feel or even how their body physically responds. There is scientific evidence for brain connections to the immune and endocrine systems to support these observations. It is possible that, in this study, the children and/or parents were hopeful that the supplements would work, and that influenced the outcome. There was a placebo effect observed in a recent study of citalopram and autism in children.
Third, the supplements may be helpful for only a subset of children with verbal apraxia. The researchers chose children with verbal apraxia who also had metabolism differences….
What is the bottom line for omega-3 and vitamin E from this study? In spite of the shortcomings of this study, the results are very promising. Children with verbal apraxia may benefit from vitamin E and omega-3 supplements, which may get their metabolism on a better track. And researchers will continue to explore the nutrition/metabolism link with brain function. Good nutrition is likely to be important for many brain functions, not just verbal apraxia.
Pure L-carnitine
Oct 21, 2008 by AnonymousWe are using carnitine for our adult son with autism and OCD and depression. It helps the depression a lot and seems to last about 5-6 hours. Might be worth a try.
Carnitine fumarate
Mar 23, 2007 by AnonymousMy son has Prader-Willi Syndrome and I know this is different from autism. I am posting this entry here, though, because his response to carnitine fumarate is really amazing. His OT was really impressed with how it has improved his processing speed. It works by improving fatty acid metabolism. Fatty acid metabolism is an area of active research for autism therapy. There doesn't really seem to be a downside to giving carnitine fumarate (other than diarrhea).
The text below is lifted from www.PWSNotes.org.
So, what is L-carnitine _fumarate_? Most L-carnitine sold by supplement manufacturers is either L-carnitine hydrochloride or L-carnitine _tartrate_ (L-carnitine bound to tartrate). With L-carnitine _fumarate_ (which was developed and patented by Sigma Tau, the maker of Carnitor), the carnitine is bound to fumarate, which is a key substrate in what is called the Kreb's cycle in mitochondria for the production of energy. It is the Kreb's cycle that produces the electrons that are then passed along respiratory transport chain complexes 1-IV for the production of ATP (the basic cellular form of energy). Citrate synthase is the key enzyme involved in the first step of the Kreb's cycle and as such can be rate-limiting for the whole cycle. Fumarate, though, is the substrate for the next to last step in the Krebs cycle and its related enzyme is fumarase.
About 58% of L-carnitine fumarate is L-carnitine, with the rest being fumarate. After it is ingested, the body separates the L-carnitine from the fumarate. Although I can't say for sure at this point, what might be happening is that the L-carnitine part is going off and doing all of the good things it is known for in terms of transporting fatty acids into the mitochondria for burning for energy and whatnot, while the fumarate is entering the Kreb's cycle and boosting its output of electrons that are then transferred to the electron transport chain, resulting in an increase in the production of cellular energy in the form of ATP. If that's what is happening, it could be the extra fumarate is providing a pathway around a metabolic block, possibly in succinate dehydrogenase (SDH), given that SDH is the enzyme that catalyzes the succinate-to-fumarate reaction. If so, it could be that the impairment in respiratory chain transport is not a primary event but is instead a downstream result of reduced substrate availability in the Kreb's cycle. (Interestingly, fumarase deficiency is a very rare autosomal recessive disorder in which the metabolizing of fumarate in the Kreb's cycle is sharply reduced or completely absent and is characterized by massive secretion of fumarate in the urine, encephalopathy, hypotonia and severe developmental delays, all of which (aside from excessive fumarate secretion) are rather reminiscent of another syndrome that we are all too familiar with.)
The Pure Caps capsules contain 586 mg of L-carnitine fumarate, with 340 mg of that being L-carnitine and 246 mg being fumarate. Sulli is only getting 1/4 capsule a day, which works out to about 85 mg of L-carnitine and 60 mg of fumarate for a 16 lb (7.25 kg) baby, which is about 12 mg/kg/day of L-carnitine and 8 mg/kg/day of fumarate. That's a surprisingly small amount of L-carnitine to be providing such dramatic benefit, given that the recommended dosage range for Carnitor is 35-50 mg/kg/day, and provides further support for the hypothesis that the fumarate part could be providing a significant amount of the benefit.
I've spent some time looking into the safety of L-carnitine fumarate and fumarate. L-carnitine fumarate is a relatively new form of carnitine and there aren't many clinical studies involving its use. The studies I found all have to do with Sigma Tau's patented formula for male infertility, ProXeed (yes, among other things, carnitine helps sperm swim better :-). The daily dose of that formula contains 2 g/day of L-carnitine fumarate, 1 g/day of acetyl-l-carnitine, 4 g/day of fructose and an unspecified amount of citric acid (which is also a metabolite in the Kreb's cycle), and in clinical trials seems to have been very well tolerated aside from the usual occasional side effects of large doses of carnitine (i.e., transient nausea and digestive upset, loose stools, etc.).
I have not been able to find any reports of fumarate being used as a supplement. However, fumarate is a component of ferrous fumarate (used globally for iron deficiency anemia in children and adults), as well as a number of drugs, including quetiapine and retroviral inhibitors such as tenofovir. In general it seems to be a safe substance (although it probably shouldn't be used by those with fumarase deficiency).
So what's the bottom line here? It could be that the L-carnitine vs. acetyl-l-carnitine question will become moot and the L-carnitine fumarate form could become the carnitine of choice for those with PWS.
For those who are interested in trying L-carnitine fumarate, the Pure Caps page for it is at http://www.purecaps.com/itemdy00.asp?T1=LCF1, with supplementary information at http://www.purecaps.com/PDF/pi/l_Carnitine_Fumarate.pdf. Jarrow also has (http://www.jarrow.com/product.php?prodid=191), as does Doctor's Best (http://www.drbvitamins.com/nutritionalproducts_details.asp?id=16). Make sure the label specifies that the L-carnitine is the fumarate form and not the more commonly available L-carnitine tartrate. All of the L-carnitine fumarate on the market is made by Sigma Tau and is pharmaceutical grade.
Please note that I am in the process of revising the carnitine and Coenzyme Q10 articles to suggest that, especially for older children, carnitine and/or CoQ10 supplementation be started with very low doses and then very slowly increased in order to give the child (and their parents) plenty of time to adapt to more normal levels of mental and physical energy. After all, older children with PWS have lived with a significant mental and physical energy deficit for years and to them that is "normal." Then CoQ10 or carnitine is started, and all of a sudden the world is a brighter, busier place, they're experiencing all kinds of new perceptions and sensations, and their thinking is zipping along at a significantly faster pace. It's probably much like going from a dim room out into bright sunlight, except way more intense because the increase in energy they're experiencing is a full body and mind experience. So it's not surprising that it could be a somewhat disorienting experience that could lead to emotional, mental and physical reactions that others interpret as irritability. I therefore consider it important that the increase in mental and physical energy provided by CoQ10 and/or carnitine be increased very slowly so as to give the child and their parents plenty of time to adapt, physically, mentally and emotionally, to each step up to a higher level of energy as the dose is slowly increased. It will also probably be helpful if the parents talk with the child ahead of time about what kinds of things they might experience when the CoQ10 or carnitine.
I think the need to proceed very slowly is somewhat less of an issue for infants and toddlers, especially those who are badly delayed in such things as babbling and talking, head control, sitting, and walking, as they have not spent nearly as much time entrained by a significant energy deficit and I think it is important to get them developmentally on track as soon as possible. But as always, it is critical that parents use their intimate knowledge of their child and intuition in determining the approach that will be best for their child.
I also need to note that there is the possibility that the irritability reported in some of those with PWS when CoQ10 supplementation is started could be due to the increased energy unmasking an intrinsic behavioral disturbance that was previously "sedated" by a serious impairment in cellular energy availability. At this point I have no way of determining how much of that irritability could be the result of a some level of understandable disorientation due to a sudden increase in mental and physical energy (as described above) or is due to an unmasking effect. If it does turn out that CoQ10, carnitine, or anything else that improves energy metabolism and mitochondrial function in PWS to more normal levels can unmask a previously sedated behavioral disturbance, I think there are ways that could be dealt with, but that is beyond the scope of this post. I will note once again, though, that my hunch is that at least some of the severe behavioral problems associated with PWS are due to (1) chronic intermittent hypoxia and sleep fragmentation caused by under- or untreated breathing disorders, and/or (2) untreated energy metabolism problems that lead to repeated episodes of hypoglycemia, which is well-known to cause severe irritability and anxiety as well as psychotic-like symptoms and out-of-control rages. I therefore consider it essential that any breathing disorder be aggressively treated and every effort made to ensure stable blood sugar levels throughout the day.