26 minute read
Drop acid
Dr David Perlmutter
Drop Acid doctor warns of evolutionary mismatch
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Robbins: David, your new book is titled 'Drop Acid' but it has nothing to do with taking LSD.1 It's about the importance, the really critical importance, it turns out, of reducing our uric acid levels. Now, most people have never heard of uric acid. In
Western medicine, it's widely recognized that when there is too much uric acid in our bodies, crystals of uric acid can form, and then these crystals can settle in our joints and cause gout or settle in our kidneys and form kidney stones.
But other than those two conditions, gout and kidney stones, the medical profession as a whole tends to think of uric acid as a harmless waste product that's normally excreted in the urine.
What I hear you saying in your book, though, is that this view is wrong. Because high uric acid levels, in fact, contribute substantially to a host of problems as diverse as obesity and diabetes, nonalcoholic fatty liver disease, high blood pressure, heart disease, stroke,
Alzheimer's disease. The list is very long. In fact, you call uric acid 'the hidden connection' linking our modern ailments. This is a huge topic, what do you hope that your book accomplishes?
Dr Perlmutter: Let me first take a step back and look at the notion that the number one cause of death on planet earth right now is not some virus we might catch. The number one category of issues that threaten us is what we call chronic degenerative conditions.
Things like, coronary artery disease, Alzheimer's, various forms of cancer, type 2 diabetes. These are the most threatening to us.
What is important about these issues, and others, is that they are at their core the manifestation of metabolic mayhem, metabolic disturbances. When we talk about metabolism, we often talk about something called metabolic syndrome.
I'd like to open up that term a little because it is strictly defined as being characterized by five things: elevated blood sugar, elevated body fat (BMI), dyslipidemia, problems with high blood pressure, and elevated triglycerides.
So each of those is a problem in and of itself. In the aggregate, they form something called metabolic syndrome. To indicate how pervasive these issues are here in America: 88% of adults have at least one of these components, meaning that only one in eight American adults is metabolically intact.2 Being metabolically compromised, as in seven of eight American adults, sets the stage for those chronic degenerative conditions — the number one cause of death on our planet. This article is a partly abridged account of an indepth interview conducted by Ocean Robins and podcast on The Food Revolution Summit, 2022. Dr David Perlmutter discusses the dangers we face from high uric acid levels and explains why, unlike humming birds, we're no longer genetically equiped to cope with them. Dr Perlmutter is a board certified neurologist and six-time New York Times best selling author whose books have been translated into 32 languages.
In 2016, a study came out which was titled, “Uric Acid in Metabolic Syndrome: From an Innocent Bystander to a Central Player.”3
What it describes is the fact that for many years, we've seen that patients with diabetes, with obesity, with hypertension, have, in addition, interestingly, high uric acid. Until fairly recently, we've looked upon that and said, “Well, isn't that interesting? Maybe they have an increased risk for gout. No big deal.”
But we've come to understand that uric acid which we are seeing elevated in these and other problems, is actually playing a role in their genesis. It's playing a mechanistic role. One very large study came out in 2009 and looked at 90,000 people — 42,000 men, 49,000 women — and it followed them for eight years.4
What they found was that in people who had a uric acid level that was elevated, meaning in their case above seven milligrams per deciliter, in these people who originally at the beginning of the eight-year study had an elevated uric acid — their risk of death after the study was completed, of having died during those eight years for any reason whatsoever (we call that all-cause mortality) was increased by 16 percent.
The risk of death from cardiovascular disease was increased by close to 40 percent. The risk of death from stroke increased 35 percent. And even more fascinating was the finding that for every one-point elevation of the uric acid level above seven, there was an increased risk of 8–13 percent of dying from any cause whatsoever, and that was additive with every point above seven.
So does it become an issue that we should pay attention to? You bet it does.
When we understand what elevation of uric acid tells the body, we begin to understand why it would be associated with as much as a, 55 percent increased risk of Alzheimer's, an 80 percent increased risk of dementia and an incredible 166 percent increased risk of what is called vascular, or mixed, dementia.
Elevation of uric acid increases inflammation, damages the function of the energy production in our cells called the mitochondria, and leads to increased activity of what are called free radicals or more technically, oxidative stress. All of those things threaten our health momentarily, threaten our longevity overall, and certainly also in the long run threaten our health span. We've got to pay attention to uric acid. That's for sure. Brain function and dementia
Robbins: We've known for some time that there are certain conditions that are strongly correlated with increased risk for cognitive decline and brain shrinkage, and dementia. And these conditions include elevated blood glucose, insulin resistance, obesity, diabetes, hypertension, and of course, chronic inflammation.
Another risk factor for, and actually a predictor of, cognitive decline is simply the size of a person's belly or more precisely their waistto-hip ratio. It sounds, from what you're saying and what you've written, that we should now add elevated uric acid to the primary list of risk factors for impaired brain function and dementia.
Dr Perlmutter: Absolutely. These relationships of elevated uric acid with immediate cognitive dysfunction and long-term risk for dementia are certainly within our grasp to understand. And when I say immediate cognitive function, there is one study that was published — again, Japanese literature, they're pretty much way ahead of us in terms of understanding uric acid.5
Looking at 228 elderly individuals, basically what they did was they measured their uric acid, did MRI scans, and also measured their neurocognitive function.
What they found was that people with elevated uric acid right now, not eight years in the future, were four times more likely to have cognitive testing showing early dementia and their MRI’s were significantly abnormal with vascular changes - meaning evidence of small strokes, evidence of atrophy or lost tissue.
So again, it becomes a very exciting and empowering notion that we have a new metric in town that we can fix. With the help of this new metric we can not only bring about an improvement in terms of the current function, but also, more importantly, in terms of long-term risk.
We’ve learned to look upon uric acid as a danger signal for the body, an alarm signal, if you will — telling the body that winter is coming, telling the body that we might not have food or water in the very near future and signaling the body to make important changes, like increase the blood pressure, increase the blood sugar, make a lot of body fat and store a lot of body fat, lock it up.
Nowadays, we are confronting that survival mechanism with the absolute opposite — a time of, generally, food being plentiful, targeting this body that we have, this physiology that really wants to be very thrifty with our food and pack away fat for the winter, and yet, you know, this is the winter that never comes.
Robbins: So what I'm hearing is that uric acid triggers fat production, which obviously can result in weight gain and can also result in our livers becoming dangerously fat even if we aren't overweight. Since elevated uric acid levels lead directly to both increased fat production and increased fat storage, are you saying that, in our distant evolutionary past, elevated uric acid actually served an important survival purpose. Dr Perlmutter: Absolutely.
Robbins: Okay. Might this powerful survival mechanism have led to genetic mutations being passed on that cause us to experience elevations in our uric acid levels today? Dr Perlmutter: That's exactly what happened. Any subtle advantage that one group might have over another group would lead to their ability to survive and pass on their genetics, obviously to future generations.
So we inherited this elevation of uric acid which has served us, until just yesterday, very well. In other words, until perhaps the advent of agriculture — when again, our hunter-gatherer ancestors might not have done very well at hunting or gathering during one period of time or another. Having an increased ability to be thrifty and make more fat from whatever calories were around would have proven to be a great advantage to those ancestors.
And, you know, this isn't limited to primates and humans. This type of thing is going on in birds, it goes on in reptiles. You mentioned fatty liver disease, and that's a great thing. Fatty liver disease is a wonderful thing in the context of starvation or in the context of not having enough food. The humming bird connection
When the hummingbird is getting ready for its epic 1,000-mile journey, it does two things. It drinks sugar, right? It loads itself up with sugar and it makes itself have a fatty liver because that allows it to make this epic journey and increases its body fat substantially as well. When the hummingbird's ready to make this trip as much as 40% of body weight is fat. So the hummingbird becomes one
of the fattest animals on the planet.
Not only is that body fat a resource for calories for that animal, for our primate ancestors, for our hunter-gatherer ancestors, and even for humans if they face starvation, but it's also a resource for water.
When we burn fat for fuel, we create two things as end products: carbon dioxide and water for our bodies. We call it metabolic water. So this notion of storing fat away for the winter is a survival mechanism, not just because of the calories, but because it allowed our ancestors to survive during times of facing dehydration, for example.
The fructose connection forms fat. Fat is a reservoir from which we can make metabolic water — these days, not as much of a survival mechanism there, but certainly when our ancestors faced dehydration — a powerful superpower to have.
Purines and uric acid
Robbins: In your new book, you repeatedly cite the work of the
Scottish physician, Dr. Alexander Haig, who wrote a seminal book titled, Uric Acid as a Factor in the Causation of Disease.6
Now, like other famous doctors who have achieved important breakthroughs by first experimenting on themselves, Dr. Haig went on a diet designed to drop his uric acid levels, and he experienced remarkable health improvements after he did so. And in particular, what he did was eliminate meat in an effort to alleviate the migraine headaches he had suffered from for years. And it worked.
My sense is that substances known as purines had a lot to do with why eliminating meat was a key to dropping Dr Haig's uric acid levels — and thus creating so many positive health benefits, including the elimination of his migraines. What can you tell us about purines and about their connection with uric acid?
Dr Perlmutter: Purines are the breakdown products of DNA and RNA. DNA and RNA are obviously found in cells, in the nucleus of the cells, and foods that have a lot of cellularity will then have a lot of DNA and RNA. When we break them down by eating them, we will ultimately form chemicals called purines, like inosine and adenosine monophosphate, and these then are metabolised directly to form uric acid.
This is the uric acid that Dr Haig correctly identified as being associated with issues far beyond gout. As you well described, he talked about his headaches, but he also talked about other mood issues, psychiatric issues, and even cognitive issues. So the notion that these purine-rich foods, these organ meats like liver and kidneys, and certain types of seafood, shellfish, or like scallops and muscles, for example, and processed meats today can liberate purines and therefore raise uric acid — I think is very important.
Classically, the gout diet or perhaps anti-gout diet that's been talked about for decades has been one that eliminated, or at least dramatically reduced those foods that provide purines. There are only three inputs to uric acid. They are the purines of which we talk, alcohol, and fruit sugar, or fructose.
What has happened more recently is that, compared to the late 1800s during Alexander Haig's time, our fructose consumption has taken over the role of being the master, the top source of ultimately uric acid production in human physiology. Why so? Well, simply because of our fructose consumption, our sugar consumption has just exploded.
I mean, the average American is now eating somewhere around 55–60 pounds of added sugar annually. And the rise in uric acid — going from around 3.5 in the 1920s and now when the average uric acid is around 6.0 — perfectly falls in lockstep with our increase in sugar production.
Certainly, limiting purine consumption is very important as it relates to uric acid, but the big player is clearly the added sugar in our diets. When we recognize that close to 70% of the packaged foods in our grocery stores have added sweeteners, and that, by and large, these are either high fructose corn syrup or fructose or any other of its many names — it's no wonder that people are having such issues these days with elevated uric acid.7
And it's no wonder that we're seeing an incredible increase in these metabolic issues. For example, right now one in three American adults is obese. One-third of American adults are not just overweight, but obese.8 And in the distant future in the year 2030, which is far, far away in the future, right? That number's going to be 50 per cent. That's right around the corner.
The notion that 50 per cent of American adults will be obese is absolutely mind-boggling. And now that we recognize that if we can control uric acid, we have another tool in the toolbox, not just for this obesity epidemic, but for hypertension and insulin resistance and the elevated blood sugar ultimately leading to diabetes that we see. You know, when 10 per cent of children in America between the ages of 12 and 18 are diagnosed as having hypertension, my goodness, something is very wrong.9
What is wrong at the core is an evolutionary environmental mismatch. Our bodies were gifted this genomic profile that served us for 99.9 per cent of the time that we've been on this planet because, our environment was about the same. Sure, it changed over time, it would change over tens of thousands if not millions of years.
But the reality is, we've always faced food scarcity until quite recently. We've always faced dehydration, especially when we would migrate. And now we live in a very, very different environment, an environment characterized by “sedentality,” meaning we get to sit around all the time. An environment that doesn't challenge us with food scarcity, an environment in which we don't ever really fast unless it's self-imposed. And this runs counter to what our genome expects, what our DNA expects. This mismatch is the central player in these degenerative conditions.
We can't, right now, effectively change our genome, but we can change certain factors in our environment: the food we eat, the sleep that we get, the activities in which we engage, the level of stress in our lives, the amount of time that we spend enjoying nature. All of these are important variables that will take us back and rekindle a better relationship with the gift of our inheritance.
Robbins: There is a lot that is terribly wrong with the American
diet, and it seems to have been getting worse for years now. Fifty years ago, the consumption of high fructose corn syrup in the
United States was effectively zero. Today, high fructose corn syrup represents nearly half of the enormous amount of caloric sweeteners consumed in this country.10 I'm sure people know that drinking sugar-sweetened beverages, like soda pop, for example, but also flavored teas and sports drinks and so forth are not healthful. But what about fruit juice? I'm not talking about eating whole fruit right now, which contains fiber. But, do common fruit juices, like apple juice and orange juice, have an effect on our uric acid levels?
Dr Perlmutter: Dramatically. There's nothing natural about a glass of organic, freshly squeezed apple juice, orange juice, you name it. When in our history did we suddenly have the ability to suck down 16 ounces of orange juice or apple juice or anything else for that matter? No, we would eat fruit. And as such, we would spread out our fructose exposure over a period of time in the context of dietary fiber that would slow the fructose absorption, in the context of vitamin C that would help with uric acid excretion, in the context of various bioflavonoids that are associated with reduced uric acid production.
So eating fruit is a natural experience. By and large, in a typical apple, we're talking maybe 5–10 grams of fructose along with the other components, the fiber, the bioflavonoids, vitamin C. So fruit consumption, modest fruit consumption, is actually associated with a lower uric acid.
Fruit juice, on the other hand, is a powerful way to suddenly expose your physiology to a glut of fructose that activates liver fat production and is immediately metabolized into uric acid. You know, you can drink a can of Coke, or you can drink that same amount of orange juice or apple juice, and you're getting the same amount of sugar. So you may think it's natural, but I can assure you that our hunter-gather forebears did not suddenly come upon a tree with cartons of orange juice hanging from it.
Foods to help reduce uric acid
Robbins: You mentioned vitamin C. People sometimes go to these juices for vitamin C. I'm thinking about broccoli. It's low in purines, it's high in vitamin C. And I know that people with gout are often told to eat broccoli and other foods that are high in vitamin C because vitamin C helps to reduce uric acid levels in the body.
And there are other foods that are also often recommended to help reduce uric acid. I'm thinking of bananas and apples, cherries, coffee, citrus fruits (whole citrus fruits, of course), and green tea.
Are there any foods you would add to that list?
Dr Perlmutter: The foods you mentioned are wonderful, especially as it relates to broccoli and the other cruciferous vegetables. Though they actually do contain a fair amount of purines, it turns out that — in the context of the vitamin C, of the fiber, of the bioflavonoids — they've long been recommended for gout patients. It's a good choice. There are other things that cruciferous vegetables, especially broccoli, can offer up, (and especially broccoli sprouts), like being able to use the chemicals in broccoli sprouts, the glucoraphanin to allow your body to make sulforaphane which is powerfully anti-inflammatory, upregulates the production of antioxidants in the body. So all the things you said are all good things.
Having said that, it takes us to a place of our metabolism. There are two major pathways in our metabolism. There's a switch, if you will, that controls whether we go down one side or down the other side, is the hunting good or is the hunting worrisome? And we might not have food. Defining the pathways
The pathways are defined by their champions. And the champion of the hunting-is-good is called AMPK or AMP kinase, adenosine monophosphate kinase. When we stimulate AMPK, it sends a signal in the body that the hunting is good, we don't have to make fat, we don't have to store fat. We don't have to increase glucose production. We don't have to raise the blood pressure. Everything's good, we've got plenty to eat.
So you can imagine that we would all really want to light up our AMP kinase, as much as we can. And we do that when we're careful what we're eating, when we're using, for example, quercetin as a nutritional supplement. But perhaps one of the most powerful activators of AMPK is exercise. Who knew? Exercise activates AMP kinase and does great things for us.
The other side of the pathway is something called AMPD, AMP deaminase. That is the get-ready-for-hibernation pathway. That is the pathway that says, “Whoa, we need to make as much fat as we possibly can and store that fat. We need to lock it up. We need to ramp down metabolism so we're not burning as many calories, and we need to make more blood sugar to power the brain.”
So we want to do everything we can to not activate this other pathway, AMP deaminase. It turns out that uric acid decides which way we go. Uric acid turns off AMP kinase and leads to upregulation or enhancement of the get-ready-for-winter, getready-for-hibernation, the AMP deaminase.
Now that we understand that — gosh, it's a really cool piece of the puzzle. And we now understand what goes on in the body of the bear getting ready to hibernate, in the body of the hummingbird getting ready for the epic journey, in the body of the camel getting ready to cross the desert. They're lighting up their AMP deaminase, storing fat, locking it away. And then when they need it, they tap into their AMP kinase, and their metabolism shifts. We wanna keep AMP kinase activated.
You know, that's where the drug metformin works. Metformin is an AMP kinase activator and tells the body, “Stop making glucose.” Turns off what's called gluconeogenesis, the production of glucose in the liver. And that is really helpful for someone with type 2 diabetes because they definitely don't need to be making more glucose. But we can activate that pathway. You don't have to take the drug, you can exercise. Who knew?
Robbins: Well, when you mention Metformin, I think how some clinicians treat high uric acid levels with drugs that limit the amount our bodies can make. Allopurinol, for example, is used to treat gout because it lowers uric acid. And it does that by blocking an enzyme
that is needed to produce the acid. But these drugs invariably have side effects. And with allopurinol, patients get a fever, rash, hepatitis, and kidney problems — serious things. David, do we often have the ability to lower our levels of uric acid without these drugs through simple and straightforward diet and lifestyle adjustments?
Dr Perlmutter: Absolutely. Allopurinol, as you mentioned, does target a very important enzyme that is involved in the production of uric acid. And this xanthine oxidase lends itself very readily to being downregulated or turned off by allopurinol, febuxostat, other medications. But we now understand that certain bioflavonoids and certain naturally-occurring pigmented substances like quercetin and luteolin target xanthine oxidase almost to the extent of allopurinol. And it's really quite remarkable. A profound impact
One study published in the British Journal of Nutrition back in 2016 reviewed a group of 22 young men with borderline uric acid elevation. They were given 500 milligrams of quercetin daily and their uric acid levels fell by 8 per cent in two weeks.11 That's profound.
So when you add the idea of a little quercetin, maybe some luteolin, to a reduction in the consumption of fructose, maybe consider eliminating purine-rich meats like liver and kidney and scallops, well, what that can do to uric acid can be profound.
Is there a place for the use of drugs like allopurinol in the treatment of hyperuricemia or elevated uric acid? There is for people who don't seem to respond to doing all the dietary things on the front end. You know, people who have very high uric acid and may have gout, may have kidney stones, by all means, consider medication under the care of a physician, of course. But for the, you know, all the rest of us who are at risk…
The average uric acid level in America today is 6.0. The risk for cardiometabolic issues is anything above 5.5. The mainstream of medicine will tell you that your uric acid is normal if it's seven or below. But those levels are derived only in the context of gout because it's above seven that the uric acid crystals begin to form. I'm not interested in normal levels, I'm interested in optimal levels. The best we can tell people is to get their uric acid level to 5.5 or lower. By and large, this can be done by lifestyle changes.
Robbins: Well, in some of the studies that I've seen that document the associations between elevated uric acid levels and serious negative outcomes for the brain, the amount of uric acid elevation is actually so slight that the numbers could easily be construed as just the high end of normal, as it's usually understood. I take it this is one of the reasons you recommend lower limits for uric acid levels than the current guidelines propose.
Dr Perlmutter: That's right. And my hope is that mainstream health care revisits the notion of what defines a good uric acid level, not just what's normal. Because, as you and I know, normal is another way of saying average. And the normal range is having a standard deviation or two away from the average and saying, “Well, that's gonna be close enough.”
My gosh! That's not good enough for people these days. People — I don't wanna be average. I mean, the average health in America is not too swift, so I wanna be optimised. And that's been your mission for so many years — the notion of having the ability to have the tools, meaning the knowledge, to achieve optimal health.
Robbins: Well, it has. And I appreciate so much what you're saying here about the importance of uric acid levels and how we have normalised a level that's actually too high. I mean, it may not cause gout, but it's causing a lot of serious problems. And we now have studies finding that people who are admitted to a hospital with a
COVID-19 infection and who also have elevated levels of uric acid are 2.6 times — almost triple — more likely to end up in the ICU on a ventilator or dying, compared to those who are admitted to the same hospitals with the same COVID-19 infections, but who have normal, truly normal uric acid levels.12
Late last year, a Harvard study was published in the medical journal, Gut. The study followed 600,000 adults for nine months and found that people who ate more fruits and vegetables and legumes had a 9 per cent lower risk of getting COVID-19. And if they did get the disease, the people eating more fruits and vegetables and legumes had a 41 per cent lower risk of developing severe
COVID.13 David, could you help us understand why this is the case?
Dr Perlmutter: Well, I can. And I think the early information that we got as related to bad outcomes from COVID, (“bad outcome”, being defined as admission into the intensive care unit, being put on a ventilator, and death is certainly a bad outcome) was related to the metabolic issues we've been talking about. In other words, your risk of a bad outcome from COVID is dramatically increased if you are overweight significantly or hypertensive, type 2 diabetic. I lost a very close friend. A type 2 diabetic, a general surgeon, died of COVID.
So we've known that. And you would expect, if uric acid is opening the door to these metabolic problems, then perhaps there would be an increased risk of having this outcome based upon having elevated uric acid. And in fact, several studies have shown that, as you well described, the risk of going on mechanical ventilation increased threefold, put in the intensive care unit increased at least twofold, risk of death also increased. Several Chinese studies have confirmed to us that uric acid is a player here, that it is inducing these metabolic problems, which bode poorly for outcomes, as it relates to this particular infection.
It would indicate that the outcome from various types of infections or other health challenges would be worse if a person is metabolically dysfunctional. But one wonders, even taking it further, could there be any immune compromise in relation to uric acid elevation? Well, let me propose to you that because uric acid leads to these metabolic issues and these metabolic issues are associated with problems of what is called cellular senescence — the aging of our immune cells — that connection is very straightforward and very simple to understand. So our immune response, our ability to defend ourselves with the activity of our white blood cells is severely compromised in patients with metabolic issues. Uric acid is a central player as defined in 2016 in terms of metabolic dysfunction.
Alcohol and uric acid levels
Robbins: There are many good reasons to make sure that our uric acid levels are in check. And it's also important to acknowledge that consuming alcohol powerfully raises our uric acid levels.
Some might be wondering about their alcohol intake. If someone is serious about reducing their uric acid levels, what would be the ideal amount of alcohol they should consume?
Dr Perlmutter: More important than the amount would be the type. It matters what you drink.14 Hard liquor, is associated with a pretty significant increase of uric acid. If you drink wine and you're a male, the indication is it won't have much effect. And if you drink wine and you're a female, there's a slightly lower uric acid.
Beer is the worst offender. It is metabolized like fructose. It's exquisitely high in purines. because of the yeast and yeast means a lot of nucleic acid metabolized into purines. It dramatically raises uric acid levels, telling the body to make fat. We now have a good understanding of where the beer belly comes from.
What is the science that supports our understanding of this? Many of the studies I've quoted here come from the Japanese literature. Japan is way ahead in understanding the relationship of elevated uric acid to metabolic health issues. Interestingly, in Japan, they now have a purine-free beer for people watching their uric acid levels. How incredible - an understanding of the literature, understanding of the science, then capitalising on it by creating a purine-free beer.
