Sam Henderson – Ketones, Alzheimer’s and Nerve Protection

LISTEN (45 minutes)

 

(EDITOR’S NOTE:  This conversation is with Sam Henderson of Accera  in Broomfield, Colorado.  We did this interview a week or so before the Wall Street Journal published a story about Axona, which is Accera’s “milkshake” for mild cognitive impairment.   The “milkshake” comes in a small pouch.  You open it up and it’s filled with cream-colored granules that you mix with something, such as water, and it makes a sort of milkish-thickness drink that, due to a tiny bit of sugar and some artificial sweeteners and flavors, tastes mildly sweet, and while it’s probably not something you’d order on a night out with a friend just for the taste of it, it’s not so bad.  The key in this conversation is . . . are we really talking about Axona, the milkshake, which helps the body produce ketones despite eating carbs?  Or are we talking about why ketones may be part of neuro-protection through a diet, for instance.  Sam Henderson says in many ways that a ketogenic diet is more effective than eating carbs and taking a ketone-producing supplement.  As for the rest . . . well, you’ll see.)

Sam Henderson, it was 10 years ago, maybe 15, that you decided you wanted to find ways to slow down or reverse Alzheimer’s.

SAM HENDERSON That’s correct, when my mom was diagnosed with Alzheimer’s disease, I made that my new scientific line of investigation.

plaques_and_tangles_border

The medical illustration is provided courtesy of Alzheimer's Disease Research, a program of BrightFocus Foundation.

The focus that you gave to this was different than most other researchers, though. It went a different direction than clearing out the sticky, tarry A beta and tau-related plaques in the brain that many researchers assumed were the cause of Alzheimer’s.

SAM HENDERSON Yeah, you know, I looked at the current data which was out at the time, which was focused on A beta and tau, and I looked at the stuff that was being done at the company I was working at at the time, and it was too long-term for me. My mom was diagnosed then, and all these other treatments were five, ten years out. I thought we needed something sooner and faster.

At that time the focus was on trying to melt out the gummy tars in the brain with the thought that that would make Alzheimer’s go away.

SAM HENDERSON

Cerebral Edema

Cerebral Edema

Yeah, that’s still pretty much the focus. We’ve had several really big trials recently. There’s one drug developed by Pfizer and Elan called bapineuzumab, which is a humanized antibody to the sticky plaques that accumulate in your brain. They’ve been having all sorts of trouble with that trial, unfortunately. What it is, it’s an infused antibody, so you have to sit in the doctor’s office and they infuse you with the antibody, it binds to the protein and then clears it out of your blood. Unfortunately, some of the patients, particularly the ones who carry the genetic risk factor for Alzheimer’s disease, develop really bad cerebral edema, they get swelling in the brain, so they’ve had to back off on the high dose in those patients.

For well over a decade, a small band of maverick researchers have warned that dissolving out those tarry plaques in the brain of a dementia patient is a bad idea. They’ve said that those plaques may be bandaids to deal with the damage that’s in there, and if you melt them out, you could cause more bleeding and the release of toxins into healthy sections of the brain. And you could get things like cerebral hemorrhages.

SAM HENDERSON – There’s a lot of people questioning now the whole A beta hypothesis for Alzheimer’s disease. But I think the big bapineuzumab trial and Eli Lilly has another monoclonal antibody, and I think BMS, Bristol Myers Squibb, has one as well. I think once they do these trials, if they really don’t get any cognitive improvements, then that’ll be a good piece of data to have to move the field somewhere else.

And all this time you’ve been moving in a different direction from that idea of melting the plaques with drugs. You’ve been thinking, what can we do to nourish the nerves so they function better?

SAM HENDERSON – Right. The hypothesis that we work on is that there’s this well-known problem that occurs in Alzheimer’s disease in that your brain has difficulty metabolizing sugar. Sugar’s the main source of energy for your brain.

Let’s back up. Does sugar have to be the main source of energy for the brain, or is it the one that most people in modern countries are habituated to using? That is, their brains are accustomed to using sugar as the main food but the brain could be adapted to using something else?

SAM HENDERSON – Your brain doesn’t really use fats, like most of the rest of your body does. It pretty much wants to run on glucose all the time. There’s only one other fuel that it can use efficiently, and that are what are called ketone bodies. And as you mentioned (before we started recording), in modern Western society with diets very rich in carbohydrates, you almost never enter ketosis. That’s considered a disease state, almost.

Perhaps we could say that being in a state of nutritional ketosis is so unknown among most traditional healthcare practitioners that they’re scared of it?

SAM HENDERSON Oh, yeah, absolutely. I gave a talk recently, and one of the physicians got up and said, “I spend most of my time trying to keep my patients out of ketosis. Now you’re telling me to put them into ketosis? It doesn’t make any sense.” There’s been a very long bias in the medical literature against ketosis.

That literature focuses on the truly dangerous condition of ketoacidosis, where a diabetic’s blood sugars are high at the same time that their ketones start running high. But when a person adapts to fat-burning by eating a low-carb diet or a very reduced calorie diet, with their blood sugars running more in the normal range, and THEN they’re producing ketones, that’s a different situation. And if we look back at traditional cultures, there are a number of those where a whole culture of people, for thousands of years or maybe tens of thousands or more, maintained bodies that were in ketosis most of the time because they didn’t eat carbohydrates. You can probably name some of those cultures.

SAM HENDERSON Absolutely, like the Inuits. The farther north you go in latitude, the less plant matter and carbohydrates people eat in their diets. Inuits live close to the North Pole, where there’s virtually no carbohydrate sources there to eat, so they eat almost entirely fat and protein. And mostly fat. SAM HENDERSON Mostly fat. The Plains Indians, in what’s now the U.S., the warriors especially really preferred to eat mostly fat and meat, a little bit, and as little of what they considered, “that wimpy” carbohydrate as they could.

SAM HENDERSON There’s a really good book out, Good Calories, Bad Calories, by Gary Taubes. He points out that in the 1800s, it was very well known that carbohydrates made you fat, which is common knowledge. But then we went through this big shift where we went to vilify fats and promote carbohydrates in people’s diets, and now people eat 55%, 60% of their core intake from carbohydrates, which is probably very evolutionarily discordant. For most people, practically everyone, that’s not a good diet.

You’ve looked at the popular literature and know some of the history of how other people ate, but mostly you’ve looked at this as a scientist, and a scientist whose mom had Alzheimer’s, and you wished that she could have been healthier. And you look at other people and you wish they could be healthier. You’re interested in this stuff called ketones that the brain can use that our bodies manufacture from fat, and something all of us can make. Tell us more about that.

SAM HENDERSON Ketones are a natural part of your physiology. For instance, when you wake up in the morning, your ketone levels are slightly elevated because you fasted overnight.

Meaning, they become elevated in your bloodstream because you didn’t eat anything overnight?

SAM HENDERSON Right. Your blood glucose gets a little low, and your body starts to burn its fat to make ketone bodies. The literature about how this works goes back to the 1960s, where they did a really interesting experiment where they took a bunch of obese people and they starved them. They didn’t eat anything for five weeks, literally all they had was water and a vitamin and some salt. In that paper. The researcher who did this shows that there’s this huge spike of ketone bodies that occurs, and so he talks about—and particularly these ketone bodies are used to fuel your brain, because your brain needs a lot of energy. Your body can make glucose, sugar, so he raised the question, why doesn’t it just make more sugar to fuel your brain, instead of using these ketone bodies, which everybody thought were bad?

Let’s slow down for just a second here and let people take that in. If we aren’t eating anything, our bodies can choose to make either sugar from the tissue in our bodies, or it can make fat from the stored fats in our bodies, including ketones that our brain can use. In other words, if you stop eating, your body can make either one, and you say that in this situation it chooses to make which one?

SAM HENDERSON It’ll make the ketone bodies. He explains in this paper why that occurs. The major source for glucose or sugar to be made in your body is amino acids, proteins. When you’ve run out of fuel for an extended period of time, your body will start to break down its major source of proteins, which is your muscles. So you can imagine, if you’re starving and you start breaking down your muscles, this is very bad, evolutionarily. You can’t hunt, you can’t gather, you can’t find food if you’re weak and tired. And your body doesn’t really carry that much stored energy as protein anyway. On the other hand, if you think about it, a typical person carries tens of thousands of calories around as fat.

Even if you’re skinny?

SAM HENDERSON Even if you’re pretty skinny. And unfortunately in America, with the obesity epidemic, there are people who have literally hundreds of thousands of calories that they’re carrying around as fat.

For some reason, the metabolism of a person who’s overweight can get locked out from reaching into that store of fat. But if somebody stops eating, the lock on the metabolism gets released, and it gets easier to reach the energy stored in fat?

SAM HENDERSON Right. It makes a lot of sense if you think about it, because your body will then start to tap that very abundant source of energy in fat, to provide these ketone bodies, which can be used by lots of tissues in your body, particularly your brain. The thought I had over 10 years ago now was that if in Alzheimer’s you’re having difficulty metabolizing glucose, maybe we can provide the brain with a ketone body, which is a normal fuel for your brain anyhow.

If your body will make it if a person just stops eating, why not just have Alzheimer’s patients just stop eating so they make their own ketones?

SAM HENDERSON [laughs] You could do that, but it’s probably not a good way to go. You could also try these ketogenic diets, high-fat, low-protein diets, low carbohydrate as well, because remember, you’ll make glucose from the proteins, so in a true ketogenic diet, you eat very low amounts of protein. You’re basically eating very, very large amounts of fat.

In a ketogenic diet, a person could eat that their whole lives? The Eskimo up in the Arctic Circle, this is how they lived, and this is how the Maasai warriors lived and how the Plains Indian lived, on that kind of diet. It’s not like it’s a starvation diet, it’s just a certain way to eat.

SAM HENDERSON Yeah. There was a paper that came out this year showing that a ketogenic diet improves cognitive performance in people with what’s called “mild cognitive impairment,” which is thought to be a prodromo syndrome of Alzheimer’s disease.

What does “prodromo” mean?

SAM HENDERSON A precursor syndrome. You’re going to start with MCI (Mild Cognitive Impairment) and progress into Alzheimer’s disease eventually. So I think the field is coming around to this idea that ketone bodies are not a bad thing and that it makes sense to provide your body with ketone bodies. These cultures that practice fasting, there’s probably a reason they developed that. They knew intuitively that it was good for you. But having said all that, it’s very difficult to fast, and it’s very difficult to do a true ketogenic diet, because carbohydrates are everywhere.

You say it’s very difficult to fast, but Sam Henderson, you or I could just go, “Hey, we’re going to stop eating for a couple of days and see what happens.” But then, you’re probably healthy enough to do that, feel a little tired and sleepy, but you could probably get everything else you want done, even while you’re fasting. What about somebody who is frail and is already having trouble with their brain and they’re struggling? What would if you say to that person, “Let’s just have you stop eating for a couple of days”?

SAM HENDERSON Once that disease state has set in, it’s probably going to be very difficult to do that. For example, in Alzheimer’s disease, there’s a very well-known shift in food preference. People with Alzheimer’s disease tend to like very, very sweet foods. One hypothesis is that’s the brain saying, “Look, we’re starving up here, we need some sugar, we need something to eat. So quick go out and get some Pop-Tarts or donuts or whatever.” For an Alzheimer’s to not eat or eat a ketogenic diet is going to be a compliance challenge.

Meaning that they’ll be suffering? They’ll be unhappy?

SAM HENDERSON They’ll be very unhappy.

Is it like telling a cocaine addict or an alcoholic, “Look, it’s time to stop having cocaine or alcohol”? Would it be better just to stop?

SAM HENDERSON I think any of your listeners who try to do an Atkins diet, you know that after a while of not eating carbohydrates, after a week, you really get that craving. You really want to go out and eat a donut. Serotonin levels go up when you eat carbohydrates, so there’s probably an addictive quality to it.

With quitting tobacco campaigns, quitline counselors generally tell people that about 10 days into quitting, you’re really going to miss it.

SAM HENDERSON And I think that’s very true of carbohydrates as well. You’re definitely going to crave those.

Well, one choice people have is to get through that period of intense craving and get to the other side. We all know people who quit smoking, and they don’t crave cigarettes any more, meaning they just keep them away so they don’t have the craving again.

SAM HENDERSON Absolutely. Once you get over that hump, that phase where you really, really want it, you’re probably OK, for the most part, unless you start falling off that wagon again, which is very, very easy to do in our society when it comes to dieting.

Despite the fact you have a product that provides ketones to people who have not switched into fat-burning mode, you’re acknowledging that eating a low-carb, adequate protein, high fat diet could be once choice that people could make?

SAM HENDERSON It’s the preferred choice. If you can cut your carbohydrates down and do that for most of your life, it’ll probably greatly reduce a lot of disease state, type 2 diabetes, Alzheimer’s, lots of other conditions. If you can stick to that kind of diet, obviously I think that’s the way to go.

Just from a philosophical and personal standpoint, that’s what you say. But at the same time, you expect a lot of people would rather have their cake and their ketone bodies, too?

SAM HENDERSON Exactly. That’s the ideal condition you want. Eat anything you want but not develop those disease states. That’s where everyone would want to go.

And given the fact that a lot of people have such trouble making the shift away from carbohydrates even though carbohydrates are harming them, that’s where you thought of your product, to give people a way to take in ketone bodies without adapting their body to making them themselves.

SAM HENDERSON It’s very difficult to restrict carbohydrates, so could we find an ingredient or a compound that you could take that would induce ketosis while you were still eating carbohydrates in things in your diet. That was the genesis of the idea. What we use are these things called medium-chain triglycerides, which are fats that are very different from traditional long-chain triglyceride fats.

Is a medium chain triglyceride like fish oil?

SAM HENDERSON Fish oil is a long-chain triglyceride, but a long-chain triglyceride is basically any triglyceride that contains fatty acid chance over 14 carbons. Almost every fat that you eat is a long-chain triglyceride.

Is butter a long-chain triglyceride?

SAM HENDERSON Yes.

The fat in meat?

SAM HENDERSON Yes.

Olive oil?

SAM HENDERSON Yes.

Fish oil?

SAM HENDERSON Yes.

So it’s just anything that tastes fatty?

SAM HENDERSON Almost 98% of the fat you take in in your diet will be a long-chain triglyceride. The medium-chain triglycerides are somewhat difficult to come by in pure form.

EDITOR’S NOTE – Coconut Oil is one of the best natural sources of Medium Chain Triglycerides, even though it’s NOT the main source of fat in that oil.

Someone once told me that a medium- or short-chain triglyceride tastes like vinegar.

SAM HENDERSON If it’s a pure medium chain triglyceride and it has no pre-fatty acids in it, there’s no taste. It’s odorless, tasteless, colorless liquid.

Does it have a mouth feel of fat?

SAM HENDERSON Yeah, it’s got kind of a slippery oil-like feel to it.

Do you have some here in your office that is tasteable? Could anybody taste it? Could I buy it at a pharmacy or Wal-Mart?

SAM HENDERSON You can get it from some specialty nutrition places online, things like that. It’s not that hard to find.

Is it a stable product?

SAM HENDERSON They’re very stable, since they’re fully saturated fats, they do not get oxidized readily at all . They’re very, very stable.

What made you think that this would be a good line of product to start making for the sake of Alzheimer’s who don’t want to give up carbs? What was your thinking on how it could help them?

SAM HENDERSON The thought was that since their brains are having difficulty metabolizing sugar, glucose, is there another fuel that we can give them that maybe they’ll be able to metabolize easier and more efficiently? That fuel is these ketone bodies. The idea is that when you take in these medium-chain triglycerides, your body will oxidize those or metabolize those regardless of your metabolic state. For example, you can take in MCTs with a large amount of carbohydrate and your body will still metabolize them to produce ketone bodies.

I’m envisioning something where somebody takes in this product that makes it easier to make ketones and their body just pours it out again, it just comes out in the urine, in the feces, and it never gets processed. Do you have evidence that shows that the body will gladly take this in and use it for energy?

SAM HENDERSON There are studies that demonstrate this, where they take normal, healthy people and infuse them with ketone bodies and then follow their metabolism through the body. You can see when people do this, there’s several good studies from in the ’90s where they show that when you infuse people with one particular ketone called beta-hydroxybutyrate, you can see a big increase in the uptake of that compound into the brain and metabolism of that compound in the brain, with a concomitant reduction in glucose metabolism in the brain. This paper clearly shows that when you elevate ketones in circulation in your body, your brain sort of switches over to metabolizing the ketones instead of the glucose.

That’s an interesting study, but you’re not describing something where these people are starving or on a fast. Instead, they just got this special nutrient and the brain went, “Yahoo! This is what we’d rather have!”

SAM HENDERSON The benefits of the ketone body is, it’s very easily metabolized. It’s only a four-carbon molecule, so it can very readily be metabolized and enter the citric acid cycle in your mitochondria, unlike glucose, which is a fairly large molecule and has to go through the steps of glycolysis to be broken down.

There’s this little engine in your cells called the mitochondria. It’s a few steps for glucose, sugars, to be metabolized and burned inside that mitochondria or anywhere in the cell. But oil just kind of slips right in, and the mitochondria has a very easy time turning that into energy.

SAM HENDERSON There are only three steps before it becomes acetyl co-enzyme A compared to glucose, which is, I think, 12. So it’s much easier for your body to metabolize it than it is for a molecule of glucose.

And that’s why the brain might like it better?

SAM HENDERSON Yeah. It’s a very efficient fuel, because it’s basically a ready to go molecule for the mitochondria.

In a healthy person, does it reduce their cravings for sugar?

SAM HENDERSON There have been a number of studies looking at MCTs for things like satiety and weight loss. Some of them show that it will reduce the desire to eat food. But the caveat with these studies is that MCTs are a little difficult to digest.

Medium-chain triglycerides?

SAM HENDERSON When you take them in, there tends to be, especially if you take a large amount, some diarrhea and nausea and things like that from the rapid metabolism of the MCT.

So your bloodstream might say there’s a fuel inside the bloodstream to give to cells, but the digestive tract, just as a liquid to be taking in, is a little challenged by how to process it?

SAM HENDERSON Yeah, especially if you take the straight oil, it can be quite hard—just imagine taking any straight oil, it’d be a little hard to digest. So we spent a lot of time formulating it to make it easier to digest. We titrate people on the dose to get them acclimated to the fairly large does that we give them.

Would it make a good salad dressing?

SAM HENDERSON I don’t know. I’ve never tried that.

That would give some roughage to eat with the oil so that it might slow down the digestion enough to let the digestion take it in more.

SAM HENDERSON We typically recommend people take it with another fatty fat source. What you’re trying to do is give another fat to compete out the lipases that break down the MCT, so you don’t have quite as rapid a digestion of the MCT.

So lipase is a digestive enzyme in the gut, the stomach?

SAM HENDERSON Yeah, it’s mostly in your small intestine.

Is it in the duodenum?

SAM HENDERSON Yes.

The little pouch that’s just below the stomach. It breaks down fatty acids to their very simplest form, which is more like a vinegary kind of stuff. But you would rather have these medium-chain triglycerides be undigested when they hit the bloodstream?

SAM HENDERSON The lipases attack the triglyceride and cut off the fatty acids, and then for a medium-fatty acid, these little fats then go directly via the portal vein to your liver, which is a very different pathway than a long-chain fatty acid would take.

The medium- and short-chain fatty acids, this is kind of geeky, but let’s explain it. The big complicated ones, like butters and olive oils, they go into these kind of balls of fat that go into your lymph system?

SAM HENDERSON That’s correct. When you go to McDonald’s and eat a Big Mac that’s full of long-chain triglycerides and you eat some carbohydrate with it—well, it doesn’t matter if you have carbohydrate or not, the long-chain triglyceride, the lipases will attack that. They’ll cut off the fatty acids off that. Then the cells in your gut will reassemble it back as a triglyceride and then take that and make it into these big ball, big lipoprotein particles, and then dump that into your lymph system in your neck, which then enters into circulation.

It just kind of floats along, drifts through the lymph system, up to the vein in your neck, and then it goes whoosh! into your heart and on from there?

SAM HENDERSON These little protein particles people know as LDL and HDL.

You have these big things called chylomicrons?

SAM HENDERSON What you don’t want are these LDL particles floating around in your bloodstream, because that means you’re not breaking down the fats. You want the HLDs, the “good” cholesterol, people call it, which are basically the fat-depleted versions of these little protein particles.

This is a long and detailed explanation as to why there’s some thought that goes into what kind of fat you want people to eat. You want to have a fat that slips by this slow barge-like system of the lymph system, that’s small enough that the body goes, “We can just send this right to the liver.”

SAM HENDERSON So when a medium-chain triglyceride gets cleaved, those little medium-chain fatty acids are very soluble and they’re small, so they don’t get reesterified and reassembled back in the triglycerides and don’t get assembled in these lipoprotein particles. Instead, the medium-chain fatty acids go directly to ___, straight to the liver. And once they get to the liver, again, they’re not reesterified. The liver just says, “Oh, OK, here’s some medium-chain fatty acid, we’re just going to oxidize it. We’re just going to start metabolizing it regardless of anything in the diet. We’re just going to burn it.”

It says, “Oh, great! Here’s some of those good old medium-chain triglycerides. We don’t have to do anything to them. Let’s just send them right on because the body needs them.

SAM HENDERSON Right. It’s going to break them down no matter what.

And so your thought about eating a little bit of other kind of fat with your formulation is so that the lipases go after that and let the MCTs go through just like they are, because that’s the best way for the body to use them.

SAM HENDERSON The MCTs are metabolized very efficiently, so those medium-chain fatty acids are cut off very quickly. When you take in an large amount of the MCTs, you can get this large amount of medium-chain fatty acids in your duodenum, which can be for some people hard to tolerate. So if you can slow that digestion down a little bit, then you can reduce the adverse events you see with the MCTs. In our formulation we mix in some long-chain triglyceride, and we recommend people take it with a meal. It’s better if they take it with a fatty meal, a little bit of cheese, maybe, or something that can slow the digestion down a little bit.

In a way, it might be good to be adapted to a higher-fat diet anyway, if you’re taking this product?

SAM HENDERSON Oh, definitely, yeah. People have known for a long time on these ketogenic diets that they give to kids that if you slowly titrate people up on both normal fats and medium-chain triglycerides, that they can tolerate very high amounts over time. You’re right, there definitely is an adaptation that occurs over time.

What is the benefit of this to someone with Alzheimer’s? If you give them this product or if they adapt to a high-fat diet over time, what happens to their cognition, to their food cravings?

SAM HENDERSON We’ve done two clinical studies with our product in people with mild to moderate Alzheimer’s disease. The outcomes we measure are change in cognition. We use a test called the ADAS-Cog test [Alzheimer’s Disease Assessment Scale-Cognitive], which is a test of a variety of measures of cognition, in particular short-term memory, which people know is one of the first things that’s affected in Alzheimer’s disease. In our first study that we published in 2004, you can see a very rapid change in improvement in cognition when people take the MCTs.

How long did that improvement in cognition last?

SAM HENDERSON The way the study was done was, they were given one dose of the MCTs and their cognition was tested 90 minutes later, and we could see an improvement in cognition in 90 minutes. But we didn’t measure any time points after that.

Do you have some clients, are there some patients who have been on your product long enough for there to be any measurements of what happens to their cognition over time?

SAM HENDERSON We did another study that we published in 2009 where we looked at people who were on the products for 90 days. We saw improvement both at day 45 and at day 90 in a particularly genetic subpopulation of the subjects. So we can see the long-term benefit, at least for 90 days.

If it was my grandmother or my aunt, I’d like to see it work for nine years.

SAM HENDERSON We would have to do that study, which would be a very difficult long-term study. Our next study we setting up is for six months, so we’ll get another, longer data point. To do these very long-term longitudinal studies is very challenging, especially for a small company like us.

Are you getting any help from the National Institutes of Health or any groups that are concerned about Alzheimer’s?

SAM HENDERSON We have not got any grants from National Institutes of Health.

What other conditions do you think this might potentially help, to have somebody be on a higher-fat diet, or just on more of these medium-chain triglycerides?

SAM HENDERSON If you look in the literature, there was an experiment done a couple years ago in Parkinson’s disease where they tried a ketogenic diets and they noted some improvements in measures of movement in Parkinson’s disease. There’s some suggestion in the literature for some other conditions, like epilepsy, obviously, which has been known for a long time that pediatric epilepsy, especially for non-responders to the current therapies, when they’re put on these ketogenic diets they see very strong reduction in seizure frequencies. Those are the two ones that I think have a good probability of success.

I’m thinking now that a lot of these that we’re talking about are nerve diseases, diseases that involve nerve systems or brain as nerve, so systems that are damaged that have nerves in them. Could we put possibly multiple sclerosis in there, muscular dystrophy, possibly Lou Gehrig’s disease? Anything that has a nerve damage component to it, people with brain injuries?

SAM HENDERSON We haven’t studied any of those conditions, so we can’t make any sort of off-label claims to any of those conditions.

But what about as a scientist, as you look at just how nerves function and how metabolism functions? What’s your guess?

SAM HENDERSON There’s good reason to suspect that ketone bodies may be advantageous in numerous neurological conditions, mostly because the neurons will constituently metabolize glucose. This is why you see a lot of neural problems in people with diabetes, because their blood glucose gets too high and they generate lots of what are called reactive oxygen species when they metabolize glucose. So ketone bodies may be beneficial in a lot of those neurological conditions, but we haven’t studied that, so we can’t make any claims to that.

You can’t make any official claims, which makes me think you have gotten approval to make claims about some diseases. What has the FDA approved your product for?

SAM HENDERSON Our product is a medical food. There’s no official approval from the FDA. For a medical food, you just basically have to do studies, you have to demonstrate that it actually works in clinical studies. You need two adequate and well-controlled studies. And then it has to be backed up by scientific evidence. Then you can actually make a disease claim. Like, our label claim is for the metabolic processes associated with mild to moderate Alzheimer’s disease. So we can make a disease claim, and right now it’s mild to moderate Alzheimer’s disease because that’s what we’ve studied in our two studies.

So you can make that claim because you have two peer-reviewed studies that have been published in scientific journals? That’s the certificate?

SAM HENDERSON For medical food, that’s what’s required.

If I wanted to get this product, where could I go to get it?

SAM HENDERSON Medical foods have to be administrated under medical supervision. That means for our product you need a prescription. You have to go to your doctor and have them write you a prescription. Then you go to your pharmacy and you can get it at any pharmacy in the U.S., Wal-Mart, Costco, Rite-Aid, Walgreen’s.

Is it expensive?

SAM HENDERSON It retails for about $80 to $90 a month.

Is that for the size of a bottle of olive oil?

SAM HENDERSON No. It comes as a powder that you mix up. You get a 30-day box, which is a fairly large box, which contains 30 little pouches or packets. You mix that with water or juice or whatever you want.

I’m picturing that it’s oil that’s been suffused with some kind of coating that dissolves in water, and then lets the oil be out and there you have it?

SAM HENDERSON We use a matrix to encapsulate the oil. It’s quite similar to the matrix that’s used in ice cream, sort of a protein-maltrodextrin matrix, which is very stable and creates a very stable emulsion which helps digestion and relieves some of those adverse events. You can mix that product in whatever you want. We have people who mix it with puddings and soft foods, which people seem to like. I kind of like it in orange juice, because it has a sort of Orange Julius-type flavor to it.

So there are ways you can take it in. What if the logic of eating a higher-fat diet and a lower-carbohydrate diet appeals to someone? You wouldn’t want to mix it in orange juice then.

SAM HENDERSON If you’re trying to cut out your carbohydrates, you’d just mix it in water. It’s vanilla flavored, so you can just mix it in water alone.

And it doesn’t have enough carbs in it to pop somebody out of ketosis?

SAM HENDERSON No. I think it only has two grams of sugar in it.

What size of serving?

SAM HENDERSON That’s a 40-gram serving.

So one time a day you would add 2 grams of sugar to your total load of sugars?

SAM HENDERSON Right, which is pretty low.

If a person could inform their doctor about this product and their interest in it, they could use it for anything they’re curious about?

SAM HENDERSON If you could get your doctor to write the script for it, yeah.

Doctors write scripts for a lot of off-label uses. I’m wondering, if somebody was curious about this, where it would be potentially the most helpful, there are a number of studies that say if somebody’s switching to fat-burning or they’re going to do a fast, the first 24 hours is the toughest part. After someone gets through 48 hours, there’s some metabolic shifts that tend to happen where it’s a smoother process. But for some people, that first 24 hours is really uncomfortable and might even be stressful on their body.

SAM HENDERSON I’ve done those at-home experiments where you try and drive yourself into ketosis as quick as possible. Usually if you read around the Internet, body builders tend to do this a lot. If you exercise very vigorously on that day you quit the carbohydrates, you can deplete your glycogen stores, and that’ll push you into ketosis much more quickly. Or you can drink some Axona, which will push you into ketosis in 20 minutes.

Does that feel different? Once you’re in ketosis, can you feel it? Is it just a subtle thing?

SAM HENDERSON We haven’t had any reports of people feeling any differently other than improved cognition in Alzheimer’s patients.

How about somebody who has trouble shifting into an Atkins-style diet? Could it be like the Nicorette of switching to fat-burning, to take in this medium-chain triglyceride?

SAM HENDERSON [laughs] I guess you could think of it that way, if they’re trying to acclimate themselves to being in ketosis.

And we’re talking theoretically. Nobody has tried this?

SAM HENDERSON Not that I know of.

In a true fat-burning mode, there’s other things that happen besides having ketone bodies. For instance, insulin levels go down, leptin levels go down, the cells become more sensitive to the signaling of a lot of hormones. If somebody’s taking in carbs, that’s not going to happen. Are there some benefits that could be lost if somebody just takes in this kind of product and keeps eating ice cream and cookies and sodas?

SAM HENDERSON If you keep eating carbohydrates in your diet, you’re not going to lose weight, obviously, because you’re stimulating your insulin signaling, which is a fat storage protein hormone, you’re going to stimulate the storage of fat. So the studies that have looked at MCTs for weight loss mostly focus on the satiety thing, that once you take the MCTs you don’t really feel hungry any more. That’s probably due to that queasy feeling that you get in your stomach and you just don’t want to eat. Also, people who have been on an Atkins diet know that people self-limit their caloric intake when they’re on that kind of diet. I’ve done this many times, but after a while on eggs and ham and tuna and steak is just like, “Bleah, I don’t want to eat that any more.” People just naturally limit their calories without having to consciously do it.

There’s another theory of that. You get bored with that kind of diet, is what you’re saying.

SAM HENDERSON Yeah.

One could argue that maybe you need a better chef who can make a low carb diet more varied for you.

SAM HENDERSON That’s probably true. I’m a terrible chef, so I always have a hard time sticking on it.

The other side of it is that it may not just be the boredom of food that changes somebody’s attitude towards the food, it may be that appetite signals, as hormones become more sensitive, go down, so that a person isn’t just bored with their food, but their body is telling them accurately, “You had enough food. You don’t need more food.” And we know that because our energy metabolism signaling is more clear now. It’s not as gummed up and muddied by having insulin and leptin and all kinds of other hormone signals be way too high. The body’s operating more intelligently.

SAM HENDERSON I think that’s absolutely right. Because fat is one of the main satiety signals to your body. If you take in a lot of fat, if that’s all you’re eating, you’re absolutely right, your body is saying, “I’ve had enough. I don’t want to eat any more.”

And it’s partly a satiety signal for your stomach, getting that kind of nutrient, but metabolically, once it’s in the bloodstream, your body doesn’t really want to be fat. It wants to have enough fat, but it doesn’t need to be super-fat. And your body knows that if the signaling is accurate for it.

SAM HENDERSON I personally think your body wants to be fat. What your body wants to do is store fat for when you run out of food later.

I’ve always wondered about that argument. There’s a lot of debate about that. Why is it that people when they’re older, past their reproductive years, is when they’re most likely to be fat, and when they’re young is not when they’re likely to be fat? Our temperatures don’t go up every year just because we’re getting older.

SAM HENDERSON I think when you’re younger, you’re competing for mates. You tend not to want to be fat. But you look at the obesity epidemic now, high school kids, they’re pretty fat. I think the big issue is, it’s this “thrifty genotype” hypothesis that Neel came up with in the ’60s, that you want to store fat for when you’re going to run out of food. For most of human evolution, people probably ran out of food fairly regularly, so they want to store fat as readily as they can. So when you take in all these carbohydrates, what your body does is, it says, “Let’s just store fat. Let’s get fat, because we’re going to run out of food next week and we’re going to need all this fat.” To me, that’s the fundamental shift that occurred in human diets. As soon as we found this very abundant source of carbohydrates in terms of grains, people could get as fat as they wanted easily, whereas in the past it was probably difficult for them to find carbohydrate-rich food all the time.

Maybe there’s some truth to that, or maybe the thrifty gene hypothesis is fundamentally wrong. Who knows? But to get back to your product and the idea of what people need when they’re sick, and especially with a neurological disease, there may be reasons to have them try out a way to pull back on carbohydrates, find ways to nourish their system with foods that make it easier to shift into making ketone bodies. This may be kinder to their appetites. They might not be tortured by carbohydrates the way they are when their body is really starving, because that whole system has gotten so messed up, every sugar that they eat doesn’t get to their cells as energy.

SAM HENDERSON The idea of shifting to a low-carbohydrate diet has lots of benefits, not only weight loss and neurological conditions, but probably other things as well.

Theoretically, what do you think about this kind of product, the medium-chain triglycerides, for serious illnesses, someone who is at a very dire strait in terms of a neurological disease? Would there be any harm for them trying this kind of product as a way to see if their damaged nerve cells might get a little more nourishment and might be destructed more slowly?

SAM HENDERSON That’s one of the benefits of using this. It’s already a GRAS-approved food additive. GRAS generally recognized as safe by the FDA, which is a much higher standard of safety than any drug. Most drugs I wouldn’t want to take because of the side effects. Food additives and these GRAS substances have to be reviewed by the FDA as to whether or not they’re safe for human consumption. Since it is a food ingredient, it’s pretty safe, other than some GI upset you can get with taking large doses of it.

You think that this product might help people with cognitive impairment, some studies you’ve done have shown that, if they have Alzheimer’s. You think it has some potential for some other nerve diseases that haven’t been officially studied. And you think it might not hurt somebody to try it if they’re curious about this, even with a serious condition, or if they just have cravings and they want to see what happens to their cravings if they get more ketone bodies into their bodies earlier.

SAM HENDERSON If you look at the literature on ketosis, especially in the last couple of years, you can see a lot of potential applications.

Sam Henderson, it’s not just people that you’ve studied that product in, you’ve also looked at it in some animals, such as dogs. What happened when you used it in dogs? How did you use it?

SAM HENDERSON We did a few studies in dogs to look at a couple things. One is cognition in the dogs, in older dogs. Dogs suffer from an Alzheimer’s-like syndrome called canine cognitive decline. If anyone has an old dog, they probably know the symptoms of that, a bit of wandering, less human interaction, less like a puppy, less like a young dog. We supplemented their diets with the MCTs and we noted improvements in several measure of both canine cognition and motor control. They were able to do motor tasks better and their cognition was better. That study was replicated by a scientist at Purina, so it’s been independently validated.

What does “motor cognition” mean?

SAM HENDERSON It was a motor task. What they did was, they had to reach their paw out and grab a little treat and pull it towards them. They dogs who were given MCTs could do that task better than the dogs who were given the placebo. Their motor skills improved. These are older animals. We also looked at how the mitochondria were functioning in their brain.

That’s the little engine that’s the furnace inside the cells that helps our whole body get energy?

SAM HENDERSON We knew that ketone bodies act mainly in the mitochondria, so we looked to see if this induction of ketosis could improve the function of these mitochondria in the brains of the dogs. You could see a big improvement in their respiration rate. They were able to more efficiently utilize the fuels that they were given.

Meaning that they didn’t have to work as hard to breathe?

SAM HENDERSON They could generate more energy using less oxygen, so they were much more efficient. The other thing we looked at was the composition of lipids, fats, in their brain. The reason we did that was that Dr. Taha, who wanted to do this study, had worked on these ketogenic diets, and he knew from these previous studies that when you put kids on these ketogenic diets— (You mean children with epilepsy, for instance?) Right.

By the way, that ketogenic diet for epilepsy has been tested at Johns Hopkins especially, and it is one of the most effective, often more effective than most drugs in terms of eliminating or reducing epileptic seizures.

SAM HENDERSON Absolutely. There’s probably 50 years of research on that. It’s a very effective treat. So in this study that Dr. Tata had looked at, previously he found that when you put these kids on these ketogenic diets, their blood levels of these omega-3 fatty acids goes way up, even if you don’t supplement the diet with things like DHA and EPA. The blood levels go way up, the idea being that when you stimulate fatty acid oxidation, your body releases these polyunsaturated fatty acids, PUFAs, which are really good for you, as everyone has heard about the benefits of fish oil and things like that. What he wanted to see is, if you tricked the animal into thinking it’s in ketosis, does this same thing happen?

When you say “trick” the animal, this is not like hiding a treat and saying, “My beloved dog, I’m going to try to trick you,” this is fooling their body cells into doing something, not just the dog’s behavior, right inside of their trillions of cells?

SAM HENDERSON Right. Instead of putting them on a ketogenic diet, we just gave them the MCTs so the liver would make ketones out of that, instead of the liver being in a carbohydrate- and protein-restricted environment where it would make ketones. That’s sort of the trick. When we did that, then we measured various lipid levels in their brain. You see a big change in the lipid environment in the brain of these old dogs. People think fat is bad, but your brain is mostly fat. There’s a very large amount of fat, and as you age, the cholesterol levels and fat levels in your brain go down. This is bad. This is also the sort of thing that happens in MS. You get this depletion of fatty acids in your brain.

And in a lot of other neurological diseases, Parkinson’s …

SAM HENDERSON  Exactly. What was interesting was that we found that the total lipid content of the brain went up and you could see specifically increases in those omega-3 fatty acids in the brain, like DHA and EPA, which are used in the composition of the lipid membranes in the cells of your brain.

You don’t know whether that’s because those nutrients were supplied in greater amounts or that the body, once it wasn’t burning inefficiently, was able to save those fatty acids and use them more effectively as building materials. It could be that it already had these materials there but it used them in a better way once it was a cleaner metabolism?

SAM HENDERSON Right. His hypothesis was that once the body is in this fat-burning mode, once you switch it over, either by dietary means or giving it an MCT, your body will start to release all these polyunsaturated fatty acids, these omega-3s and omega-6s, which then enter the brain and can be used to rebuild the lipid membranes in your brain. It was an interesting study we did. We published that in 2009.

Sam Henderson, this makes me very curious about all the different ways that product might be used. I know you only have one FDA-approved official medical use for this product, which is the Alzheimer’s disease, but I can’t help but think of all kinds of ways that I might like to use this and try it out and experiment with it if I had all kinds of different diseases. You don’t mind if I just express that wish, do you?

SAM HENDERSON No, but keep in mind that medical foods are not approved by the FDA. They look at it, and if they think it meets the thing—but they don’t ever issue an approval letter for a medical food.

But I can claim an interest in the possibility that this kind of food might help people with a lot of different conditions. It’s intriguing that it might. I can say that. Can you say that?

SAM HENDERSON No, I really can’t say that.

Why not? You’re a scientist. You can talk about the theory of these things. Why can’t you say that, with all that you know? It’s obvious to me that this has the potential. Why can’t you say that, too?

SAM HENDERSON Since we’re selling a product, we’ve done—to our credit, we’ve actually done studies to demonstrate that this product works in Alzheimer’s disease, for us to speculate that it would work in MS or PD without actually doing the studies would be a little bit irresponsible on our part. We really need to do those studies and then make those claims.

So I can say as a person asking you questions, “Boy, it seems like common sense that this might be a potential mechanism that might help somebody with Parkinson’s disease or with MS or with another neurological condition. It might be something that might be worth looking into.” I could say that. I could be curious about that, but because you’re selling a product, you really can’t say that?

SAM HENDERSON That’s correct.

2 comments for “Sam Henderson – Ketones, Alzheimer’s and Nerve Protection

  1. January 16, 2014 at 2:57 pm

    Hi, James,

    We don’t give medical advice on this website. I’d suggest contacting Sam’s company directly for your answer.

  2. James H. Getzen, M. D.
    January 8, 2014 at 2:15 pm

    Please send me information concerning edema of the legs when using Anoxa. I understand I am to decrease carbs and increase protein. Is this correct? I recently needed to stop taking Anoxa for 2 days to relieve leg edema. Please address this point.

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