The Acid Test

IF YOU WERE LOOKING FOR Tom Wolfe’s follow-up to his counterculture classic from the 1960s about adventures in psychedelic drug use, you’ve come to the wrong place. The acid we’re talking about in this book is of an entirely different type, one that has everything to do with being in control of your health and feeling empowered to live a full, long, and vibrant life with a fit body and sharp mind to the very end. You may have never heard of uric acid before or put any serious thought into this metabolic compound aside from perhaps its role in gout and kidney stones. And if that’s the case, there is no fault on your part, because this has been the messaging for years. Get ready: I’m going to give the term drop acid a whole new meaning. Your body and brain will thank you for it.

In the fall of 2020, as the COVID-19 pandemic continued to rage across the world, I was on a run outside listening to one of my favorite podcasts: Dr. Peter Attia’s The Drive.¹ I always get a lot done while running; it’s as much exercise for my mind as it is for my body and brain. On this particular day, Dr. Attia’s guest had a deep impact on me. Dr. Richard (Rick) Johnson, a professor of nephrology at the University of Colorado, was basically providing a master class on uric acid, revealing the stunning connection between this little-known, underestimated metabolite in the body and overall metabolic health—as well as its downstream biological effects, which can influence virtually every condition and ailment you can imagine. Uric acid is often described as a harmless inert “waste product” of metabolism that is normally excreted in urine (and in stool, though to a lesser extent). It is cast as a trivial, incidental by-product of our normal biology. But it is anything but meaningless or unworthy of our attention. It sits at the heart of regulatory mechanisms involved in our most fundamental processes of metabolism. And it is these processes that, when they go awry, end up manifesting themselves as the most pervasive health issues of our time—from obesity and insulin resistance to diabetes, elevated blood fats, hypertension, cardiovascular disease, and even cognitive decline and dementias.

The following day, I listened to the podcast again. The message and the data behind it were so compelling that I immediately started to take notes and do my own deep dive into the scientific literature. That’s when I fell down the proverbial rabbit hole, albeit a satisfying and illuminating one. Dr. Johnson is one of many scientists around the world researching the role of uric acid in our lives—especially in light of modern diets riddled with uric acid–stimulating ingredients. My own research led me to pose a simple question that has an eye-opening answer.

Q: What do obesity, insulin resistance, diabetes, nonalcoholic fatty liver disease, hypertension, coronary artery disease, stroke, neurological disorders including Alzheimer’s disease, and premature death have in common?

A: High uric acid levels.

My exploration into the science of uric acid finally answered many questions that had remained in my mind for years. Yes, we know that sugar can threaten health, but how? Why do so many people stick to stringent diets and yet still have problems controlling their weight and blood sugar and go on to develop serious illnesses? Why are rates of high blood pressure going up, even in adolescents and in people who maintain an ideal weight (a staggering one in three adults has hypertension and one in ten youths between the ages of twelve and nineteen has elevated blood pressure)?² What is the connection between the sugars added to approximately 74 percent of the foods and beverages sold in America’s grocery stores and the ever-increasing rates of chronic degenerative diseases, including those that rob people of their mental faculties?³

You’re about to find out.

If you’ve tried everything to gain control of your health but still feel like you can’t reach your goals, I think you’ll appreciate what I have to say. When you discover what I’ve learned down this rabbit hole, you’ll be immediately empowered. This book, part personal journey and part medical investigative reporting, is the culmination of my efforts. I don’t want the science screaming from the literature to take decades to reach everyone in their doctors’ offices (as it usually does, to the tune of nearly twenty years). I have taken this new knowledge seriously and adjusted my own habits to ensure that I maintain my uric acid level within a healthful range. It’s not that difficult and will be incredibly beneficial to your vibrancy and longevity. For an apt analogy, think about the story of smoking and the ills of even secondhand smoke. Until enough people convincingly proved the link between tobacco and cancer, we were tolerant of the habit. Even those of us who never smoked didn’t become overly concerned when the air filled with fumes in bars, restaurants, and airplanes. But now look at how we perceive smoking.

Managing uric acid levels to achieve radiant health is a strategy that’s been validated by science for decades. But it remains a blind spot in general medicine today. I’m about to equip you with a new pair of glasses that will give you a totally new perspective about what it means to be in—and to achieve—robust health.

HIDDEN HISTORY

More than a century ago, Scottish physician Alexander Haig sounded the alarm about the connection between uric acid levels in the body and conditions as diverse as migraine, depression, epilepsy, diabetes, obesity, liver disease, high blood pressure, cardiovascular disease, stroke, cancer, dementia, and rheumatism. His revolutionary findings, which culminated in a book published in 1892 and a subsequent review of the fourth edition in 1898 in the Journal of the American Medical Association, did not travel far into the next century.⁴ Although prescient, they were too forward-thinking for the era. Thereafter, uric acid continued to be dismissed as an inert waste product of cellular metabolism that at high levels could cause kidney stones and a form of arthritis called gout. But for most people who never develop gout or kidney problems, uric acid was thought to be an innocuous biological compound undeserving of any scrutiny.

In gout, which is considered a metabolic disease, excess uric acid erodes bone tissues and forms sharp, needlelike mineral crystals (urate) in the joints, which causes inflammation and pain, sometimes severe. Gout notoriously strikes the bunion joint in the big toe. From kings and queens to poets, scientists, and explorers, history is home to many famous gout sufferers, including Alexander the Great, Charlemagne, Henry VIII, Christopher Columbus, Leonardo da Vinci, Isaac Newton, John Milton, Queen Anne of Great Britain, Benjamin Franklin, and Alfred, Lord Tennyson. Although gout is more common in men, the rate evens out a little more after women hit menopause.

From the 1960s to the 1990s, the number of gout patients more than doubled in the United States, and it has continued to rise—affecting nearly ten million people.⁸ It’s one of the most common inflammatory and immune-system diseases of our era.⁹ And how interesting that the prevalence of obesity and metabolic syndrome has also increased in lockstep with gout. These surges parallel the upswing in the consumption of the very ingredients that cause hyperuricemia (elevated uric acid) and gout: sugar-sweetened foods and drinks, including soda pop and fruit juice (and, yes, the much-beloved orange and apple juices).

But again, this conversation about uric acid isn’t just about gout. An estimated 21 percent of the population in the United States lives with hyperuricemia, putting them at risk for a host of health challenges.¹⁰ That’s roughly one in every five individuals. And the vast majority of these people don’t know it because they don’t have gout or kidney issues. (While a test for uric acid levels is commonly included in the general blood work many of us have done as part of an annual physical, it’s safe to say that patients and their physicians rarely pay attention to the result.) In fact, there is a term I’ll discuss at length called asymptomatic hyperuricemia—high uric acid levels with no adverse symptoms to show for it. It’s important to note that the only adverse symptoms included in this medical definition are gout and kidney stones. But asymptomatic hyperuricemia is far from innocent or just an early signal of gout or kidney problems. As you will soon learn, long before any symptoms develop, asymptomatic hyperuricemia may well be fomenting an unending, irreversible storm and subtly stoking biological processes that ultimately result in elevated blood sugar and blood pressure, bad cholesterol, excess body fat, and systemic inflammation, which opens the door for any number of chronic degenerative conditions. Put simply, hyperuricemia precedes these debilitating ailments that become difficult to manage once they take root. And, incredibly, in our distant evolutionary past, elevated uric acid served as a survival mechanism, as I will soon explain.

Only in the past two decades have research scientists revisited Dr. Haig’s discoveries and confirmed that he had indeed identified what has turned out to be a central mechanism in many preventable maladies. Today’s medical literature is exploding with evidence that elevated uric acid levels are the bellwether of many ills, such as type 2 diabetes, excess weight and obesity, and hypertension, to name just a few. What’s more, some clinicians are now specifically treating elevated uric acid with pharmaceuticals as a way of bringing these conditions under control. But as you will learn, we have the ability to lower our levels of uric acid with simple, straightforward lifestyle adjustments, almost always without having to resort to drug interventions.

For years now I’ve repeatedly turned to the best medical literature from around the world to figure out why our rates of these diseases have continued to skyrocket. Sure, our diets and lifestyles have changed, but I felt there was a missing piece to the puzzle. And what finally leaped out from the pages of the most leading-edge journals is undeniable evidence that these challenging conditions are the end product of the connection between our modern lifestyle choices and uric acid. Uric acid is a key central player that we need to understand. Much as we learned in the twentieth century that C-reactive protein tells us about the body’s level of systemic inflammation, which is linked to many of the diseases that afflict us today, we are discovering in the twenty-first century that uric acid levels are associated with dysfunction and disease in the long term. We all need to keep weight, blood sugar, and blood pressure in check, and the same goes for uric acid. Uric acid is not a minor idle character in the story of our body’s chemistry. It’s a perpetrator of ill health when it’s not well managed.

Unfortunately, most physicians are not yet attuned to this new knowledge—knowledge that tells us, according to one landmark scientific paper published by the American College of Rheumatology, that elevated uric acid is responsible for 16 percent of all-cause mortality and an astounding 39 percent of total cardiovascular disease.¹¹ (All-cause mortality refers to death from any cause.) In a compelling review published in 2017, investigators wrote: “An elevated serum uric acid [level of uric acid in the blood] is also one of the best independent predictors of diabetes and commonly precedes the development of both insulin resistance and diabetes type 2, as it was discovered that one quarter of diabetes cases can be attributed to a high serum uric acid level and elevated serum uric acid levels were found to be closely associated with insulin resistance and diabetes mellitus type 2.”¹² They went on to write that “serum uric acid is a strong and independent risk factor for diabetes in middle-aged and older people.”¹³Independent risk factor is a term you will hear repeatedly. It’s a phrase that research scientists use to define a certain circumstance or measurement, in this case uric acid level, that on its own corresponds to harm or injury to the body. As I’ll explain, a person with a heightened uric acid level who has no other risk factor for type 2 diabetes (e.g., obesity) can indeed develop diabetes at a healthful weight because of uric acid’s sneaky shenanigans.

Without a doubt, the overwhelming contributor to elevation of uric acid in our modern world is the cheapest, most abundant ingredient around—it’s the kind of sugar we’ve been told is relatively “safe” because it doesn’t directly raise blood sugar: fructose.¹⁴ And I’m not vilifying fructose from fresh whole fruits. I’m talking about the refined, highly processed fructose that finds its way into many of our daily provisions, including our beloved salad dressings, sauces, condiments, baked goods, snack and energy bars, packaged foods, beverages, and foods you wouldn’t even think contain sugar. You probably have a general sense that high-fructose corn syrup isn’t good for you, but you don’t realize how pervasive this ingredient has become and that you can consume too much fructose by eating other forms of sugar. The science showing fructose’s true colors has only been elucidated in the medical journals over the past decade or so—and it doesn’t concern what your grandmother knew as fructose. Although the prestigious medical journal The Lancet reported on fructose-induced hyperuricemia in 1970,¹⁵ in the years since then we’ve come to understand the full range of fructose’s adverse effects.

It’s not news that sugar-rich diets are linked to all kinds of health problems. But we haven’t been told the why and how of sugar’s devastating blow to our bodies, especially as it relates to fructose from nonnatural sources. We now understand fructose’s biological mechanisms and its veiled relationship with uric acid, both of which help explain the root causes of these intractable conditions—and this is not merely a flimsy association. In fact, evidence from human and animal studies indicates that the connection between dietary sugars and obesity is probably driven primarily by the metabolic effects of fructose.¹⁶ The way the body handles fructose involves uric acid and directly favors the development of obesity.

The other main culprit that leads to elevated uric acid levels is a class of chemicals called purines, which are found in all living cells and contribute to healthy physiology but, like body fat, are problematic in excess. Purines are organic compounds that cells use to make the building blocks of DNA and RNA, and when purines are naturally broken down by the body, uric acid is formed. Because purines—two of which, adenine and guanine—provide the backbones, or nucleotides, for DNA and RNA formation, anything that has to do with tissue (cellular) breakdown will raise uric acid levels. As damaged, dying, and dead cells are degraded, purines are released and turned into uric acid during the process. Purines are also constituents of other important biomolecules, such as the energy giant ATP (adenosine triphosphate) and the coenzymes we need for the biochemical reactions that sustain life.

Purines are more common than people realize. In addition to being naturally produced by the body during cellular turnover, they are abundant in a wide array of foods, including certain seafoods, meats, multigrain breads, beer, and even some legumes and vegetables. As these external sources of purines are processed by the body, uric acid is synthesized mainly in the liver, intestines, and inner cellular lining of blood vessels (what’s called the vascular endothelium). Their prevalence in what we view as rich, lavish fare fit for the wealthy is why gout has long been known as the “king of diseases and the disease of kings.”¹⁷ But purines also lurk in many foods touted as healthful in popular diets. During the last decade, large epidemiological surveys have revealed an association between the intake of purine-rich food and the blood concentration of uric acid. Let’s not blame vegetables, however, because as we shall see, despite the fact that certain vegetables (e.g., cauliflower, spinach, and mushrooms) might be rich in purines, they may not trigger an increase in uric acid.¹⁸

For half a century, low-purine diets have been prescribed for people prone to gout and kidney stones. But this dietary protocol is increasingly recommended for anyone looking to control uric acid and rein in the body’s metabolism. Just because you don’t develop gout or kidney stones, conditions that can have genetic origins as well, doesn’t mean you won’t suffer from the consequences of chronic high uric acid.¹⁹ Our understanding of this compound we all have coursing through us provides vital clues to unlocking the mystery of optimum human health.

For people who have gone on every “doctor-approved” diet to little or no avail, targeting uric acid fills in a giant blank in the equation. If you don’t factor in the uric acid component, going low-carb, vegan, keto, paleo, pescatarian, lectin-free, or even Mediterranean might not be enough to help you permanently drop excess weight or easily manage both blood sugar and blood pressure. Moreover, this new science calls for a revision of the way we reference the glycemic index and consume certain so-called healthful foods. Uric acid levels can generally be brought into balance by (1) implementing simple dietary tweaks, (2) getting quality sleep and adequate exercise, (3) minimizing the intake of uric acid–increasing drugs, and (4) consuming acid-reducing gems such as tart cherries, coffee, vitamin C, and quercetin (the last two are found in many foods and can be taken in supplement form). Nurturing the microbiome is also vital to controlling uric acid; studies reveal correlations between elevation in uric acid and significant increases in the types of bad bacteria in the gut that are associated with inflammation. I call the protocol outlined in this book the LUV Diet—using an acronym for “lower uric values.” In this book, you will learn how to both lower uric acid levels and maintain ideal levels once you’ve achieved them.

My research taught me things my medical education decades ago—and my experience in all the years since, working as a neurologist treating patients—never did. One important reason I became a physician to begin with was my own curiosity. Curiosity plays a key role in why I do what I do. I like to live on the edge of wonder, continually asking: Why do patients develop the problems they do? And once we unravel these mysteries, how might we change what we do as physicians so we can better serve our patients? For me, it has never been enough to simply treat the symptoms of a problem—for example, using a drug to lower blood pressure or balance blood sugar. I want to understand the root of these problems and so many others, then address the causes, not just the manifestations. As I have been fond of saying for many years, I’m really interested in focusing on the fire, not just the smoke.

THE NEW BELLWETHER OF HEALTH

Despite the publication of Dr. Haig’s work more than a century ago, only since 2005 or so has uric acid finally been viewed as anything more than a risk marker for gout and kidney stones. Scientists around the world are confirming, in study after study, the fact that uric acid factors into our health. In Japan, controlling uric acid has already entered the mainstream practice of medicine quite apart from solely treating gout. I’ve learned a wealth of surprising and empowering information in my quest to understand the role of uric acid in our lives. For example, elevated uric acid levels directly lead to increased fat storage, and there’s a reason for that, dating back millions of years, which you’ll soon come to grasp (and appreciate). Our primate ancestors needed high levels of uric acid in order to build fat stores that would ensure their survival during times of environmental challenges, such as food and water scarcity.

But we all know that food scarcity is not a modern reality for most people living in developed nations. In the pages that follow, I will explore the idea that we humans have acquired genetic mutations that cause us to experience elevations in our uric acid far in excess of those in our ancestral primates, who did not carry these genetic mutations. (Our uric acid levels far exceed those in other mammals, too.) By making early humans increasingly fat and insulin-resistant, uric acid proved life-sustaining. I will examine how this powerful survival mechanism led to passing on these genes to future generations as they allowed us the ability to persevere and procreate. We will then see how environment and evolution butt heads today, when we live in a time of caloric abundance, and how these genetic mutations are now proving so devastating to our health. It’s a fascinating story that ultimately empowers us to rein in our insulin sensitivity, blood pressure, fat production, and even our waistlines and risk for all manner of illnesses.

When the original research on the role of uric acid in diseases other than gout and kidney stones began to appear, as expected, mainstream medicine cast it off as folly. We have now reached a point where this thesis has gained considerable traction and is being explored globally because of its potential to affect the major health issues of our time, including obesity, diabetes, cardiovascular disease, hypertension, and other chronic inflammatory, degenerative conditions. This message is one we all need to hear if we’re to live longer, fitter, and healthier lives and avoid life-crushing conditions that are wholly preventable.

SELF-ASSESSMENT: HOW TO SPOT THE U-BOMB IN YOUR LIFE

Don’t know what your uric acid (UA) levels are? You’ve surely been tested routinely in the past and can actually test yourself at home, just as you would check your blood sugar, weight, or temperature. Even if you have a sense of your UA level, which is of course a dynamic number that changes throughout the day, it’s important to know generally what factors into that level—from what you consume to which medications you take and even how well you sleep and how much you physically move. Before we delve into all the dazzling science behind uric acid’s role in your life, let’s start with a simple questionnaire that reveals what habits could be silently harming you right now.

Respond to these statements as honestly as possible. Don’t think about the connections to sickness implied by the statements; just respond truthfully. In the following chapters you’ll begin to understand why I used these particular statements and where you stand in your risk factors. Note that if you feel like you’re in between yes and no, or if “sometimes” or “rarely” feels like your knee-jerk response, then answer yes for now.

The more yeses you tallied up, the greater your health risks. But don’t panic. Once you gain the knowledge and know-how to rethink your habits, you’ll soon lower your risks dramatically.

Interestingly, a sudden infection, dehydration, excessive exercise, fasting, and crash diets can also elevate uric acid levels in the body. I left these risk factors out of the questionnaire because they typically relate to temporary rises in uric acid and do not reflect the main cause of most people’s chronic problems with it. Nevertheless, I’ll explore all these factors, and for those of you who have been infected by the virus that causes COVID-19, I’ll address your issues directly in the first chapter, given that you may carry unknown risks to your future health that require special attention. Later in the book, I’ll teach you how to understand your UA values and offer target numbers that totally redefine the reference range—the way doctors determine the difference between normal and abnormal.

Being in the normal range is no longer good enough. It’s time we talk about being in the optimal range. You deserve it. You also deserve to know how to rethink other values in your health equation, such as your blood sugar and A1c levels. A test for the latter measures your average blood sugar levels over the previous three months (and is also known as the hemoglobin A1c, or HbA1c, blood test). It’s a commonly used way to diagnose prediabetes and diabetes. But the target numbers your doctor may recommend are not the same ones I’ll prescribe. News flash: brain degeneration begins at a hemoglobin A1c of 5.5 percent, which doctors deem a normal value.²⁰ Even a blood glucose level of 105 mg/dL (milligrams per deciliter), which your doctor might say is fine, is significantly associated with the development of dementia.²¹ No matter what health issues you worry about or currently manage, two fundamental goals to achieve are metabolic health and controlled levels of systemic inflammation. If you don’t know what I mean by these goals, you soon will. And uric acid control helps you find your way to these goals. It’s a gateway to vibrant health.

As this book will show, uric acid is far from a by-product or inert waste product. It’s time to change the dogmatic narrative about this compound, which orchestrates and instigates many reactions in the body. With all due respect to other physicians, I must warn you that your doctor may have dismissed an abnormally high level of uric acid in your routine tests if you don’t have gout or kidney issues. He or she may have said, “Don’t worry about it.” Nothing could be further from the truth. He or she may scoff at the idea that lowering uric acid is an important health goal. Remember, people tend to be down on what they are not up on.

As I’ve stated in the past, we can choose to live our lives, come what may, and hope that modern medical science will provide a remedy for the ills that inevitably develop. But this is a model destined for failure. One has only to look at Alzheimer’s disease, for example, to see that there is no medical treatment for it of any merit whatsoever. Such a treatment would be welcomed beyond measure. But right now we have the science that clearly reveals how making the right lifestyle choices can go a long way toward preventing this untreatable condition. Treating the symptoms of disease—such as lowering blood pressure with medication, reducing blood sugar with medication, and taking drugs designed to help the heart beat more forcefully—doesn’t address the causes of the underlying disease process. Again, this means treating the smoke while the fire is ignored. The goal of this book is to keep you healthy. It is written to equip you with a new, state-of-the-art, deeply validated tool that will soon become a central player among the other implements in your toolbox.

Ready? Let’s get to it!