Episode 144

While there are many foods naturally high in choline, there are also tons of choline supplements out there:  citicoline (also known as CDP choline), phosphatidylcholine, and alpha-GPC (L-Alpha glycerylphosphorylcholine).

In episode 144, Jesse and Scott Hagerman, President of Chemi Nutra focus on alpha-GPC.

Acetylcholine is the End Game for Alpha-GPC

Choline is an essential precursor to the neurotransmitter acetylcholine.  Acetylcholine is a multi-tasker in the brain and body, playing important roles in activating muscles, attention, responsiveness to sensory stimuli, motivation, learning, memory, and REM sleep.

It’s a natural compound and is biosynthesized by the body from foods like eggs and liver are particularly high in choline.  Choline is then turned into acetylcholine.

In the body, acetylcholine engages muscle fiber and controls muscle movement and power output.

In the brain, acetylcholine keeps you motivated, helps you focus, boosts memory, and aids with learning.

An Efficient Source of Choline

Each form of choline has its strong points, and alpha-GPC has a few unique benefits.

Alpha-GPC is a veryefficient source of choline.  It raises the body’s levels of acetylcholine faster and keeps them elevated for longer.

There are two reasons why:

  1. From a molecular structure standpoint, it has a high amount of choline by weight.  Each molecule of alpha-GPC is 40% choline, while citicoline, for example, is only about 20%.
  2. More importantly, perhaps, is that Alpha-GPC is very polar, so it passes through the brain’s membrane easily, making it very tissue available.

A Significant Nootropic

Although alpha-GPC is prescription only in some countries, it’s not a synthetic drug — it’s a fully natural, highly purified compound.

This unique nootropic is great for both your body and brain.  It promotes human growth hormone, especially when combined with exercise that involves large muscles.  It even boosts physical performance more than caffeine (incredible, right?).

On the cognitive side, it improves memory, focus, and attention.  As Hagerman says, “There’s so much evidence, there’s no reason for us to invest a dime in further studies” on the cognitive benefits of alpha-GPC.

Taking Alpha-GPC

Dosage

  • Minimum:  25mg / day
  • Recommended:  200mg / day
  • Clinical use to treat Alzheimer’s:  1000 – 1200mg / day

Safety
In longitudinal studies, even large doses of 1000mg are safe.  Less than 1% of people experience adverse effects, the most common of which are upset stomach and headache.

It doesn’t negatively affect sleep quality, so no need avoid taking it at night, although some people report vivid dreams after taking alpha-GPC.

How to take it
It’s odorless, tasteless, and stable, and easy to take.  Hagerman suggests mixing it with Kool-Aid for a finished product…

OK just kidding about that last one, but you could if you wanted to. 😉

Episode Highlights

0:22What is Alpha-GPC?
1:37This Week in Neuroscience: ‘Ground Zero’ Brain Region for Alzheimer’s Highlighted
4:46The audience interaction section
8:00Intro to Scott Hagerman
9:36How Scott began working with Alpha-GPC
12:10Corporate versus academic research
14:55Why Alpha-GPC?
16:44Alpha-GPC as a prescription drug for age-related diseases
17:22Alpha-GPC’s mechanism of action
19:37How quickly does Alpha-GPC work and how long does it last in the body?
21:41The highest safe dosages
23:13Is there an optimal time of day to take Alpha-GPC?
23:56What Scott would like to see next in Alpha-GPC research
26:55Cognition studies
29:13Ruthless Listener-Retention Gimmick: Brief rapamycin therapy in middle-aged mice extends lives

PS:  For more memory-enhancing tips, sign up for Brain Breakfast — brain boosting goodness delivered to your inbox every week.

Episode Transcript hideshow

— This Week in Neuroscience --

Jesse: So if you're listening to this episode as it is released, it is currently September, and September is Alzheimer's Awareness Month, so we'll probably be looking for some opportunities to drop some Alzheimer's knowledge on you.  There was a recent review of the Alzheimer's scientific literature by Mara Mather, a professor of gerontology and psychology at the University of Southern California at Leonard Davis School of Gerontology.  It was highlighted in her findings that an important and perhaps underappreciated area in Alzheimer's is a brain region called the locus coeruleus.  This is a little tiny area inside the brainstem, it is apparently bluish in color, and among other things that it does, one of its primary roles is to release the neurotransmitter norepinephrine.  We've talked about norepinephrine before, we actually had a Know Your Neurotransmitters episode of this show talking all about norepinephrine.  It does things like helps regulate heart rate, attention, memory…

But the locus coeruleus is one of the primary areas where norepinephrine is released.  It is also apparently one of the first areas that shows tau pathology in the brain.  Tau is a protein.  It's not necessarily always a bad protein.  But one of the signs of Alzheimer's is what are called neurofibrillary tangles.  You don't want neurofibrillary tangles any more than you want tangles in your hair, and pathological tau proteins seem to be part and parcel of these neurofibrillary tangles.  Now, neurofibrillary tangles do not necessarily imply that a person will have Alzheimer's.  In fact, most people have neurofibrillary tangles, to one degree or another, much, much earlier in life than Alzheimer's would be seen.  This brings us back to the locus coeruleus, because this is often the first area where an excess of these tau proteins and neurofibrillary tangles can start to be seen within the brain.  Most people have some indication of tau pathology in their locus coeruleus by early adulthood, by a person's mid 20s.  But like I said, it's not a one-way ticket to Alzheimer's just because this is happening.  Alzheimer's increasingly seems to be a multivariate disease or syndrome, not something where there's exactly one cause or certainly exactly one cure.  But in the case of the locus coeruleus, the actual neurotransmitter, norepinephrine, that it secretes, seems like it might be helpful in actually preventing Alzheimer's symptoms.  Studies conducted with rats and mice have shown that norepinephrine helps to protect neurons from factors that can accelerate Alzheimer's disease, such as inflammation and excessive stimulation from other neurotransmitters. 

So, how do you get more norepinephrine?  That is something you do actually have some control over, because norepinephrine is released when someone engages in a mentally challenging activity.  That could be trying to do a really hard crossword puzzle, trying to learn a new language, trying to bake a 30-minute cake in 20 minutes--pretty much anything challenging that you can set your mind to, but the point is setting your mind to something.  Says Mather, "Education and engaging careers produce late-life cognitive reserve, or effective brain performance, despite encroaching pathology.  Activation of the locus coeruleus norepinephrine system by novelty and mental challenge throughout one's life may contribute to cognitive reserve."  So this is not a direct cause and effect; very few things seem to be direct cause and effect findings when it comes to Alzheimer's.  But the locus coeruleus is interesting because it's a bit of a "canary in a coal mine."  It has long, unmyelinated axons; it gets a lot of exposure to blood flow, and thus a lot of exposure to toxins within the body.  But because of its secretion of norepinephrine and norepinephrine neuroprotective properties, it's also a part of the brain that could be used as protection against Alzheimer's disease. 

— Main Interview --

Jesse: So, Alpha-GPC you may know better by its full name, which is Alpha-glycerophosphocholine.  Okay, that's probably not true, you probably don't know it by that name, but that's technically what it is.  The most important part of that name so far as we're concerned is the suffix, -choline, because Alpha-GPC is a precursor to acetylcholine, a neurotransmitter and neuromodulator within the brain, and also within the general nervous system.  I've heard it said that acetylcholine is the primary neurotransmitter, the most important neurotransmitter.  I'm not sure if it's really fair to think of neurotransmitters that way, it's kind of like saying what's the most important part of a car.  It's probably not the floor mats, but there's any number of parts that if you took it away, the car wouldn't drive anymore.  So, picking your favorite neurotransmitter is probably a fool's gambit, but nobody can say that acetylcholine is not an important one.  So Alpha-GPC is a naturally-occurring compound, but it's also something that we can supplement and make absolutely sure that our body has the coline that it needs in a raw form that can become acetylcholine down the road. 

Now in this interview, I'm going to be speaking with Scott Hagerman.  He's the president of Chemi Nutra, which is an American company, a subsidiary of an Italian company, and they're one of the primary manufacturers of both Alpha-GPC and phosphatidylserine.  We had a phosphatidylserine episode some time ago, probably over a year ago.  But in this one, we're gonna be focusing on Alpha-GPC, which we haven't really talked about before.  Scott Hagerman would be the first to tell you that he is not entirely unbiased when it comes to Alpha-GPC--he is the president of a company that sells the stuff.  So, a little different than some of the academic researchers that we talk to on a lot of episodes, but that is not to say that he does not know Alpha-GPC inside and out.  In fact, his company does finance a lot of research into Alpha-GPC and other compounds that they work with.  So, lots to be said.  Let's move into the interview with Scott Hagerman. 

--

Hagerman: I guess from the time I was maybe 15, I always had an interest in health and fitness.  I've always been very active physically.  I'm a certified trainer, I have a nutrition undergraduate degree.  Instead of going to graduate school, I decided to get an MBA, and that has been helpful in my career path.  But nevertheless, I've always had an interest in human nutrition.  Consequently here, one of our main objectives here at the company is to investigate the health benefits of our nutritional supplement ingredients.  So, we almost have research studies going every month of the year here, and have for the 16 years that this business has been here.  I don't know if everyone knows, we are a wholly-owned business unit of an Italian pharmaceutical company called ItalFarmaCo S. p. A, in Milan, Italy, they were founded in 1938.  So we're a privately-held pharma company that manufactures and distributes finished products. 

We're mostly invested these days in some really interesting areas--oncology and peptides, which are two blooming areas.  In that regard then, we have all of the resource capability of our laboratory and our QC people, our research, our doctor group and all that, over in Italy.  So we have a presence around the world; we have offices and plants in Malta and Brazil, in Russia, Spain, France.  A daughter company of ours here that I actually manage is Kemmy Pharma, so we're involved here in filing new drug applications with the FDA, and then when we get approval first, which will be probably 2017, we'll launch our own finished products under the Kemmy Pharma name as opposed to the ItalFarmaCo brand name.  This launches me into sort of how we got into this business, and that is in 1992 we foresaw a need for a brain nutrient, phosphatidylserine, so we were the pioneers in developing the methodology to manufacture that.  We have essentially all of the IP, all the patents that relate to the manufacturing, and we have several use patents.  In fact, everything we have is patented. 

Jesse: Now, phosphatidylserine, if I'm remembering this right, originally we got it from cow brains and then that quickly went out of vogue. 

Hagerman: Back in the '80s, when it became prominent, it was extracted from bovine cortex, from cow brain.  Starting in probably 1989-1991, it became a big deal, this awareness of bovine spongiform encephalopathy. 

Jesse: Mad Cow Disease, yeah. 

Hagerman: In fact, we had a researcher over in Italy that used to work in that field.  Some call it prion research, and yeah, Mad Cow Disease.  So, way back, and this goes back to the early '90s, we realized that and then we used our technology to make this from a natural plant source, so that's the route we took.  We brought it to market and we are still, to this day, the most prominent and primary manufacturers and researchers of phosphatidylserine.  And at this point, there have been hundreds and hundreds of studies, and all of the compounds of GRAS have been safely used. 

Jesse: And GRAS, that term, just in case anybody's not familiar, that's GRAS, Generally Recognized As Safe.  Tell me about your approach to research within your company.  When most people are thinking about academic research into compounds like this, we think of it as taking place in a university or the National Institute of Health or some other sort of non-business non-profit-making body.  How are things different or how are they the same?  Can you kind of compare/contrast how things go in a corporate vs.  an academic research world? 

Hagerman: It's interesting, in this day and age it's really incumbent on the ingredient companies to do the research.  So when we go to big companies, everybody asks for the ingredient and then they come to us and say, "But we need, before we buy it and in order to make health claims, we have to have the substantiation," that is usually more than one published paper, "showing evidence that this ingredient works."  And what's interesting from our standpoint, we do that for everything we have, we do that on an ongoing basis, so we do all that, we make the investment, and then we spend a lot of money on patent filing and then on side things that relate to the safety--that's toxicology studies and publications of results and things like that.  So, all of this thing is pretty big and nobody sees it, it's the tip of the iceberg story.  They buy the ingredient, but they really want the research.  And since I got into this business, I used to work in the pharma field, I worked for Pfizer for ten years and then I cut my teeth starting in 1992, when I got into nutrition.  Back then and since then, and that's more than 20 years, there has been increasing need and importance for substantiation.  On our side, we need it so that when we file safety, either GRAS or new dietary ingredient petition approval with the FDA, we have to have all that stuff anyway.  So we do it, and we do it because we're big enough and we have the resources. 

In terms of research, it gets expensive.  I mean, we have a research budget here.  Over in Italy, you can imagine what our research budget is there--it's a hundred times what ours is because they're doing things daily.  So, we invest in studies all the time.  We're working on some NIH things.  We're working on some military things--for example, combatants out in the field, for memory improvement, for managing stress.  In the main, what we do is we invest in studies and we gather evidence, we look at dose response, we look at pharmacokinetics, which is important, looking at bioavailability.  So we're trying to cover things from sort of the mechanistic standpoint, how it works, to the dose response standpoint, and all the while we're looking at outcomes.  It can be anything from increasing muscle mass, to decreasing fat mass, to improving a lot of different types of memory outcomes.  There are all kinds of these tests that are designed to look at memory and recall and learning and all these factors.  And in the old days, quite frankly, back when PS first came to market in the late '80s and early '90s, literally in Italy there was a bus that went around from city to city and enrolled people, and they would just go from city to city with their laboratory setup and visit the subjects and take measurements and provide the supplements and things like that.  So, that's the way it was done.  So compared to today, you can take subjects at home and they can log into a computer program, they can snap pictures of their food intake with their iPhones and send them in for data collection.  So, everything has changed with the advance of technology. 

Jesse: Yeah, absolutely.  So, let's switch gears and talk about Alpha-GPC.  Along with phosphatidylserine, this is one of the two main compounds that your company is really involved with.  What are some of the highlights of this compound?  What made this the choice? 

Hagerman: Yeah, Alpha Glycerylphosphorylcholine--and this will sound biased--but I think, based on the evidence, appears to be probably the most significant brain nutrient, and it possesses other health-benefiting qualities that I can talk about in a minute.  But Alpha-GPC is a normal component found in the body.  So when you ingest phospholipids--if you have three eggs for breakfast, you will have an intake of phospholipids, phospholipids look like triglycerides but they have a head group.  So the bottom line is if you eat three eggs, you're gonna form phosphatidylcholine, you'll have a little bit of phosphatidylserine, a little bit of phosphatidylethanolamine, a little bit of phosphatidylinositol, and those four make up the primary phospholipids found in nature, whether they're from animal tissue or vegetable tissue.  Alpha-GPC is real similar to phosphatidylcholine, but it doesn't have the fatty acids on the first and second position.  So it ends in a choline head group, so on a weight/weight basis, it's predominantly choline, 42% choline.  And the interesting thing is it becomes brain-bound.  So this choline, through a phospholipid, crosses the blood-brain barrier, whereas choline salts, those typically are known as choline chloride, choline bitartrate are the two classic examples that you see in foods and pet foods, they do not cross the blood-brain barrier, and there's some published papers indicating that.  So, systemically those synthetic choline salts are okay for systemic choline.  But again, in terms of the brain, the choline can really only come from phospholipid-like compounds, because then it's carried through the membrane into the brain structure itself.  So, Alpha-GPC has been the subject of, again, hundreds and hundreds of studies.  Our parent company, in fact, sells it as an Alzheimer's drug, and they sell it for dementia, stroke, and coma. 

Jesse: Is that to say that it's actually like a prescription drug for Alzheimer's patients?  It would be a prescribed thing rather than over-the-counter? 

Hagerman: Yeah, and depending on the country, for some countries it is a prescription drugs from doctors, for some it's an OTC.  There's a difference in the far east, there's a difference in the Baltic states, and Russia.  So again, we've been marketing Alpha-GPC as an injectable and an oral preparation for Alzheimer's disease, dementia, stroke, coma, age-related memory loss, all of those types of indications, for more than 20 years.  In fact, the research that has been put forth of late shows that Alpha-GPC works far better than donepezil, trade name aricept, which is an acetylcholinesterase inhibitor. 

Jesse: The phospholipids help it cross the blood-brain barrier, but once it's in there, what's it actually doing?  What's the mechanism of action once it's in the brain? 

Hagerman: So the mode of action for Alpha-GPC is pretty basic.  What it does, it boosts acetylcholine in the synaptic cleft.  So the cleft is that space between neurons where compounds exist, and they're involved in the transmission of electrical signals from neurons across the dendrites, these little finger-like projections that stick out.  So, acetylcholine is the name of the game.  So as you get older or under stress or under certain conditions, we don't generate acetylcholine optimally.  So there are lots of conditions, and I don't really intend to talk about medical uses, but the bottom line is if acetylcholine is not at its maximum level, then there will be a compromise in cell-to-cell communication, and therefore learning and memory and recall and all those things are negatively impacted. 

Alpha-GPC is, again, in summary, a real basic compound.  It's a biosynthetic compound from foodstuffs, from oilseeds primarily, from animal tissue.  But again, as a starting block material in your gut, it is transformed into phosphatidylcholine and other compounds.  So, the body really doesn't see a lot of it, and the different tissues and the different organs have different needs for it.  So things are biosynthesized according to needs of tissue and needs of organs.  So the brain is very high in phospholipids, very high in a dry weight basis.  Alpha-GPC then, again, is a real strong component that boosts acetylcholine, and now the story becomes it's not only brain-bound, it's involved in all of the synaptic activities around the body.  So the things of our interest and focus in the last years have been looking at explosive power output, and that means that the motor unit--same thing as a neuron in your brain, it's the same kind of neuron that's at the end of a long axon at the point of engaging muscle fiber.  All your muscles have these neurons, they're called motor units, that activate contraction of muscle fibers, so they're really key to agility and explosive power and all these things--they're all related.  Just like in your brain, if you have an ample supply of acetylcholine at the motor unit, you'll more optimally fire contractile muscle.  And again, the whole activity has to do with an impulse in your brain to fire down your spinal column to the motor unit to engage the muscle tissue from the release of calcium and the sarcolemma and that whole thing.  So it's explosive power and thinking and all these things, they're all interrelated. 

Jesse: What have the studies shown for the time of onset from the time that somebody takes exogenous Alpha-GPC, for that to actually have results, and then how long did those results last before you dropped down to baseline? 

Hagerman: Well, the studies that have been published show that it takes about 30 minutes, I think one study showed maybe as little as 20.  But 20 to 40 minutes, which would be really pretty fast.  If you look at the pharmacokinetics of caffeine, caffeine will hit the bloodstream pretty quickly, like 20 minutes. 

Jesse: Yeah, I think for almost anything taken orally, 20 minutes is about as fast as you're ever gonna get. 

Hagerman: 20-40 minutes is what's seen in all the studies, and the duration is several hours.  Now for a more advanced answer to that, unfortunately I could only give you animal data.  So we have radiolabeled studies done with Alpha-GPC, and these are done in rats, of course--you can't administer radioactive things to people.  We take Alpha-GPC and add a radiation agent, administer that usually through tail-veining to a rat, and then we look at its onset in the different tissues.  I did this kind of work at the university for a couple of years, and that's what you do.  You inject this radioisotope, and it's short-lived, and then you sacrifice the animal and you extract the spleen and the lung and the kidneys and muscle tissue and things like that, and then you do a scintillation assay.  You look at the activity in the different tissues and you can measure how quickly it was taken up.  But you don't do that in people.  There are different things that can be done in people, looking at positron emission tomography that are sometimes done for cognition reasons, and there's actually some of that which was done on phosphatidylserine, but we haven't done that on GPC--we're actually talking about that.  So, classically we've looked at studies where we do different kinds of outcomes on learning and memory and recall.  These more exotic-type things would only be done in the drug world. 

Jesse: It's interesting, because it's a prescription drug, at least in parts of Europe, it makes me wonder, is there a point at which it's dangerous, like an overdose potential?  What would taking too much Alpha-GPC look like? 

Hagerman: Of course, and we shared this when we submitted our GRAS dossier to the FDA in 2014.  We have full toxicology data, and that encompasses the spectrum of dosages that are used.  So sort of minimally, we see dosages of maybe as little as 25mg, but customarily in the dietary supplement arena or sports nutrition arena, we'll see a use of maybe 200mg.  And the clinical use--if you or I or one of our loved ones was diagnosed clinically with Alzheimer's disease or dementia, the dose that they would be given would be somewhere between 1,000mg and 1,200mg a day.  And as an aside to that of course, we have pretty long use longitudinal studies looking at the administration of high dosages of 1,000mg to 1,200mg of Alpha-GPC in these clinically-diagnosed patient populations, and we have seen less than I think 1% adverse events.  Adverse events typically would be upset stomach.  And again, this is not a traditional drug in the sense that it's a synthetic compound that somebody made.  These are fully natural, highly purified compounds, just like what we sell in the nutritional arena.  They're orthomolecular--fancy word again for they're found in your diet, they're a normal biological compound in the body, it's a base stock hydrolases compound from normal phospholipid and lipid ingestion.  So you ingest this, you produce this, and that's what makes it pretty unique.  It's not a drug in the drug sense, it's foreign to the body; it's a part of the normal body chemistry. 

Jesse: Right, so it shouldn't be surprising that we've got pretty decent tolerance to it, even if the levels were a little high.  What do you see in this adverse events? 

Hagerman: I mean, there are only a couple that you'd ever see mostly in any kind of nutrient.  That'd be a stomach ache, regurgitation, or a headache.  And then as you get down the GI tract, it could be loose bowels and things like that, but those would normally be bacterial.  Nutrients are really pretty limited relative to drugs, which really do have, a lot of times, some pretty serious contraindications. 

Jesse: Would it be worth paying attention to what time of day a person takes it?  Is it something that, because it tends to be a stimulant in the sense that acetylcholine is generally an excitatory neurotransmitter, is it going to mess with your sleep if you take it late in the day, anything like that? 

Hagerman: There was actually a paper published some years ago, because somebody had that thought, that maybe because it boosts acetylcholine and kind of wakes up the whole neural system, that maybe it would affect sleep quality.  So the paper that was published showed that it didn't have any impact on it.  We used to work with a guy, he was the head of research for a phospholipid company over in Hamburg, Germany.  I remember him telling me this about 15 or 20 years ago, that when he took Alpha-GPC sometimes, he would have vivid dreams.  We've heard a couple people say that, but we can't really corroborate that.  But we do know, as I said, it does not negatively affect sleep quality. 

Jesse: Are there any studies on Alpha-GPC that you haven't done yet that you really want to do, that you're still wondering what it does, what it can do? 

Hagerman: Yeah, we've explored some interesting areas, and one of those has to do with human growth hormone.  So there are studies in the public domain, well before we commercially launched our product more than 12 years ago, there's a mechanism that's well identified.  If you take Alpha-GPC orally, you boost human growth hormone, especially when you are engaged in exercise that involves large muscle.  As you involve large muscle, there's naturally a little increase in anabolic hormones, that family of hormones that include human growth hormone, testosterone, insulin, and IGF1.  So, if you exercise, probably if you go for a walk at night you're going to get a little spurt in growth hormone.  When you sleep, you wake up in the morning with the highest titer, the highest level of growth hormone, and the fact that this growth hormone thing has to do with aging and is an anti-aging therapy, and people take it exogenously with a needle, there's a whole practice based on that. . .  Because you get older, it's like all hormones, there's a change in your body as you get older and it brings in effects on skin elasticity, and sleep quality, sexual activity, muscle mass, and all that kind of stuff.  So to that end, we have published some papers over the years looking at that.  The reality, in the end, is that the best effect is it'll raise growth hormone a little bit.  And this is beneficial to men and women, it would never be detrimental.  It doesn't raise it like what a drug would, and the benefit is sort of overshadowed by the fact that this titer, fancy word for this level that goes up, only stays up for a couple of hours and it falls down, and that's just the effect of growth hormone, there's no way around it.  So we have products out there in the marketplace, from finished product companies utilizing this in hormone normalization products and things like that. 

The other area that has been more interesting for us in sports applications and applications, in both aging people and in active people, is its effect on the motor unit and activity on agility, jumping, and running, endurance activities, explosive power output. . .  So we've conducted a number of studies looking at that, and then more recently we've been looking at the Alpha-GPC effects in comparison to caffeine.  So, caffeine is kind of interesting because I guess you'd call it a neurological agent, we all know what caffeine does, and there's a lot of issue out there, concerns for use.  For example, if you want to go to the gym and exercise at 9 o'clock and you don't want to take a lot of caffeine, even though you want it to boost your performance, but then you'll be up all night.  We've been exploring this and we actually filed a patent, and the claims basically say that Alpha-GPC provides superior physiological benefit than caffeine, so therefore it can be used to either augment it, or replace it, or reduce it, all those different things. 

Jesse: Yeah, I think a pretty different mechanism of action, so you could do both. 

Hagerman: Caffeine has been studied in some brain activity studies, and I think there's a little boost, and there are hundreds of studies on caffeine dosages, and caffeine dosages range somewhere between 60mg a dose and 900mg a dose in the studies.  So, that's an area that's pretty interesting to us. 

Jesse: Back to the brain for a minute.  You mentioned that you used this as an Alzheimer's therapeutic.  What other studies have you done looking at brain health or cognition? 

Hagerman: Well, there are so many studies that have been done on the outside and by ItalFarmaco, our parent company, that were done 10-15 years ago.  There's so much evidence for Alpha-GPC that, to be honest, there's no reason for us to invest even a dime in additional studies on cognition, because it's all there.  But from the performance standpoint, from the dose standpoint, it goes all the way up to clinical manifestations--and I might add this: we're exploring and in discussion with some bonafide medical food companies, looking specifically at them preparing and marketing finished products for Alzheimer's disease and dementia.  So we're just around the corner, literally, to where a couple of companies launch medical foods that utilize Alpha-GPC as its keynote ingredient.  And without going into a long discussion of that, there's some difficult and challenging criteria that have to be met with respect to FDA and use in medical foods.  One of the has to be that it's GRAS, because it's in the food classification.  So in terms of FDA positioning, the best and highest level you can reach is full GRAS.  That means submission of a dossier to FDA, they review it, they assign it a GRN number, they publish it on their website, and they send back what's called a No Questions Letter, which means they've reviewed it and they're satisfied with it, it's a home run.  And that would allow for use in foods and medical foods, functional foods.  We can put this in chocolate, we can put this in beverages--and, in fact, we do.  We have Alpha-GPC in a number of beverages that are sold commercially for brain health and mental performance.  Human performance we think is a real area, the real emphasis--mental and physical performance--because they're so directly linked. 

--

Jesse: So, thank you so very much to Scott Hagerman for taking the time for that conversation.  I feel like we’re long overdue for an acetylcholine Know Your Neurotransmitters episode, that’s something we probably should have gotten to a long time ago.  We’ll definitely try to bring up the rear and get you that before long.  Choline sources, for what it’s worth, can also be found in natural foods; eggs are probably the best-known example.  One other thing worth mentioning if you’re the type that mixes up your own compounds, gets things in powder form: Alpha-GPC loves water, it will actually pull it out of the air; powder that’s sitting around will turn into like a gel or a liquid.  It doesn’t actually degrade the Alpha-GPC chemically, but it will obviously change how much it weighs.  So if you’re weighing Alpha-GPC after it’s gotten wet, you might get the dosage wrong.  So people that do that like to store it in a vacuum-sealed bag.  Sort of a pro-tip for the ultra supplement geeks out there.  Probably not relevant to most people, but now ya know.  That is all for Alpha-GPC for right now.  Let’s move on to the Ruthless Listener-Retention Gimmick. 

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— Ruthless Listener-Retention Gimmick --

Jesse: So back in episode #134, we talked about rapamycin with Professor Matt Kaeberlein from the University of Washington.  The study that we talked about most was the dog longevity project.  But he doesn’t stick to dogs, he does mouse studies as well, and he recently published findings from a mouse longevity study, again, dealing with rapamycin, and some really interesting, really promising findings.  There are some caveats, it is not all sunshine and butterflies.  But the gist of this is that they did a 90-day intervention with rapamycin on elderly mice.  So for three months, the mice received rapamycin.  This wasn’t from the time that they were mouse pups, they were actually 20-months old at the time of this intervention, which is the equivalent of about 60-years-old if you were a human.  Now, the mice who received this treatment, they went on to have a 60% longer survival time vs.  their untreated peers in the control group.  So, a pretty big result given that this was applied late in life and was also a short-term intervention. 

Said Kaeberlein, "It’s quite striking that a short-term rapamycin treatment had such a lasting impact on health and survival after the treatment was stopped."  The longest-lived mouse in the study who was one of the rapamycin-receiving mice, he lived for 1,400 days, which is the equivalent of a human living to 140-years-old.  Now, there were some asterisks on rapamycin’s performance.  For one thing, interestingly, even though rapamycin was helpful in terms of longevity for both male and female mice, the male mice lived substantially longer than the female mice after the rapamycin treatment.  So it helped them both, but it helped the male mice more.  The female mice receiving rapamycin also proved to be more susceptible to certain types of cancer, and in both male and female mice they saw changes in the microbiomes of those mice, the gut flora little beasties that live in the digestive tract.  Those changes didn’t necessarily seem to be negative or positive, but they did see a proliferation of certain types of bacteria, the kind of thing that makes the scientists want to do more studies rather than say, "Hey, let’s go ahead and move to a human trial." 

So in summary, rapamycin trial short-term intervention on aged mice: the mice live a lot longer, a little bit more cancer, more questions to be asked, more studies to be done, but nevertheless, very promising findings. 

Written by Hannah Sabih
Hannah believes there's nothing 8 hours of sleep and some kale can't cure (yes, she's from California). She's an avid runner, reader, and traveler, who brings you the latest and greatest in neuroscience via our social media channels.
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