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» LymeNet Flash » Questions and Discussion » Medical Questions » Bb needs our choline...how the neurotransmitter acetylcholine is impacted

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Author Topic: Bb needs our choline...how the neurotransmitter acetylcholine is impacted
Marnie
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This is a repost because no one replied. It is very important that you understand what is happening when infected with a pathogen that is taking your supply of choline.

Acetyl CoA + choline (a B vitamin) = acetylcholine OR another way to put it = acetic acid and choline. = acetylcholine.

It is an excitatory neurotransmitter. So is glutamate. Acetylcholine is used, broken apart and rebuilt. The breaking apart enzyme is called acetylcholinesterase and it works incredibly fast...breaking up acetylcholine molecules in about 80 microseconds.

Backing up a second...there are many neurotransmitters in the central nervous system, but the peripheral nervous system has only two - acetylcholine and norepinephrine.

Where does acetyl Co A come from?

In the breakdown of foodstuffs, pyruvate derived from carbohydrate and fatty acids derived from fat are converted to acetyl-CoA by the intramitochondrial(inside the powerhouses of the cells) enzyme systems.

Fatty acids are broken down to release acetyl CoA which combines with choline to make acetylcholine.

Acetyl CoA is also a precursor to HMG CoA. HMG CoA uses the enzyme, HMG-CoA Reductase, to produce mevalonate. HMG CoA reductase is the trigger for the cholesterol pathway. Magnesium and statin/arbs drugs INactivate this enzyme and thus stop excess cholesterol formation in the liver.

This is the pathway that Bb takes (the mevalonate/cholesterol pathway)...along with the glycolysis (sugar) pathway.

Acetyl CoA (from fatty acids) -> HMG CoA + HMG CoA reductase -> mevalonate...the cholesterol pathway. Mg blocks (Inactivates) HMG CoA reductase.

What happens if there is not enough choline?

Liver damage. It is indicated by an increase in a liver enzyme called alanine aminotransferase (ALT). In cell culture, liver cells initiate programmed cell death (apoptosis) when deprived of choline.

Side note: choline is related to intelligence. The more choline available, the ``smarter'' the offspring.

And...

Choline also helps in the production of lipotropic agents which converts fats into useful products and aids in the production of HDL (good) cholesterol.

Choline is used in the synthesis of the phospholipids, phosphatidylcholine and sphingomyelin, structural components of all human cell membranes.

Now, what about the ``excess'' acetyl CoA hanging around if Bb is only using our choline? Normally, it is supposed to be oxidized to form carbon dioxide.

The first four reactions in the citric acid cycle (Krebs Cycle) are catalalyzed (helped along) by isocitrate dehydrogenase, which requires MAGNESIUM for its activity, and is the enzymatic key to the overall rate of this cycle.

But what if Mg is too low? What happens then to the excess acetyl CoA?

Ketone bodies are synthesized from acetyl CoA and the excess accumulation of acetyl CoA will lead to higher levels of ketone bodies in the liver and blood stream. This leads to ketoacidosis.

Now insulin (acidic) is required to get rid of excessive ketones. Oops...insulin ACTIVATES the enzyme PFK which Bb is ``dependent'' on. Insulin activates cholesterol synthesis too! Too much insulin -> cells become desensitized...likely.

And...with Mg low, there goes serotonin (and melatonin which is made from serotonin). Melatonin is synthesized from serotonin in a 2-step process that takes an acetyl group from acetyl-CoA and a methyl group from SAM (S-AdenosylMethionine).

Melatonin is a powerful ``antioxidant''. If melatonin is being overproduced, that might lead to sleepiness/fatigue/slowed down thinking?

Low melatonin has been reported in patients with photosensitive epilepsy - those whose seizures are triggered by strobe lights, etc. Flashing lights impact the sodium channels too.

What happens if someone is ``undermethylated'? (This is a depression subclass.)

Low serotonin, high histamine (allergy trigger). And what's a natural anti-histamine...Mg! In undermethylation the levels of serotonin, dopamine, and norepinephrine are lower and the levels of histamine and basophils are higher. Folic acid is needed for protein synthesis, cellular reproduction, *choline synthesis*, red blood cell formation....no wonder why it is suggested pregnant moms take extra folic acid!

In someone UNDERmethylated, folic acid levels will go UP. They should not take extra....they need extra choline. Choline acts like folic acid, TMG (trimethyglycine) and SAMe (S-adenosylmethionine) to promote methylation.

What the heck is methylation?


Methylation refers to the replacement of a hydrogen atom (H) with a methyl group (CH3).

Methylation
The transfer of a methyl group to another molecule. It makes adrenaline from norepinephrine, and melatonin from serotonin. It is critical for the transcription of DNA.

In biological systems, methylation is catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA metabolism.

Enzymatic addition of methyl (CH3) group to DNA which causes inactivation of that region. So, adding carbon + 3 hydrogens to DNA. If someone is hypermethylated -> to silencing of a gene and total absence of protein production.

Serotonin needs Mg, B6 and 3 other nutrients to be made. The last 3 escape me at the moment, but I can look them up if someone needs to know.

With serotonin low, hello depression. The body will try to make more serotonin initially, pulling the nutrients from storage to do so.

We need nutrients to make serotonin and if we have those nutrients and don't need extra serotonin, they can be converted to make niacin. The SSRIs prevent the breakdown/storage of serotonin. Prozac works by locking onto an acetylcholine receptor, blocking this excitatory neurotransmitter, keeping serotonin up.

Too much niacin, however can deplete choline, so ``heads up''.

Poisons and toxins attack the enzyme that is needed to breakdown acetylcholine and cause it to accumulate in the nerve synapse (junction) which can paralyze muscles.

Doctors are now intentionally destroying/blocking acetylcholinesterase to reverse the symptoms of Alzheimer's. Thus allowing more acetylcholine to strengthen the nerve signals that remain.

It appears in Alzheimer's the acetylcholine producing cells have become exhausted. At high concentrations of acetylcholine, the affinity for acetylcholine becomes higher and the receptor subsequently becomes desensitized.

The enzyme that breaks down acetylcholine, once again, is acetylcholinesterase. This enzyme breaks down the neurotransmitters GABA and serotonin. GABA (and glutamic acid) are considered the ``work horses'' of the brain.

Magnesium blocks acetylcholine release. So does angiotensin II! If someone is Mg deficient this would logically result in too much acetylcholine constantly released. The body counters the Mg deficiency by a calcium influx into the cells which triggers TNF alpha and then angiotensin II which does inhibit acetylcholine release. Long and harmful way around a problem. The body is trying to find an alternative pathway.

Within the brain, the cholinergic system is suppressive (parasympathetic.). That means when acetylcholine levels rise, the brain generally becomes less active; nerves are less able to 'fire'.

Acetylcholine up/Mg deficiency triggers very damaging free radicals and free radicals also contribute to PKC's activation. It also stimulates an increase in calcium.

Also, an elevated level of acetylcholine -> an influx of sodium through a ligang-gated ion channel.

Acetylcholine reduces intraocular pressure.

Too much acetylcholine may impact cortisol levels. Cortisol is also synthesized from cholesterol.

Valium often is given as an antidote in conjunction with atropine to counteract seizures which may develop due to elevated levels of acetylcholine.

Acetylcholine may contribute also to an increase in free radicals...good and bad. It appears free radicals trigger PKC, but damage the mitochondria - the powerhouses. Bb contains a PKC Inhibitor...PKC may ``compete'' with Bb's inhibitor.

On the other hand, if acetylcholine is too low...

Low levels of gastrin and acetylcholine (or Mg) -> too much stomach acid produced.
(An autistic symptom ie., too much stomach acid produced.)

And...

"Low acetylcholine levels contribute to the forgetfulness and lack of ability to concentrate which often occurs in old age.

The cholinergic nervous system also controls the sensory input: too little acetylcholine and you are easily distracted by stimuli in your environment, whether you are trying to think (loss of concentration) or sleep (awakening too easily).

(The above sorta sounds like ADHD, doesn't it?)

In addition, too low acetylcholine levels cannot support normal motor (muscular activity) control and coordination and motor response falter.

Finally, acetylcholine is an important motivational chemical, along with the catecholamines."

Acetylcholine acts through inhibitory circuits to turn on nerve cells that send messages horizontally across the cortex and to turn off nerve cells that send messages vertically.

Acetylcholine is acting like a traffic cop in the cortex, directing the flow of information -- the nerve signals -- along the cortical highways. Acetylcholine during a brief stage in fetal development is ``critical for the assembly of the spinal circuitry that controls our most basic movements.

Remember...folic acid to make choline to prevent birth defects...

Acetylcholine, nicotine and choline might help to reduce glutamate induced excitotoxity. If CoQ10 (which needs B6 and Mg to be made) is deficient, nerve cells in the brain and elsewhere may not have the ability to withstand the overstimulation caused by excess glutamate.

But... Acetylcholine release can be excitatory or inhibitory depending on the type of tissue and the nature of the receptor with which it interacts.

Keep in mind too...acetylcholine is the neurotransmitter needed during REM sleep which is WHEN we make PROTEINS...including enzymes, hormones, immunoglobulins...these are all proteins.


Too much, not good. Too little, not good. Balance. It's all about the balance.


Now let's go back to the cholesterol pathway for a moment. If HMG CoA reductase (an enzyme) remains active, this would lead to much greater cholesterol formation. Higher cholesterol levels.

High level of cholesterol produces endothelial dysfunction because it REDUCES the bioavailability of NO (nitric oxide).

NO is "involved in virtually all endothelium-dependent protective effects".

We know that Bb heads for the endothelial cells. These cells line the blood vessels and are right next door to the connective tissue (3 kinds- one rich in fats).

NO inhibits vasoconstriction, platelet aggregation, smooth muscle cell proliferation and leucocyte adhesion.

The increase in free radicals (due to Mg deficiency/excess acetylcholine) also INactivates NO.

And hypoxia (not enough O2) also causes endothelial dysfunction, in part, by decreasing endothelial NO synthase (eNOS) expression and activity.

We need the blood vessels to dilate, to deliver more oxygen and nutrients...NO and acetylcholine can do this....and so does exercise!

The statin drugs (and Mg) have the ability to increase NO availability and they lower the LDL levels (lousy cholesterol). Cholesterol is made from proteins + fats. The good kind, HDL, has more protein than fat. The lousy kind, LDL, has more fat than protein. HDL contains an enzyme that is a powerful antioxidant and prevents the oxidization of LDL cholesterol. Cholesterol is beneficial and without harm if it is not first oxidized.

High levels of LDL DOWNregulate eNOS (endothelial nitric oxide synthesis) and mRNA and protein expression. NOT good!

The mevalonate pathway (the cholesterol forming pathway) specifically regulates eNOS.

The statins (and Mg) MIGHT be related to their antioxidant effect also, it has been suggested.

Now, look closely at the following:

NUTRIENTS THAT FORM BRAIN CHEMISTRY

The brain and central nervous system need the following nutrients to function: Vitamin A... Beta-carotene ...Vitamin B-1 (thiamine)... Vitamin B-3 (niacin) ...Vitamin B-5 (pantothenic acid)... Vitamin B-6 (pyridoxine) ...Folacin (folic acid)... Biotin... Inositol ...Vitamin C ...Vitamin E... Calcium ...Magnesium Phosphorus... Potassium.... Iron... Manganese... Chromium... Iodine... Molybdenum

Nutrients that constantly repair the brain tissues: Vitamin B-12 (cobalamine)... Folicin (Folic Acid) Vitamin B-1 (thiamine)... zinc

Nutrients that slow down the fatty tissue accumulation in the brain: Vitamin A... Vitamin E...Vitamin C Selenium

Nutrients that create brain fuel: Vitamin B-1 (thiamine) Vitamin B-2 (riboflavin) Vitamin B-3 (niacin) Biotin Vitamin B-5 (pantothenic acid) Magnesium Chromium

The nutrients needed to move glucose into the brain to create energy: Vitamin B-1 (thiamine)... Vitamin B-3 (niacin) ...Vitamin B-2 (riboflavin)... Biotin ...Vitamin B-5 (pantothenic acid)... Magnesium Chromium

RECIPES FOR BRAIN CHEMICALS

Vitamin B-3 + Vitamin B-6, Vitamin C, Folic acid, Copper, Iron and Zinc = Phenylalanine & Tyrosine which creates Norepinephrine and Dopamine

Folic Acid + Vitamin B-12, Vitamin B-6, Protein, Iron, Zinc and Copper = Brain Oxygen

Vitamin B-6 + Magnesium = Choline which changes to Acetylcholine. Also changes to Phenylaline and can increase Dopamine

Tyrosine + Iron, Vitamin C, Vitamin B-3, Vitamin B-6, Magnesium, Zinc, Copper and Manganese = Serotonin

Vitamin B-6 + Tryptophan = Norpinephrine and Serotonin

Tryptophan + Vitamin B-6, Vitamin C and Iron = Norepinephrine or Dopamine

http://www.chemicalbalance.com/part_one_manual.htm

We know that the antioxidants, vitamin A and E drop in lyme. These nutrients are needed to slow down the fatty tissue accumulation in the brain.

And do you see (above) where Mg and B6 are needed to produce choline -> acetylcholine?

Cholesterol is made, broken down, and made constantly. Normal healthy adults synthesize cholesterol at a rate of approximately 1g/day and consume approximately 0.3g/day. A relatively constant level of cholesterol in the body (150 - 200 mg/dL) is maintained primarily by controlling the level of de novo synthesis.

The level of cholesterol synthesis is regulated in part by the dietary intake of cholesterol. Cholesterol from both diet and synthesis is utilized in the formation of membranes AND in the synthesis of the steroid hormones (estrogen and testosterone are protective) and bile acids. It also forms the myelin sheath...the insulation around our nerves.

So, bottom line. Bb heads for the endothelial cells where it damages them. It locks onto a heparin receptor where it likely uses fibrin to cloak and might make it harder for the antibodies to reach the pathogens. It is after our choline, a B vitamin. Bb follows both the glycolysis and cholesterol pathways.

This impacts the level of acetylcholine, a major neurotransmitter and our cholesterol levels. For many PROTECTIVE reasons, magnesium levels drop ``significantly'' very fast (pulled from storage) and this begins a downward spiral impacting many other nutrients as well.

Magnesium is stored as Mg-ATP inside the cells. Not much is in ``general circulation''. This disease causes a very toxic - acidic condition. This is very unhealthy because we are supposed to be slightly alkaline. We must raise the pH...make a LOT more hydrogen and get it into the cells to INactivate the ``rate limiting'' enzyme PFK which Bb is ``dependent on''. With choline levels dropping, this will impact the liver...our major detox organ that deals with acidic conditions.


In one sentence or less:

Low Mg -> calcium influx -> TNF alpha -> angiotensin II -> inhibition of acetylcholine release.

If Mg levels were restored...adequate Mg would do the same...lower the level of acetylcholine without causing the damaging calcium influx, the rise in TNF alpha and the rise in angiotensin II. The body, it appears, is trying to lower the amt. of acetylcholine. It takes the right balance of Mg and Ca to make HEALTHY antibodies.

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5dana8
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Thanks for this information marnie [Smile]

This is very important information but right now
I can't read a long page of print so I am going to print this out and read it in small incerments.

Take care and Blessing to you for keeping us up to date.
I appreciate all your help LOL

--------------------
5dana8

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danielb
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yeah i'm sorry. i am very interested in acetylcholine and lyme, and also how ACh affects other conditions, or how lyme causes other conditions with the ACh-related problems.

i just find it all so difficult to follow.

even when i didn't know it was lyme, i had tried two pills that are acetylcholine based. DMAE (supplement, apparently transform into ACh in the brain, but this is disputed.) Aricept (Rx'ed med, AChE inhibitor, expensive, think it may have caused an initial deep depressive response...). i didn't continue either pills, DMAE may have made me clearer but wasnt sure, Aricept apparently helped someone significantly with fluency issues after one month but i stopped it due to the VERY long half-life (trouble if you all of the sudden find someone to do a SPECT scan) and it was very expensive. i know have a significant amount of both saved up though, i'm just not sure how they would help.

I also have Phosphatidylcholine which I am forgetting to take. [Frown] don't know what it does either.

you mention that ACh overload is also a problem, not ACh shortage then? ahhh... see i am going to have to read this all again. i get very easily confused, so it is all so difficult even though it it is interesting and significant with me. the only thing that registers with me is what good meds to take, but then they always seem to be expensive, complicated, and only 'may' help, and then it may not even be noticable and not help my life... [Frown]

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sarahinnewyork
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Hello,

Thanks for the great post Marnie!

I am also very interested in this- and although I find it difficult to digest I really appreciate the thorough explanations!

I have started putting liquid lecithin in my yogurt in the mornings as a result of the recent posts.

My breakfast is non fat plain yogurt with a couple of tablespoons of liquid lecithin, flaxseed oil, kiwifruit ( usually the only fruit in my day-)and big spoon of cinnamon to regulate blood sugars.

Is there anything I should be eating with the lecithin to improve it's affect?

As an aside, I sometimes add in a packet of gelatine as I'm on Levaquin and I hope that it might help with collagen production and protect my joints and tendons-

I'm interested to know how others are supplementing their acetylcholine supplies...

Cheers,
Sarah

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ebrischoux
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Thank you Marnie for this info....I do not have lyme and I am having a hard time digesting all this info too...

I am going to print out and try and decipher it as best I can because I think it is really important and I am desperately trying to help my son....

You are a wealth of information and I thank you...Eileen

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Carol in PA
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Marnie,
I copied this into Wordpad and printed it out. Much easier to read and digest that way.

Thank you.
Carol

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mikej2323
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Marnie-

Very good post--I have a niece who has slowly become paralysed over the last 10 months. It began with her left arm, then left leg. It then went to her right arm and finally, her right leg. Right now, her nutrition is through an IV, but I was curious what supplements to give her to make acetylcholine?

Thanks.
Mike

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Marnie
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Maybe I better clarify this...looks like there is too little choline and too much acetyl CoA.

The excess of Acetyl CoA is doing damage.

The lack of choline is doing damage.

These are impacting the liver...our largest "detox" organ which should be coming to the rescue, but can't..."fatty liver".

The minerals, Mg and P are impacted.

The vitamins, choline - which is a B vitamin, B1 and B6 (esp. - but all the Bs work together) are impacted.

We have to restore the balance.

This pathogen, like all of them...are parasites. They take from us nutrients that they need, but we need those nutrients too...to fight, to stay healthy.

Let me give you an example:

SARS was first identified in 2003, originating in China and spreading rapidly to Asia, Canada and elsewhere. It killed nearly 800 people and disrupted travel, economics and even some scientific meetings.

The researchers found that the SARS virus binds to the ACE2, Penninger said in a telephone interview.

If disabling ACE2 allowed lung damage to occur, the researchers wondered whether

providing more of the enzyme would help.

They created more ACE2 and infused it into the mice.

The result was to protect mice from the lung failure effects of SARS.

It was effective in two ways, Penninger said.
First, ACE2 combined with the virus and prevented it from binding to normal cells. Also, the enzyme protected the mice from acute lung failure.

Bb does lock onto a heparin receptor and heparin can help...a lot, but a strain that is resistant to coumarin was identified (PMID: 7928965)

Because this pathogen can mutate so easily, we have to rely on our own highly targeted specific antibodies to knock out this infection. Our own antibodies are only "healthy" if there is enough Mg and Ca to make them. Sorta like making a correct copy of a key to fit into a lock. If it is "miss-cut" it doesn't work.

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danielb
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i notice that certain high potency b complexes have choline.

my timed release swiss one as an example (because i am poor). i take it twice a day. i'll copy the list on the back:

B1 (Thiamine HCl) - 100mg
B2 (Riboflavin) - 100mg
B6 (Pyridoxine HCl) - 100mg
Niacinamide - 100 mg
D'Pantothenic Acid (Calcium D'Pantothenate) - 100mg
B12 (Cyanocobalamin) - 100mcg
Biotin - 100mcg
Folic Acid - 0.4mg
"LIPOTROPHIC FACTORS" (???)
Choline Bitartrate 100mg
Inositol 100mg

(edited to add that it also lists 100mg of "PABA" under non-medicinal ingerdients)

I'm pretty sure I have seen B complexes with even more choline, and biotin too. I even saw one that added some Alpha Lipoic Acid. Are good B complexes a good thing to take for Choline, and other B related vitamins or nutrients? If so, what should we look for in a B vitamin, and how many times a day should you take it?

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Marnie
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Paralysis???...are you absolutely certain it is lyme and not Myasthenia Gravis?

Quite the "opposite"...Mg should never be given.

To treat Myasthenia Gravis, doctors at Northwestern Hospital in Evanston, Illinois...specialist...remove the thymus = cure.

Steroids will have to be taken the rest of the person's life, but it worked...

I know this because a close friend's son years ago (at age 17) got this (rare!).

They had been out west on at a "dude ranch", but live in a forested area in Illinois.

He is now well...completed college and is married. He looks great.

VERY important the right dx is made!

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danielb
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if we know that acetylcholine needs to be replaced, how does one do this with what little money many lyme patients have? huge amounts of acetyl-L-carnitine are very expensive... is there anything else?
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Sue vG
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Marnie,

Thank you so much for this wealth of information. I'm on my way to the health food store after work and just added choline to my list.

Sue

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danielb
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hmm... is there a reason the country life choline 650 vitamin has calcium in it. does it help or is calcium necessary to cholinergic function in some way?

http://www.country-life.com/moreinfo.cfm?Category=15&Product_ID=206

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Marnie
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IMO...lecithin is a better choice...supply phosphorus and choline.

(Along with the other B vits and Mg, 'natch.)

Minerals are usually found in combo with acids.

Choline is a B vitamin...acidic.

It looks like...eventually... acetylcholine drops, glutamate, it's "co-hort" climbs...too high.

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lapis29
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bumping this because its a fantastic, really educational post.
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astroman
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Dont forget the magnesium kids! Need that for all this to go around in the Krebs cycle.
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lookup
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THANKS Marnie!
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