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Tuesday, May 31, 2011

Acetyl -L Carnitine (ALC)

What is it?

 Acetyl-L Carnitine is an amino acid that occurs naturally in the body and is also found in milk and red meat, in particular mutton (older, mature sheep). 

 It is involved in the transport of fats to the mitochondria (energy producing cell structures of the cells). It also protects nerves from stress and heals damaged nerves caused by injury. In January 2002 a team of researchers showed that Acetyl -L Carnitine combined with Alpha Lipoic Acid, a fatty acid, could delay the ageing process by increasing energy (see below). Acetyl -L Carnitine was found to nourish brain cells, protect from free radicals and stress, increase blood flow, reduce depression, improve cognitive abilities and increase memory in the elderly. (We can consider that what is good for those who are aging, are also good for those with DS because they have accelerated aging.) It is indicated in the treatment of Alzheimer, AIDS, depression, fibromyalgia, heart disease, memory loss, multiple sclerosis and stress.
Acetylcarnitine and carnitine play important roles in the human body. These nutrients shuttle acetyl groups and fatty acids into mitochondria for energy production. Without carnitine, fatty acids cannot easily enter into mitochondria. The acetyl group is used to form acetyl-CoA, the most important intermediary in the generation of energy from amino acids, fats, and carbohydrates. Therefore it serves as an energy reservoir of acetyl groups and both nutrients help improve energy production. The acetyl group is also used to make the important brain chemical acetylcholine. Some studies suggest that perhaps acetyl l-carnitine can even act as a neurotransmitter itself. This nutrient is sometimes abbreviated as ALC or ALCAR.
Acetyl-L-carnitine, also known as ALCAR, is a well-researched nutritional supplement. It is synthesized to provide a more bioavailable form of L-carnitine, which is a derivative of the amino acid lysine. L-carnitine is made naturally in the body by the liver and kidneys, and then transported to other tissues such as the brain and heart. Like L-carnitine, acetyl-L-carnitine functions as an antioxidant and promotes the production of glutathione, a free radical scavenger, in cells.


Overview of benefits for those with Down syndrome
(See below for details on each.)
ADHD  In a study done by Dr. Giovanni Neri from Universita Cattolica in Rome, he saw that with ACL, there was a more effective reduction of hyperactivity and improvement of social behavior. 
Alzheimer's disease May be helpful in those with Alzheimer's disease since it protects against amyloid-beta neurotoxicity 
Anti-aging and longevity with alpha lipoic acid Scientists at the University of California, Berkeley, CA rejuvenated aging rats by giving them a combination of alpha lipoic acid and acetylcarnitine. 
Memory Studies in aging rats shows acetyl-l-carnitine increases cholinergic synaptic transmission and consequently enhances learning capacity. The memory of aging rats is rejuvenated by giving them a combination of acetylcarnitine and lipoic acid. 
Improved Visual Functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica. 2005. 
Why is it necessary?

 Because L-carnitine is involved in cellular metabolism, acetyl-L-carnitine can help increase energy production in the mitochondria, the "power plants" of all cells, and thereby may generally boost physical and mental energy. As a dietary supplement, acetyl-L-carnitine is often used to help improve memory, and has been studied as a possible adjunct treatment for Alzheimer's disease. Acetyl-L-carnitine may also help address symptoms of depression, and may be useful in the treatment of Parkinson's disease, stroke, and Peyronie's disease. In addition, daily supplementation with acetyl-L-carnitine may have a protective effect on the central nervous system and may benefit the heart. There is also some evidence that acetyl-L-carnitine can enhance visual memory and attention in people with Down Syndrome (see below), and clinical data indicates that it also may slow age-related mental decline that is not associated with Alzheimer's.

 For products I use for Jett, see the DS Day to Day Store

 I give Jett (began when he weighed about 22 lbs, now he's at 26.4 lbs) two servings of about 500 mg each serving w/food. Once in am and once in the afternoon. I see that this dose is high. I haven't seen any hyperactivity, though. He still takes his nap fine and falls asleep at night.

Why Acetyl-L-Carnitine for the Down Syndrome population?

Clin Ter. 1994 Feb;144(2):123-7.

[Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome].

[Article in Italian]
De Falco FA, D'Angelo E, Grimaldi G, Scafuro F, Sachez F, Caruso G.

Source

Cattedra di Neurofisiopatologia, II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli.

Abstract

Neuropsychologic tests were performed in subjects with Down syndrome in order to assess the effect of a 90-day treatment with L-acetyl-carnitine (LAC). Findings were evaluated statistically (Wilcoxon test) and compared to three further groups of subjects: untreated Down syndrome, mental deficiency due to other cases treated and not treated with LAC (Mann-Whitney U-test). Treated Down syndrome patients showed statistically significant improvements of visual memory and attention both in absolute terms and in comparison with the other groups. No improvement was found in mentally deficient non-Down subjects, so that the favourable effect of LAC appears to be specific for Down patients. In view of the analogies of the pathology and neurochemistry between Down syndrome and Alzheimer degenerative deficiency (deficit of cholinergic transmission) it is suggested that the action of LAC in these pathologies is related to its direct and indirect cholinomimetic effect.
Dosage and frequency of use


 The typical daily dosage for long term use is 100 to 300 mg once a day, preferably in the early part of the day.  Higher amounts, such as 500 to 1000 mg, can be taken for short periods. Most people begin to notice the effect from after an hour or two, and the mental enhancement can last a few hours or all day depending on the dosage. There are many different dosages available over the counter ranging from 100 mg to 500 mg or more. 
Dr. Weil recommends 500 to 1,500 mg per day for an adult.

I give Jett (weighs about 22 lbs) two servings of about 500 mg each serving w/food. Once in am and once in the afternoon. I see that this dose is high. I haven't seen any hyperactivity, though. He still takes his nap fine and falls asleep at night.

 Dosing Notes

 Acetyl-L-carnitine is a powerful anti-aging nutrient that is beneficial for mild mental impairment; practitioners recommend 1,000 to 2,000 mg a day for up to ninety days.

Power Aging by Gary Null, page 192 

Results of this double-blind, placebo-controlled study found that treatment with 2 g of acetyl-L-carnitine per day for 24 weeks had beneficial short-term memory effects on patients with Alzheimer-type dementia.
The Clinician's Handbook of Natural Healing by Gary Null PhD, page 711
Several major studies have shown that daily supplementation with ALC significantly slows the progression of Alzheimer's disease, resulting in less deterioration in memory, attention and language, and spatial abilities.
Prescription for Nutritional Healing by Phyllis a Balch CNC and James F Balch MD, page 46
Results of this double-blind, placebo-controlled study showed that the administration of 2g per day of acetyl-L-carnitine for three months led to significant improvements in elderly patients suffering from mental impairment.
The Clinician's Handbook of Natural Healing by Gary Null PhD, page 854
Elderly patients receiving acetyl-L-carnitine at doses of 1,000 to 2,000 mg a day for up to ninety days found relief from mild mental impairments such as slow memory.
Power Aging by Gary Null, page 93
Results of this double-blind, placebo-controlled study indicated that the
administration of 1500 mg per day of acetyl-L-carnitine to elderly patients with mild mental impairments proved to be beneficial against cognitive and emotional-affective mental impairment. The Clinician's Handbook of Natural Healing by Gary Null PhD, page 706


Side effects
ALC is believed to be safe and is available without prescription at health food stores. Side effects of overstimulation, restlessness, and nausea may occur at dosages greater than 500 mg. Even higher doses may cause insomnia. If you happen to feel nausea, next time just take the acetyl l-carnitine with food or take a lesser dose. A few people may notice mild headaches.
Side effects can include mild gastrointestinal symptoms, such as nausea, vomiting, and abdominal cramps, as well as headache; an increase in agitation or restlessness; and an increase in seizure frequency in persons with seizure disorder. Persons with Alzheimer's disease may exhibit psychiatric disturbances, such as depression and confusion, but it is uncertain whether these effects are due to acetyl-L-carnitine or the disease itself. Some evidence suggests acetyl-L-carnitine may interfere with thyroid metabolism, so watch for symptoms. I haven't seen issues worsen on ACL in Jett.

Can Cognitive Deterioration Associated with Down Syndrome be Reduced?
By R. Thiel, Ph.D., Naturopath and S.W. Fowkes, B.A.

At least in eyes, it appears that acetyl-L-carnitine may have antiglycation abilities (55). Hendlor and Rorvik report, “”Acetyl-L-carnitine has recently demonstrated some efficacy as a possible neuroprotective agent for strokes, Alzheimer’s disease, Down’s syndrome and for the management of various neuropathies…recent studies show beneficial effects in Alzheimer’s disease. Younger patients seem to benefit most” (55). However, some few with seizure disorders have reported increases in seizure frequency or severity on acetyl-L-carnitine (54). As the DS population is much more inclined towards seizure disorders than the general public (56), caution would seem to be advisable regarding using acetyl-L-carnitine to attempt to prevent glycation. 
54. Hendlor SS, Rorvik D, eds. PDR for Nutritional Supplements. Medical Economics. Montvale (NJ) 2001
55. Swamy-Mruthinti S, Carter AL. Acetyl- L -carnitine decreases glycation of lens proteins: in vitro studies. Exp Eye Res. 1999;69(1):109-115
56. Thiel R, Fowkes SW. Down syndrome and epilepsy: A nutritional connection? Med Hypo. 2004; 62(1):35-44 

Research
- Ageing: - Liu J, Head E, Gharib AM, Yuan W. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A 2002 Feb 19;99(4):2356- "These results suggest that feeding ALCAR .. (acetyl-l-carnitine) ..and LA (R-alpha-lipoic acid) to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function."
- Hagen TM, Liu J, Lykkesfeldt J, Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A 2002 Feb 19;99(4):1870-5 "Feeding ALCAR in combination with LA increased metabolism and lowered oxidative stress more than either compound alone."
- Ando S, Tadenuma T, Tanaka Y, Fukui F Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res 2001 Oct 15;66(2):266-71
- Sorbi S, Forleo P, Fani C, Piacentini S. Double-blind, crossover, placebo-controlled clinical trial with L-acetylcarnitine in patients with degenerative cerebellar ataxia. Clin Neuropharmacol 2000 Mar-Apr;23(2):114-8 "After the trial, we observed a statistically significant improvement of some symptoms and a slow progression of the disease in both groups of patients."
- Acetyl-L-carnitine. Altern Med Rev 1999 Dec;4(6):438-41 " Studies have shown that ALC may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, diabetic neuropathies, ischemia and reperfusion of the brain, and cognitive impairment of alcoholism."
Benefit Details

ADHD benefit

L-acetylcarnitine may help with attention deficit hyperactivity disorder in children with the genetic disorder known as fragile X syndrome which results from an inherited genetic defect on the X chromosome. It is associated with  mental retardation and may also cause autism and ADHD, Dr. Giovanni Neri from Universita Cattolica in Rome studied boys between 6 and 13 years old for a period one year. Twenty four received l-acetylcarnitine and 27 received placebo. There was a more effective reduction of hyperactivity and improvement of social behavior. American Journal of Medical Genetics 2008.

 Alzheimer's disease


 May be helpful in those with Alzheimer's disease since It protects against amyloid-beta neurotoxicity.

Effects of acetylcarnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors.
Curr Med Res Opin. 2003.
An evaluatation was made of the effect of 2 grams /day orally for 3 months in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of acetylcarnitine.

 Anti-aging and longevity with alpha lipoic acid

Scientists at the University of California, Berkeley, CA rejuvenated aging rats by giving them a combination of alpha lipoic acid and acetylcarnitine. Lead researcher Dr Bruce Ames, said the results were astonishing: "With the two supplements together, these old rats got up and did the Macarena. The brain looks better, they are full of energy - everything we looked at looks more like a young animal." The animals' memories were also significantly  improved. The two chemicals in combination have a positive impact on  mini-organs within the body's cells called mitochondria and were able to mop up free radicals. Mitochondria generate energy within the cells and  their deterioration  is an important cause of aging.
   It is difficult to predict whether this combination is effective in humans, and if so, how to determine the ideal dose combination. In the meantime, those who wish to supplement prudently with small amounts may consider taking  about 5 to 10 mg of lipoic acid, and 30 to 100 mg of acetyl-l-carnitine. Since these nutrients are not often available over the counter in these small doses, you may need to open the capsules and take a portion. 

 Chronic fatigue syndrome

Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome.
Psychosom Med. 2004.
We compared 2 grams a day acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 chronic fatigue syndrome patients during 24 weeks. Acetylcarnitine significantly improved mental fatigue and propionylcarnitine improved general fatigue.

 Depression and low mood

ALCAR may benefit geriatric patients with mild depression.

 Diabetic neuropathy

Acetyl-L-carnitine in the treatment of diabetic neuropathy. A long-term, randomized, double-blind, placebo-controlled study.
Drugs R D. 2002.
A group of 333 patients with diabetic neuropathy were enrolled. Acetylcarnitine (or placebo) was given orally at a dosage of 2000 mg/day. This natural medicine was effective and well tolerated in improving neurophysiological parameters and in reducing pain over a 1-year period.
Acetyl L Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Patients With Chronic Diabetic Neuropathy: An analysis of two randomized placebo-controlled trials.
Diabetes Care. 2005.
We evaluated frozen databases from two 52-week randomized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine : 500 and 1,000 mg/day three times a day. Data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg.

 Hypertension and insulin resistance

Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy.
Hypertension. 2009.
We prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate in nondiabetic subjects at increased cardiovascular risk. It safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia.

 Memory

Studies in aging rats shows chronic administration of acetyl-l-carnitine increases cholinergic synaptic transmission and consequently enhances learning capacity. The memory of aging rats is rejuvenated by giving them a combination of acetylcarnitine and lipoic acid.

 Neuropathy

A pilot study on the effect of acetylcarnitine in paclitaxel- and cisplatin-induced peripheral neuropathy.
Tumori. 2005.
Twenty-seven patients with paclitaxel and/or cisplatin-induced neuropathy received at least one cisplatin or one paclitaxel based regimen, or a combination of both. Patients with chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1 g/die i.v. infusion over 1-2 hours for at least 10 days and it seemed to be an effective and well-tolerated agent for the treatment of chemotherapy-induced peripheral neuropathy.

 Peyronie's disease

ALCAR is more effective than tamoxifen in the therapy of acute and early chronic Peyronie's disease.

 Vision research study

Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10.
Ophthalmologica. 2005.
The aim of this randomized, double-blind, placebo-controlled clinical trial was to determine the efficacy of a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10 (Phototrop) on the visual functions and fundus alterations in early age-related macular degeneration. Findings suggest that an appropriate combination of compounds which affect mitochondrial lipid metabolism, may improve and subsequently stabilize visual functions, and it may also improve fundus alterations in patients affected by early age-related macular degeneration.

 Weight loss

Some people notice ALC reduces appetite but I have not seen formal studies using this supplement as an effective weight loss pill.

 What you may notice after taking a supplementThose who take carnitine pills notice an increase in physical energy, but not as much mental energy. Acetyl l-carnitine has a more immediate and noticeable mental effect than carnitine because it crosses into the brain much better and quicker. The mind boosting effect of ALC is often noticed within a few hours, or even within an hour. Most people report feeling mentally sharper, having more mental stamina, having more focus and being more alert. Some find a mild mood enhancement. 

Sources


Related Posts

The Amazing Goji Berry
The Importance of Magnesium
Piracetam
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Constipation: Causes and Cures
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Why B12 & Folinic Acid for Down syndrome?


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Piracetam

Piracetam is said to promote the flow of information (or messages) between the right and left hemisphere of the brain. Dean and Morgenthaler claim that it can enhance memory, language and learning abilities. It may also prevent memory loss and learning difficulties caused by trauma. By its action on the brain membranes it is also thought to prevent seizures. Finally it may be used for the treatment of myoclonus (uncontrolled muscle twitching or jerking) and for the treatment of Dyslexia.

For more information, please go to http://www.riverbendds.org/index.htm, click the Medical Series folder on the left hand side, then Supplements & Drugs, and then Piracetam.

Research:
- Epilepsy: Koskiniemi M, Van Vleymen B, Hakamies L, Lamusuo S, Taalas J. Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo. J Neurol Neurosurg Psychiatry 1998 Mar;64(3):344-348.

- Aphasia: Kessler J, Thiel A, Karbe H, Heiss WD. Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients. Stroke 2000 Sep;31(9):2112-2116

- Dyslexia: - Wilsher CR, Bennett D, Chase CH et al. Piracetam and dyslexia: effects on reading tests. J Clin Psychopharmacol 1987 Aug;7(4):230-237. "Piracetam-treated children showed significant improvements in reading ability (Gray Oral Reading Test) and reading comprehension (Gilmore Oral Reading Test)."

Source

http://www.henryspink.org/smart_drugs.htm

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Sunday, May 29, 2011

Folic Acid Cut Alzheimer’s Risk in Half

September 7, 2005 by Jean Carper

If you want to keep your mind sharp and avoid Alzheimer’s as you get older, don’t forget to take your folic acid daily. It can slash your chances of Alzheimer’s in half, says new research.
Getting 400 micrograms or more of folic acid a day cuts your risk of developing Alzheimer’s an astonishing 55 %, according to a large new study from the Institute for Brain Aging and Dementia at the University of California at Irvine.
Folic acid appears more powerful than antioxidants, such as vitamin E, and other B vitamins in slowing brain aging, say researchers Maria Corrada and Dr. Claudia Kawas who studied the impact of several dietary factors on the risk of Alzheimer’s among 579 people age 60 and older who participated in the Baltimore Longitudinal Study of Aging.
Those who got high vitamin E and vitamin B6 also had lower rates of Alzheimer’s. But only folic acid was associated with a significantly decreased risk.
Corrado, an assistant professor of neurology, noted that most people who got the amounts of folic acid needed to cut Alzheimer’s risk dramatically took folic acid supplements. The dose in food alone was not enough.
A recent Dutch study also found that older people who took 800 mcg of folic acid daily slowed brain aging by 5 years, compared with those on a placebo, as measured by scores on memory tests. For example, someone age 60 who took 800 mcg of folic acid daily had the memory of someone age 55.
Folic acid also helped prevent toxic deposits of beta amyloid, a marker for Alzheimer’s, in the brains of lab animals in tests at the National Institute on Aging. One theory is that high homocysteine due to a lack of folic acid (and other B vitamins) may damage the DNA of brain cells, promoting beta amyloid accumulation, leading to cognitive decline and Alzheimer’s.
Source: Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, August, 2005)

To save your brain from decline as you age, be sure to get B vitamins, particularly folic acid.
That’s the message from two major new studies finding that older people with diets and blood levels low in B vitamins are more apt to suffer cognitive decline, dementia and Alzheimer’s disease. Such individuals are also more apt to have higher blood levels of homocysteine, a protein tied to heart disease and dementia. .
Of all B vitamins, folic acid is most potent in protecting the brain from the ravages of aging–such as memory loss, dementia and Alzheimer’s–according to the new studies–one from Tufts University and the other from the University of Bologna in Italy. Both have just been published in the September issue of The American Journal of Clinical Nutrition.
Italian researchers found that older men and women with low folate (folic acid) blood levels were nearly twice as apt to develop dementia and Alzheimer’s over a four-year period as those with higher blood folate.
Subjects with the least folic acid in their diets and blood also performed worst on a number of tests of memory and cognitive function in the Tufts study. Those low in B6 also scored poorly on the cognitive tests.
What’s the reason? Scientists have long speculated that B vitamins, mainly folic acid, protect the brain by reducing toxic levels of homocysteine in the blood. Some believe homocysteine directly damages brain cells and function.
However, for the first time, these two new studies say that folic acid has powers to protect the brain independently, regardless of its ability to suppress homocysteine levels.
Bottom line: Both low intake of folic acid and/ or high blood homocysteine, predict brain decline as you age.
---
Folinic vs. Folic Acid

http://www.tahomaclinic.com/folate.html

June 2010 Nutrition & Healing

Is the mainstream still cheating you out of the best health possible—with folic acid?!

Discover the stunning truth behind this essential “vitamin”—and the simple switch that’s much, much better for you

Do you remember a few years ago, when “mainstream” print and broadcast media were telling us that vitamin E was bad for our cardiovascular systems, and would increase our risk of heart attack? Turns out the whole thing was based on -you guessed it- researchers not copying Nature!

They weren’t using Nature’s own of vitamin E—a combination of alpha-, beta-, delta- and gamma-tocopherol, sometimes with alpha-, beta-, delta-, and gamma-tocotrienol—in the same percentages and combinations found in Nature. Instead, they had used alpha-tocopherol only in their research—and reported an increase in cardiovascular risk.

Fortunately, since then it has been pointed out that gamma-tocopherol is more important in protecting the heart than alpha-tocopherol. In fact, supplementing alpha-tocopherol alone depresses levels of gamma-tocopherol, so increased risk to the heart isn’t altogether surprising. What can we learn from this? It’s pretty obvious—using a natural substance in a way that goes against Nature’s perfect design can cause problems.

Given the news, responsible vitamin suppliers quickly replaced alpha-tocopherol-only forms of vitamin E with “mixed tocopherols,” combinations of alpha-, beta-, delta, and gamma-tocopherols.

In a similar turn of events, recently accumulating research has found that supplemental folic acid, incorrectly identified as a vitamin (it’s actually an oxidized vitamin) since its synthetic crystallization in the 1940s, may actually accelerate cognitive decline in some older individuals. It’s also being linked to increased risk of colon and rectal cancers, increased risk of childhood asthma born to folic-acid supplemented mothers, and accelerated growth of pre-existing cancers.

There’s enough research that Reader’s Digest magazine recently published an article warning readers about the dangers of too much folic acid. Unfortunately, the article showed that not only journalists, but even medical professionals still haven’t figured out that folic acid is not the same as the naturally occurring vitamin folate.

Six of one is NOT half a dozen of the other

According to the article, a university-affiliated medical doctor stated: “We’ve known for years that getting too little folate can promote cancer. Now it looks like getting too much folic acid could be harmful too.”

Like much of the medical mainstream, he used folic acid and folate as interchangeable terms.

But folic acid is not the same as folate!

Folic acid is a single type of molecule, crystallized in 1943 by a scientist working for the patent medicine company Lederle Laboratories, then a subsidiary of American Cyanamid Corporation. Folic acid is the fully oxidized form of naturally occurring folates, which are found in leafy and green vegetables such as spinach, asparagus, turnip greens, romaine, lettuce, broccoli, Brussels sprouts, and bok choy. Other sources include corn, beets, tomatoes, dried or fresh beans and peas, fortified sunflower seeds and some fruits, including oranges, grapefruit, pineapple, cantaloupe, honeydew melon, banana, raspberries, and strawberries. Liver (only organic, of course) and brewer’s and baker’s yeasts are good sources of folate, too.

But—and this is important to understanding the difference between folic acid and the various naturally occuring folates—none of these vegetables, fruits, liver or yeast naturally contain even one molecule of folic acid.

How the mainstream convinced us we need folic acid, and not folate

So why is folic acid so firmly entrenched in the public and mainstream professional mind as a vitamin? For the same reasons that mainstream professionals, science writers (who should know better), and the majority of the public think that horse estrogen and human estrogen are the same thing. It’s a combination of a sloppy understanding of biochemistry and some clever patent-medicine-company-
supported and -promoted psychology.

First, the biochemistry. (Stay with me, it’s relatively easy.) Folate was originally isolated from brewer’s yeast and spinach in the 1930s. Once isolated and exposed to air it becomes unstable and breaks down, and is generally no longer useful in nutrition. But a small amount of natural folate can be transformed by oxidation (a natural process) into folic acid, a much more stable form with a very long shelf life.

While human and animal cells cannot use the folic acid molecule itself in their normal metabolic processes, human cells (principally the liver) can transform folic acid back into many of its metabolically useful folate forms. That’s why folic acid—despite not being found in food—can do so much nutritional good, the best-known example being the prevention of birth defects including spina bifida, cleft lip, and cleft palate.

As we grow older, though, our bodies are increasingly slow at transforming folic acid into usefully metabolized folates. That’s probably why scientists are finding that folic acid (not folate) is associated with cognitive decline in the elderly. Some of these studies have shown significantly elevated levels of un-metabolized (and therefore not useful) folic acid building up in the bloodstreams of supplemented older individuals.

In addition to worsening folic acid metabolism with age, there are also a significant number (as high as 5 percent or more in some populations) of survivable human genetic defects of folate metabolism which make it more difficult or, in some circumstances, impossible for sufferers to make metabolic use of folic acid.

Now, the psychology. Imagine you’re the sales and marketing arm of a patent medicine company. Which would you rather produce and sell: A then-process-patentable substance (folic acid) or an un-patentable substance (folate)? A substance with a longer shelf life (folic acid), or a substance that breaks down very rapidly on exposure to heat, cold, or light—even from “just sitting there” (folate)? A substance that’s less expensive to manufacture and process (folic acid), or a more expensive substance (folate)? The answer is pretty obvious—from a marketing point of view, folic acid wins every time.

And in this case, by great good luck, folic acid does do some good. It can be re-metabolized into various metabolically useful forms in most people—particularly younger people. So of course folic acid is promoted as a vitamin—even though it’s not found naturally in food—and manufacturers happily encourage everyone to speak of it interchangeably with folate, just as the Wyeth company so successfully confused Premarin with human estrogen in the public mind.

As usual, the mainstream way does more harm than the natural way

So since the 1940s, when physicians wanted to give their patients supplemental folate, they were taught to start with folic acid under one or another brand name. Even I was taught that at the University of Michigan in the 1960s. Supplement companies have sold folic acid, too, as it appeared to do the job, and there were for years no reports of harm. In fact there was very little, if any, research into potential harm.

But now that there is enough evidence of potential harm from folic acid, it’s time for all of us who want the benefits to switch back to the forms of folate found in food, which our bodies can use more efficiently and effectively than folic acid. Of course, we should always start by eating as much folate-containing food as possible, and as fresh as possible, too.

Remember, naturally occurring folates break down quite rapidly with heat, cold, light, even when they’re still in the food. Because of this naturally rapid breakdown, even the most avid vegetable and fruit eaters often need folate supplementation. (For a simple way to find out if you’re among them, see “Overlooked blood test could be the key to your good health” below.) Fortunately, about a year or two ago, responsible supplement suppliers began to make individual folate (not folic acid) supplements available. Some suppliers have just started to include various forms of folate in multiple vitamins and other combinations.

So it’s time to make folic acid supplements a part of history, and use only forms of naturally occurring folate when we use supplements. A little bit of folic acid (100 to 200 micrograms, the amount found in many multiple vitamins at present) is not likely to be a problem, but more taken daily for years just might raise your long-term risk of colorectal cancer or cognitive decline. If higher amounts are unavoidable (for example, until all prenatal vitamins switch from folic acid to folate), taking additional folate will very likely offset the folic acid still found in the multiple. If you’re apprehensive, consult a physician skilled and knowledgeable in nutritional and natural medicine.

It’s very likely that within a relatively short time enough responsible supplement suppliers will switch from folic acid to folate in all their supplements, individual and combination, so you won’t need to read all the labels so closely to make sure you’re getting folate and not folic acid.

One last point you may be wondering about: Is there such a thing as “too much of a good thing” when it comes to naturally occurring folate supplementation?

Unless you have vitamin B12 deficiency or cancer, it’s very unlikely to be a problem. In the case of vitamin B12 deficiency, supplemented folate—even naturally occurring folate—can “cover up” some of the deficiency signs in blood tests. But preventing that is simple: Take extra vitamin B12 whenever you take extra folate! Some suppliers even combine the two, or put them with the rest of the B-complex vitamins.

But if you have cancer, it’s of course best to discuss folate (not folic acid) supplementation with a physician skilled and knowledgeable in nutritional and natural medicine. To find one in your area, contact the American College for Advancement in Medicine. JVW

Where to get it: Naturally occurring folate in supplements

At present, two types of folates that occur naturally in foods are available as over-the-counter supplements. One is folinic acid, usually sold over-the-counter as “calcium folinate.” Calcium folinate is also available by prescription as Leucovorin®, which, unfortunately, is considerably more expensive and also contains FD&C yellow #10 and FD&C blue # 1, neither of which improves clinical results.

The other over-the-counter naturally occurring folate presently available is 5-methyltetrahydrofolate. It’s more expensive than over-the-counter calcium folinate, but more likely to be effective for individuals with “hidden” genetic defects in folate metabolism.

There’s also at least one B-complex and one multiple vitamin-mineral combination containing calcium folinate and methylcobalamin (the more metabolically active form of B12) available over-the-counter. By the time this newsletter is printed, it’s very likely more than one of each of these will be available, too.

The availability of supplemental folates that occur naturally in foods has solved another problem I’d been observing in a minority of individuals since the 1970s. Although the large majority of people who tested poorly for individually optimal levels of folate on a test called the neutrophilic hypersegmentation index (see “Overlooked blood test could be the key to your good health” below) significantly improved their levels by taking folic acid supplements, a small but significant number had little to no improvement at all. For this group, all I could tell them was to eat as much folate-containing food as possible, and forget the folic acid supplements.

But since supplemental calcium folinate and 5-methyltetrahydrofolate have become available, nearly every patient with a previously abnormal neutrophilic hypersegmentation index has improved with their use.

Overlooked blood test could be the key to your good health

If you’re serious about good health and longevity, or if you have any chance at all of becoming pregnant, there’s an inexpensive but critically important blood test that’s too often overlooked. Although it’s simple, quick, and easy to do, many clinical laboratories don’t do it because there’s “no demand.”

It’s called the “neutrophilic hypersegmentation index.” It is a mouthful to say, but for decades it has been—and still is—the best test of your personal folate status. Not how your folate level compares with other peoples’, but how optimal your own level is.

To do that, the neutrophilic hypersegmentation index (NHI) determines what percentage of your neutrophils—a type of white blood cell—were supplied with an optimal amount of folate while they were growing and maturing. Of course, optimal is 100 percent. But before we get into how to boost your own score, it’s important to know some of the scientific background that explains why this test is so important.

When neutrophils are “born” and “incubate” in bone marrow, their chromosomes—DNA—arrange themselves into five segments. A final step in neutrophil DNA maturation is re-arrangement of those five segments into three. Normal folate metabolism is a key to this final step. Very shortly after the five-to-three segment DNA re-arrangement, the fully mature neutrophil is released from the bone marrow into the bloodstream, where it lives out its months-long life doing its job—one very important part of which is defending our bodies against germs.

But if there isn’t enough folate, the neutrophil’s DNA stays in five (instead of three) segments. When the neutrophil is needed, it’s released into the bloodstream anyway, where it’s called a hypersegmented (too many segments) neutrophil. Fortunately, a hypersegmented neutrophil can still fight germs as well as a “regular,” three-segmented neutrophil.

Planning a family? Why you MUST have this test

After a blood sample is drawn, a technician with a microscope can easily see and count the number of DNA segments in each neutrophil. The “hypersegmentation index” is the percentage of five-segment neutrophils counted in a total of one hundred neutrophils.

Neutrophils, other circulating blood cells, and the cells that line our gastrointestinal tracts are the most rapidly dividing cells in our bodies. So if there’s a shortage of any of the three key nutrients for keeping cell division normal—folate, vitamin B12, and/or zinc—these rapidly dividing cells are likely to show the effects first. So the “neutrophilic segmentation index” actually tells us whether the most rapidly dividing cells in our bodies have enough folate. If these cells do, then it’s very likely that every cell in our bodies has enough folate.

One of the saddest test reports I’ve had to share with anyone was an NHI of 47 percent reported for a woman who was already pregnant. As you may have expected, her baby was born with a birth defect.

Every woman who has any chance at all of becoming pregnant should have this test done! If it’s abnormal, and she’s planning on a pregnancy soon, she should take a series of folinic acid injections (see above “Where to get it: Naturally-occurring folate in supplements”. ) right away, preferably with the methylcobalamin form of vitamin B12, so there’s enough folate (and B12) immediately available for any newly conceived infant.

Why the rush? Well, the most common birth defect—neural tube defect—occurs on days 27–29 after conception, before many women are even certain that they are pregnant.

For the rest of us (as well as newly-folinic-acid-injected potential moms) an abnormal NHI means you need to take a closer look at your diet and make some necessary adjustments—most notably adding in more sources of folate, particularly green vegetables, beans, peas, brewer’s yeast, and (organic only!) liver. A folinic acid or methylfolate supplement is important, too, at least until the test normalizes.

A basic nutrient for cancer and heart disease protection

But pregnancy—or the possibility of pregnancy—isn’t the only time folate levels are important. Folate (along with vitamin B12 and zinc) are all critical to normal cell division and DNA repair, which means they’re all essential tools for cancer prevention. Adequate folate lowers the risk of a variety of cancers, particularly in the gastrointestinal tract, but also breast, pancreatic, cervix, and lung.

It’s almost certain further research will add other cancers to this list. However, for those who already have cancer in any form, it’s not yet clear whether or not supplemental folate may accelerate cancer growth as fully oxidized folic acid has been found to do in some studies.

Along with vitamins B6 and B12, folate helps keep levels of the natural human metabolite homocysteine low in our bodies. Considerable research shows that increasingly higher homocysteine levels are associated with increasingly higher levels of cardiovascular disease and atherosclerosis.

It’s true that in 2008, researchers reported that supplemental folic acid (not folate), B12, and B6 were effective at lowering homocysteine but were ineffective in reducing “major cardiovascular events” and deaths, but (once again) it’s very likely that this study used folic acid—which isn’t as easily metabolized in older individuals (rather than methylfolate)— along with less-than-optimally active forms of vitamin B12 and B6.

So, despite this (likely flawed) study, if your homocysteine levels are high, I still recommend eating more folate-containing vegetables, and, if necessary, taking enough supplemental methylfolate, methylcobalamin, and pyridoxal phosphate to keep your level low. If you do, your risk of cardiovascular disease and atherosclerosis will likely be lower, too.

Research indicates that other benefits of supplemental folate may include reduction of stroke risk and macular degeneration, and improvement in depression, as well as improvement in memory and mental agility in older individuals.

When enough is enough

I’ve been using this test as part of routine “good health” testing for nearly everyone for over 30 years, and rarely see a result of under 5 percent (which shows insufficient folate). So the goal is always to bring that level as close to 0 percent as possible.

But if you want to be really “engineering precise,” a level of 1 to 2 percent hypersegmented neutrophils—meaning that 98 to 99 percent of those white cells received enough folate—may be the best outcome to aim for. Why isn’t 0 percent even better? An engineer friend once explained it like this: “Once I get to 0 percent, there’s no -10 or –20 percent reading to tell me that it’s 10 or 20 percent more than I really need, so I’m going to keep mine very slightly under rather than go over.”

It’s a good point—and leads to the next question: Is there any danger of “overdose” with folate? Except when cancer is already present, it’s not very likely. I’ve never seen it happen in over 35 years of practice. But no one knows for certain. So keeping your NHI at a level of 1 to 2 percent ensures that your folate levels are optimal without “overdoing” it.

And increasing folate-containing foods in the diet and (in the majority) adding supplemental folate almost always brings the test to that optimal level.

The NHI is simple enough to be done by any laboratory with a microscope and a skilled technician, but many labs still don’t do it. Why? Well, it requires a smear of blood on a microscope slide and isn’t done by machine. However, blood specimens can also be sent to Meridian Valley Laboratory in Washington state, where state law makes it possible for individuals to order their own lab tests.

JVW 

Products 

Be sure to get $10 off your first VitaCost vitamin order.

Jett & I take: http://www.vitacost.com/Source-Naturals-MegaFolinic It divides well with a pill cutter & then I crush it to make sure he can ingest it.

and I also take: http://www.vitacost.com/Metagenics-FolaPro-60-Tablets but, it's a tablet and gets destroyed if you want to divide it, so next time, I'm getting this one:

I included both of these because folinic acid is used for some ARN and ADN synthesis and methylfolate is mainly used for methionine regeneration so both are needed see: http://www.knowyourgenetics.com/The%20Methylation%20Pathway_files/supplmentation-1.jpg
Supposedly moms with MTHFR mutation or methionine sintasa mutation will benefit more from methylfolate. (I don't know if I have it, but I'm just assuming I do because of the symptoms and the fact that Jett has DS.)


Children with DS who don't have the same mutation as the mother will benefit more with folinic acid, but some of them also carry the same mutation as the mother and some of the father too.
Some with DS react adversely to folinic acid because they seem to have the mother and or father's mutation because folinic acid converts back to folic acid. (But you would know if it caused a problem by now.)

So you can test your child for those mutations too or check how s/he reacts to folinic acid and other methyl donors if s/he is ok with that, probably just folinic acid is best for him rather than methylfolate because if he does not have the mthfr mutations his methylfolate can accumulate.

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Thursday, May 26, 2011

Six Year Old Mac Austin: In the News



Here's a link to a news story that was done on Mac Austin, a six year old with T21 who is on the Changing Minds Foundation treatment suggestion:


VIDEO: Researching Down Syndrome 10pm 5/12/2011
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Play_Now_Button
You can also try this link if the play button doesn't work.

http://www.nbc15.com/video/?autoStart=true&topVideoCatNo=default&clipId=5846095&flvUri&partnercli

More about Mac Austin:

Meet six year old Mac Austin. His mother, Lexy, found out about the Changing Minds Foundation treatment plan from a Google search. Her interest lead her to the CMF conference which she attended last July with her mother. Bursting with lots of new information, they were both very excited to get back home and start Mac on the protocol. They have seen some major changes in him and are excited to share this information with the DS community.

According to Lexy, Mac went from using one word to communicate before the protocol, to using three and four word sentences. Mac is keeping up with his first grade classmates in learning his spelling words -- six words a week! Last year it took him two weeks to learn one sight word!!

He is acknowledging when people speak and saying, "Hi!" in response. He's also asking questions and initiating conversation.

"He is engaged now, has better eye contact, he is just here with us!" says his mom. He is playing and interacting with his friends at school, a skill he used to have and lost during his regression over the last two years.

Mac can dress and undress himself, which he could not do before the protocol.

His language continues to improve. He is saying words and phrases that he has never said before like:

"It's Griffin's turn."

"Mom, put me to bed, please."

"Turn computer off."

"How about that one?"

Mac takes Prozac (started June 1st, 5mg), Ginkgo Biloba (started Aug. 1st, 160mg), and Body Bio Balanced Oil (started end of Aug. 1tsp). They will be adding the PC soon. Mac is 43" tall and weighs 48 lbs.

Video of Mac reading a book.

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Jett "Reading" at 16 Months

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Wednesday, May 25, 2011

L-tyrosine: Building Block for Neurochemicals

Hopefully, you are aware that the DS population has a high incidence of hypothyroidism -- with some sources saying that 100% have, or will develop, thyroid problems in their lifetime. (Learn more at Thyroid & Down Syndrome.) Issues related to the lack of available tyrosine (and/or available iodine) have also been found in those with DS. Since the primary thyroid hormone (T1) is composed of iodine and tyrosine and since some people with DS have difficulties converting phenylalanine into tyrosine, it appears logical that this may contribute to the prevalence of hypothyroidism and that supplemental tyrosine may help. (See more below.)

So, Jett takes 100 mg of l-tyrosine in the morning and afternoon, a half-hour before meals or an hour after meals in order to best metabolize it. Years after Jett had starting taking tyrosine, I had run out. Coincidentally, I got an amino acid panel done on him and it did show that he was low on tyrosine and that I needed to continue supplementation. 

What is Tyrosine?

It's a nonessential amino acid that is synthesized in the body from phenylalanine. As a precursor or building block for several important neurochemicals, tyrosine builds dopamine, epinephrine, and norepinephrine, all of which work to regulate mood. According to the study Disorders of phenylalanine and tyrosine metabolism in Down's syndrome, issues with tyrosine appear to be one of the factors responsible for disturbance of neurotransmitter synthesis and to be related to poor brain function.

Other benefits of tyrosine

 Antioxidant Tyrosine is a mild antioxidant as well as having supposed antidepressant effects.

 Overcome Depression Tyrosine is the amino acid and inhibitory neurotransmitter that often helps overcome depression. Clinical studies show that tyrosine controls medication-resistant depression.

In a 1980 issue of the American Journal of Psychiatry, a study by Dr. Alan Gelenberg of Harvard Medical School discussed the role of tyrosine in the control of anxiety and depression. Dr. Gelenberg postulated that the lack of available tyrosine results in deficiency of the hormone norepinephrine at a specific location in the brain that relates to mood problems such as depression. Children given tyrosine supplementation demonstrated a marked improvement in mental performance and mood stability.

Reduces Stress (and stress related behavior) Tyrosine, because of its role in assisting the body to cope physiologically with stress and building the bodys natural store of adrenaline, deserves to be called the stress amino acid. Stress exhaustion requires tyrosine. During periods of stress, in order to continue coping with stress physiologically, the brain requires tyrosine. Tyrosine aids children and young teens, as well as adults, with recurrent depression and mood disorders. In children, dosage ranges from 200 to 500 mg daily. (See below for more about the adrenals.)

 Helps with ADD symptoms (see below).

 Reduces DYRK1A levels, which is a contributing factor to mental capacity in those with DS (see below).
Pain Relief Because tyrosine is also involved in the synthesis of enkephalins (opioids), substances that have pain-relieving effects in the body, it appears to have some added pain relief benefits. (Not usually a problem in this population, though.) Tyrosine seems to be especially beneficial when used in conjunction with 5-HTP. (Or l-tryptophan, which Jett used to take but is sufficient in it now.)



 Tyrosine & Thyroid

 Hypothyroidism is a serious condition that affects glucose metabolism, blood calcium concentration (and therefore ionic balance) and bone density. It can impair growth and cause mental retardation. Iodine deficiency also causes hypothyroidism.

Thyroid hormones are produced from the amino acid Tyrosine (present in commonly consumed food items such as meat, dairy, and eggs) and iodine (found in iodised table salt, kelp, and fish). Functional niacin deficiency (as a result of high tryptophan demands) can result in poor stomach acid that will directly impair digestion of proteins. HCl - stomach acid - activates the enzyme peptidase that is responsible for the main breakdown of proteins. If the stomach produces weak acid, (also a common problem in DS) clearly, protein digestion will be impaired. This means less tyrosine available for the production of thyroid hormones and may result in hypothyroidism.

L-Tyrosine is essential for certain thyroid and adrenal hormones . It is considered to be a non-essential amino acid, which means that if everything is working correctly in the body (which is not always the case with DS), it can convert phenylalanine into tyrosine. However, since it has a synthesis component limited by phenylalanine oxidation, there appears to be more problems producing sufficient quantities of L-tyrosine than other non-essential amino acids. And this is more of a problem in those with DS, probably because the activity of phenylalanine hydroxylase is impaired in the liver of those with DS.

There are apparently other tyrosine issues for those with DS. Even in utero those with DS have a 50% overexpression of the kinase DYRK1A (DYRK1A
is an abbreviation for dual-specificity tyrosine (Y) regulated kinase 1A), which is partially regulated by tyrosine – it may be that this overexpression
of DYRK1A further reduces the available tyrosine for those with DS. DYRK1A is considered to be a candidate for causing the mental retardation and some of the other negative side effects associated with DS. It is possible that consumption of supplemental tyrosine or certain peptides might result in reduced DYRK1A levels (as one such peptide has been successfully tested, [24]), and hence be of benefit to the DS population.

 Prefrontal cortex problems (typical ADD like symptoms)
originally from http://www.docamen.net/bp/care/supplements.php (since been removed) written by MD and neuroscientist, Dr. Daniel Amen


People with PFC (prefrontal cortex problems) seem to have lower availability of the neurotransmitter dopamine. The amino acid L-tyrosine in doses of 500-1500mg two to three times a day for adults and 100-500mg two to three times a day for children under 10 can help. L-tyrosine is the amino acid building block for dopamine. It is reported to increase the level of phenylethylamine (PEA), a mild stimulant that is found in high concentrations in chocolate. Many of my patients have reported that it is helpful for them. It is softer in its effect, but nonetheless they notice a positive effect. Because of absorption patterns I recommend that they take it on an empty stomach (a half-hour before meals or an hour after meals). I have not seen any side effects with L-tyrosine, except for mild weight loss. If there are cingulate problems, l-tyrosine by itself can increase the intensity of overfocused symptoms. Symptoms of tyrosine deficiency include hypothyroidism, low blood pressure, low body temperature (cold hands and feet), and restless leg syndrome. (Jett had all of these symptoms.)
What is the prefrontal cortex?

This area of the brain is thought to be involved in planning complex cognitive behaviours and in the expression of personality and appropriate social behaviour. The prefrontal cortex (PFC) is the very front of the brain, located right beneath the forehead. It is in the anterior (front) region of the frontal lobes. Besides being the front of the brain physically, it is responsible for the executive functions, which include mediating conflicting thoughts, making choices between right and wrong or good and bad, predicting future events, and governing social control — such as suppressing emotional or sexual urges. The prefrontal cortex is the brain center most strongly implicated in qualities like sentience, human general intelligence and personality.

Dosage

As seen above, in children, dosage ranges from 200 to 500 mg daily or 100-500mg two to three times a day. Jett's doctor recommended he take 100 mg of l-tyrosine in the morning and afternoon, before he eats anything. From an NAET visit Jett showed that, at 3 years old, he still needed it.

For products, see the DS Day to Day amazon store.

If you purchase from vitacost, be sure to get $10 off your first order.
Precaution

Tyrosine aids in the production of melanin (pigment responsible for hair and skin color). Those with pre-existing pigmented melanoma should avoid tyrosine supplements, as it is suggested that tyrosine may increase the ability of the melanoma cells to spread. It's unusual for people with DS, however, to get cancers other than leukemia.

Before taking any nutritional supplement, including amino acids, please first consult your health care provider.


 Sources

http://www.neurogenesis.com/Amino-Acids/tyrosine.php
http://www.docamen.net/bp/care/supplements.php
Article Autism: Mercury Induced Pellagra and Cretinism?
http://intelegen.com/nutrients/add.htm
http://www.healthresearch.com/downsyndromethyroid.htm

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