نوزادان در مورد آلزایمر چه می توانند به ما بگویند؟

What can Babies tell us about Alzheimer’s?

In 1906, Dr. Alois Alzheimer requested to examine the brain of a patient named Auguste Deter who appeared to have no sense of time or place and could barely remember basic details of her life. In her brain he found abnormalities that remain to be the hallmarks of Alzheimer’s disease today, making Auguste the first known patient with the disease. “Now here’s the even more striking thing.

If Auguste had instead been alive today, we could offer her no more help than Alois was able to 114 years ago.” In a 2015 TED talk, Samuel Cohen points out that despite having discovered the disease more than 100 years ago, no real progress has been made in the fight against it.

Cohen explains that Alzheimer’s is certainly not a part of normal aging and it is a disease that can be cured. “…we’ve managed to identify a critical step in the process and are now testing a new class of drugs which should specifically block this step and stop the disease.”

However, while Cohen and his team’s work will surely be productive, it’s very unlikely that a single drug will cure the disease. That is not to say that the disease cannot be treated, but… why is this?

And what does Alzheimer’s have to do with babies? And finally: What do babies, coconut oil and breast milk all have in common? To understand, let’s start with a story from Dr. Mary Newport. In May 2008, her husband Steven received a MRI and was diagnosed with Alzheimer’s disease.

That same year, Mary took Steve to the University of South Florida - hoping that he’d be able to qualify for a new vaccine study that might help his condition. Unfortunately… he was unable to achieve the necessary score of 16 on a mental state examination to qualify for the study - he only scored a 12.

Around this time, Mary had heard of an upcoming drug called Ketasyn, or AC-1202 which had brought about significant improvement over a 90-day period in half of subjects with a specific genetic profile. In a pilot study, some Alzheimer’s patients improved on memory testing with the very first dose.

Mary then learned that the promising ingredient in Ketasyn is MCT oil and that the dosing was just 20 grams. Mary found out that the MCT oil was derived from coconut oil and calculated that 35 grams of coconut oil should contain 20 grams of MCT oil and so she put this amount - a little more than two tablespoons, in Steve’s morning oatmeal.

Four and a half hours after having his breakfast, Steve went again to University of South Florida to be retested for the same trial mentioned earlier. This time he scored an 18 on the mental state examination …two points higher than the necessary 16.

60 days after Steve began taking coconut oil for its MCT content, Dr. Newport wrote this case study, commenting that “He is able to concentrate on things that he wants to do… and stay on task, whereas before coconut oil he was easily distractible and rarely accomplished anything…”

Here are three clocks he drew as part of a mental examination, one the day before he started taking coconut oil, one just two weeks after and one 37 days after. Now, this is just one anecdote and the MCT in coconut oil did not “cure” Steve’s Alzheimer’s, but he did improve significantly.

MCT, or “medium chain triglycerides” are not usually a significant part of the average adult’s diet, a baby however would be getting a reasonable amount of them from breast milk. In fact, MCT’s are added to commercial infant formulas to mimic the composition of breast milk.

And MCTs are even stored in babies’ fat tissue. What is interesting about MCT oil is that it acts as a different source of fuel for the brain, rather than glucose. (Just to be clear, blood glucose is the same as blood sugar, which rises when you eat carbohydrate) Late last month I had the chance to interview Amy Berger, author of the Alzheimer’s Antidote where she explained the significance of not having to rely on sugar, that is - glucose, for fuel.

“So, um, yea, I would say Azheimer’s is a fuel shortage or an energy crisis in the brain. And where that comes from is that the major problem in the brain of somebody with Alzheimer’s is that neurons in affected parts of the brain lose the energy to effectively metabolize glucose. So they’re basically starving.

They’re starving for energy, they’re withering, they’re shrinking, you can see the volume of the brain shrinking on an MRI, you can see that it’s smaller. And all that comes because the brain is starved for fuel and the brain is what we call an Energy Intensive Organ, it only accounts for about 2% of an Adult’s Body weight but it uses between 20 and 25% of all the glucose and Oxygen.

So the brain, you cannot have an interrupted fuel supply to the brain or you’re going to be in major trouble.” In her book, Amy explains that “compared to healthy people, Alzheimer’s Disease patients have shown up to 45 percent reductions in cerebral metabolic rate of glucose” - essentially up to a 45% reduction in the rate the brain uses glucose for energy.

And, It’s almost always observed that the Alzheimer’s brain is under metabolizing glucose. So what is going on here? Are we seeing that the brain cells have died or is it that they are alive and just unable to utilize glucose?

If the cells were dead, then - as Dr. Stephen Cunnane points out here, those cells shouldn’t be able to use any sort of fuel. As he shows on this slide, you can see that as indicated by less red shading, glucose uptake progressively reduces as you progress from mild cognitive impairment to Alzheimer’s disease.

However, the Alzheimer’s brain has no problem using ketones for energy. Not only that, as he shows here, the Alzheimer’s brain actually uptakes ketones better than controls. Very simply put ketones are a source of energy naturally produced in the body from fat when dietary carbohydrate is restricted enough.

So, if the key problem with Alzheimer’s is that the brain is lacking adequate fuel due to an inability to utilize glucose, then it makes sense that providing an alternate fuel would cause improvements. The significance of the earlier mentioned medium chain triglyceride, MCT oil - is that MCTs are quickly transported from the gut to be rapidly oxidized in the liver and turned into ketones.

For example, In comparison to the long chain oleic acid, the medium chain caprylic acid is oxidized 5 times faster in liver cells. To highlight this point, here’s Dr. Stephen Cunnane showing that after 6 months of 30g of MCT oil supplementation, people with mild cognitive impairment show a doubling of the uptake of ketones in the brain. However, this doesn’t matter if getting more MCT oil into the stomach and getting more ketones into the brain doesn’t improve cognitive function.

But… it does. Dr. Cunnane shows here that 6 months of MCT supplementation improves scores on a battery of cognitive tests in people with mild cognitive impairment. Before we continue, I’m guessing that if you are into reading about health and dieting, ketones are probably starting to feel like cranberries in the year 2000 … “I don’t know what’s going on with cranberries, but they’re getting in all the other juices!”

“Showing up everywhere - hey what do you got apples? Put some cranberries in it, we’ll call it cran-apple go 50-50. What do you got, grapes? How ‘bout cran-grape? What do you got mangoes? Cran-mango!”

It seems that with anything from weight loss to diabetes to arthritis, to brain fog you’ll find someone saying that the ketogenic “keto” diet is the answer. However, while ketones and ketosis may seem like the new fad being sold as a panacea, ketosis is not a new thing at all because virtually every human has been in ketosis at the start of their life.

As Dr. George Cahill showed in this 2006 paper, newborns are essentially starting out in ketosis at a level of about 0.5 millimoles, which is considered nutritional ketosis. By comparison, an adult, depending on their diet, would have to fast for at least 13 hours to produce that same level of ketones, and a newborn can reach more than that initial level simply by not eating for a little more than 3 hours - something that would take more than an entire day of fasting for an adult to achieve.

As this 1986 paper reveals “ketone bodies could account for as much as 25% of the neonate’s basal energy requirements in the first several days of life.” And it has been shown that ketones can provide up to 60% of the energy requirements for an adult brain. Babies may be living on ketones even before birth.

In his book on the health potential of ketones, Dr. Muneta Tetsuo, director of Muneta Maternity Clinic in Japan explains that pregnant women, whether they are restricting carbohydrate or not are producing higher than normal levels of ketones. By comparing the mother’s blood with the newborn’s umbilical cord blood, he found that out of 416 cases, 70% of babies were born with even higher levels of ketones than that of the mother.

By analyzing the villi that provide contact with the mother’s blood to the fetal membrane, Muneta deduced that the fetus must be living in an environment of elevated ketones from the start of pregnancy. And, even a month after birth, babies on average had a blood ketone level 5 times higher than that of a normal person.

And, while the older you get, the harder it is to get into ketosis, humans are generally much better at getting into ketosis than other animals. Amber O’Hearn explains this in her talk at Low Carb Houston 2018, “You might think that a dog would be in ketosis right?

A dog eats a low carb diet but in fact, if you want to get a dog into ketosis, you have to either deprive them of calories or put them through some intense exercise, or you can give them MCT oils and that would work too. But even if you completely fast a dog, it takes longer for a dog to get into ketosis and they never get into the deepest levels that a human would get into.”

So what’s interesting about human babies’ brains is that while they have an even higher demand for energy, as much as 3 times as what the adult brain requires, they are relying on ketones, a fuel that modern people rarely utilize, because fasting or heavy carb restriction are necessary to get an adult into ketosis.

And, while Alzheimer’s patients are having trouble using glucose for energy, their brains, like a baby’s brain, can run just fine on ketones. But of course, most people have no trouble running their brains on glucose - In fact it was thought for a while that the brain could only run on glucose.

So what is going on that messes up the brain’s ability to take up glucose? I can’t share the whole picture in this one video, but for starters, consider this: it’s estimated that 80% of Alzheimer’s patients have insulin resistance or Type 2 diabetes. (Just to clarify insulin resistance is what leads to diabetes) And, women as young as 24 years old with a form of insulin resistance due to polycystic ovary syndrome have reduced metabolism of glucose in the brain that looks strikingly similar to what you’d see in a 65 year old brain.

In fact, Alzheimer’s is frequently referred to as Type 3 diabetes. Though… it’s not as simple as you first get Type 2 diabetes and then you progress to Type 3 diabetes from there. “So… I guess the logical step would be… OK you get type 2 diabetes and then you progress into Type 3 diabetes… is that accurate?” “Partly but not fully.

So, having type 2 diabetes is a risk factor for Alzheimer’s or cognitive decline, so you are at increased risk to have dementia later in life, if you’re a type 2 diabetic, but, not everybody with type 2 diabetes will develop Alzheimer’s and not everyone who has Alzheimer’s had or has type 2 diabetes.

So the thing is: When we talk about type 2 diabetes, we only ever talk about blood sugar - blood glucose. They never look at insulin, so there’s a lot of people walking around right now with totally normal blood sugar, but the blood sugar is only normal because it’s being kept in check by sky high insulin.

And in a lot of modern illnesses, what we call non-communicable diseases - meaning not something you can catch like a cold or flu, not something contagious, some kind of chronic illness that’s not … - like type 2 diabetes, like obesity, PCOS, cardiovascular disease, non-contagious illnesses… So many of these are driven by chronically high insulin, even when blood sugar is normal.

So you can get any of those things, whether its hypertension, pcos, gout, all these things that are driven by insulin, even people’s sugar is normal.” “The same thing is true for Alzheimer’s. Chronically high insulin is a major risk factor for Alzheimer’s, regardless of what genes you have.” To simplify a very complex issue, chronically high insulin is what drives insulin resistance.

When you eat carbs, insulin is secreted to transport glucose into the cell. When insulin is constantly being secreted in response to excessive low fiber carb intake, your cells become resistant to the effects of insulin, similar to how frequently drinking alcohol makes you resistant to the effects of alcohol.

As Dr. Georgia Ede explains here, insulin has many important functions in the brain other than just glucose regulation. And, there are insulin receptors on the blood brain barrier to get insulin into the brain so it can perform those functions.

But when the blood brain barrier is constantly flooded with insulin, it becomes resistant to it by downregulating insulin receptors. So, you can reach a state where you have plenty of glucose in the brain, but not enough insulin to use it. The hippocampus, the region of the brain largely responsible for memory formation, has a particularly high glucose demand. And while many brain cells have Glut-3 receptors which don’t require insulin, the hippocampus also has Glut-4 receptors which do require insulin.

And, one of the earliest detectable traits of Alzheimer’s disease is a compromised hippocampus. And Of course memory problems are a well understood sign of cognitive impairment or Alzheimer’s disease.

Now, there is one more point about insulin I want to share and it has to do with beta amyloid, which I’m sure you’ve heard of if you spent any time looking into Alzheimer’s disease as beta amyloid plaques are one of the hallmarks of the disease.

“I think, some people who might be a little bit more into this topic, they might’ve heard of Amyloid Plaque and they might be saying ‘Oh, maybe it’s the Amyloid Plaque that is like choking neurons and so they can’t get the glucose. Is that accurate or is it not, and can you comment on that?’.”

“It’s, it is accurate but the implications are not what we’re normally told about this amyloid stuff. So um, I don’t know how much time we have to get into detail, but amyloid or beta amyloid is this protein that the neurons secrete that even healthy people’s brains secrete, it’s not specific to Alzheimer’s. The problem in Alzheimer’s is that these proteins are not cleared away properly, so when they’re secreted they just build up and build up…. and form these infamous plaques.” “We were talking about… Amyloid plaque seems to be kind of choking the neurons ability to utilize glucose.

Is there a mechanism around that that you can talk about?” “Yea so I do think there is a physical aspect to it that these plaques do build up outside the cell and they actually block synapses, they block neuronal signal transmission, but, biochemically - so I’m gonna get a little nerdy, hopefully the audience is not gonna be bored here, but… this amyloid inhibits an enzyme called pyruvate dehydrogenase, and this enzyme, pyruvate dehydrogenase is the connection between glycolysis and the krebs cycle - so it’s two ways to produce energy from glucose.

We convert glucose to pyruvate through the process of glycolysis, and then we convert pyruvate to acetyl-CoA, which then gets burned, gets oxidized for energy, to produce energy through the krebs cycle. And pyruvate dehydrogenase is the connection between those two.

And beta amyloid puts the breaks on this enzyme.” “What is it that degrades the amyloid plaque, what clears it out - you were saying that’s one of the issues, it’s not getting cleared out.” “Yea this is really one of the most shocking things I came across in my research on this is that - remember I said these plaques, these amyloid proteins are not really a problem - even healthy brains secrete them.

The problem is that in Alzheimer’s, they build up, they’re not cleared away properly. There’s an enzyme that clears this stuff away and it’s called insulin degrading enzyme, I mean how weird is that?

So this enzyme, IDE, insulin degrading enzyme has more than one target that it works on, these - beta amyloid is one of its targets, insulin is another of its targets. And the thing is, enzymes have different affinities - different sort of like favoritism for one target, one substrate over another.

And the favorite of this enzyme is insulin, the affinity of this enzyme for insulin is so high that as long as there’s a lot of insulin swimming around in the blood stream… this enzyme is so busy going after all these insulin that it’s going to ignore and neglect all of its other targets, including this beta amyloid.

And they know that in people that have hyperinsulinemia who have chronically high insulin levels, they have more beta amyloid buildup.” “You can have Alzheimer’s disease without a lot of plaque buildup in the brain and you can have a lot of plaque buildup in the brain and not have Alzheimer’s. So um, we can’t pin everything on this amyloid if not everyone who has Alzheimer’s even has a lot of this plaque.”

This complexity of the disease that Amy Berger has highlighted brings us back to my first point that it’s very unlikely that a single drug will cure the disease. As Dr. Dale Bredesen, author of the “End of Alzheimer’s” points out, the drug would have to do the following 36 things: That is not to say we need 36 different drugs - Dr. Bredesen likens this situation to a roof with 36 holes.

You can plug some of the holes with drugs, but you’ll have to plug many more of them with lifestyle interventions like adopting a ketogenic or low-carb diet, consuming MCT oil, making sure you are getting sufficient amounts of certain vitamins and minerals, getting sufficient sun exposure, optimizing sleep, exercising, and more as part of his ReCODE program.

Here is Dr. Bredesen explaining the case of a physician - who was… basically a genius, having gone to a major university when he was only 15 years old, but as of 2014 was suffering cognitive impairment.

As a classically trained physician he was very skeptical of Dr. Bredesen’s approach… “so, everything I would say he’d say ‘That’s not important, that’s not important.’ So finally after a few minutes I said look, give me six months, if I can’t make you better then go elsewhere.

He said there is no place else.” On the program he drastically reduced his fasting insulin and made significant improvements in other important markers. More importantly his cognition improved significantly - in just 3 months his wife called Dr. Bredesen to tell him how much sharper he had become.

Dr. Bredesen wrote that in just 10 months, he went from struggling to perform mentally to seeing patients full time. Interestingly, the volume of his hippocampus increased - going from the 17th percentile to the 75th percentile.

The neuroradiologist who did the second MRI insisted the apparent increase in brain volume was a mistake because they had never seen that in the 75,000 scans they had done in the hospital. Dr. Bredesen took the films to be analyzed elsewhere and confirmed that this person had indeed increased the volume of their hippocampus on the program.

This is just one person, but not the only person who made improvements on the program. Dr. Bredesen published a research paper in 2016 documenting 9 more case studies of patients who improved biomarkers and their cognition on his program, and there are still many more undocumented cases.

Dr. Bredesen says that there are at least 3 types of Alzheimer’s, so if you are trying to treat or prevent it, your approach will be different depending on which type you have. Alzheimer’s is, as you’d expect - complicated.

But that does not mean there is not plenty of useful information out there. Just because there’s not a single pill or even a handful of pills we can hold up and say is the cure to Alzheimer’s, that doesn’t mean there’s no way to prevent, stall or even reverse the disease.