We’ve all had those stressful days at work. From the moment you first check your email, probably before you even get out of bed, everything you had planned for your entire day slips away from you. You spend hours at work putting out fires and dealing with irascible people. You know your performance is slipping with each unfortunate task, but there’s no choice except to push through.
At the end of the day, you feel ineffective, exhausted, and at your wits’ end. You realize you never ate or left your work-from-home space except to use the bathroom. You flop on the couch, stare at the ceiling, and hear your heart racing as you wait for your brain and body to calm down. As you lie there, you start to think of dinner and a bottle of wine—a glass just isn’t going to cut it. In the kitchen, you open your pantry and try to decide what to eat. You see a box of instant mac and cheese, but you’ve been trying to lose weight and you know you shouldn’t eat a huge bowl of refined carbs and fats.
Just when you’ve made up your mind to eat a healthy salad, a text pings on your phone. It’s your boss, asking if you can jump on a call an hour later. No explanation, no assurances that everything is okay. Your mind shifts into overdrive. What is this about? It must be something important. What news could be bad enough that it can’t wait until the next day? Are you being fired? Is corporate folding your department and laying everyone off? Even if there’s no reason for panic, you’re sick of how virtual work means there’s no cutoff when you leave the office at five p.m.; work extends into all hours with no boundaries.
You look at the clock. An hour isn’t much time, but suddenly it feels like an eternity, leaving your mind to stew about what your boss could want. At least you have some time to eat. You turn back to the pantry, but now eating responsibly doesn’t feel like a priority. Out comes the mac and cheese, a baguette you can soak in garlic butter, and for good measure, a frozen pizza that you bought just because it was on sale. Before you know it, you’ve wolfed it all down, just in time to hear the ping of a text on your phone, causing your anxiety to spiral again. Your boss is ready for that call.
What went wrong? You were completely aware that you were making bad food choices, but suddenly, it was as if your brain had lost its ability to listen to reason, and something more instinctual took over. Part of the answer might be purely practical: you might rationalize to yourself that you only ate the junk food because it was easier or more convenient than healthier options. But there is another basic truth: stress and anxiety make you crave food, especially high-calorie, carb-, fat-, and sugar-laden comfort foods, which feel satiating in these moments. After all, they’re called comfort foods for a reason, and scientific studies have confirmed that eating sugary, fatty food can lead to short-term improvement in mood during difficult emotional times.1
Medical researchers have studied that association through the study of a hormone called leptin. Since its discovery in 1994, leptin has become a centerpiece of research into our appetite, a vital link in understanding how our bodies and brains tell us when we are hungry and what to eat. The most recent research also points to leptin as another factor in the strong connections between anxiety and the food we eat.
Leptin is a hormone secreted by white adipose tissue, the medical term for the type of tissue that makes up most of an adult human’s fat reserves. Though adipose tissue gets demonized in popular culture, a healthy human body requires a significant percentage of body fat to function properly. We used to think of adipose tissue as being largely inert, its purpose to insulate against cold temperatures and store excess calories, but recent research indicates that it’s actually a full-fledged endocrine organ that secretes hormones that affect the entire body.2 Leptin is one such hormone, and its main function is to signal to the brain when you’ve had enough to eat by inducing feelings of fullness, or satiety.
At its most basic, leptin acts as a kind of thermostat for your body’s long-term energy-storage needs. Elevated levels of leptin reduce your appetite, and low levels of leptin increase your appetite. Therefore, if you have more adipose tissue—and therefore greater energy stores—more leptin is produced, telling your brain that you don’t need to eat to excess. If you have less adipose tissue, less leptin is produced, signaling to your brain that your body needs to prioritize finding sustenance or risk starvation.
In performing this long-term management of fat stores, leptin also influences the amount of food you eat in a sitting, and even the type of foods you crave, particularly during stressful times. A variety of studies have shown that leptin levels are decreased following acute stress, which means that when you’re stressed or anxious, your brain struggles to get the signal that you’ve had enough to eat.3 Furthermore, studies have shown that lower leptin levels correlate with an urge to eat comfort food and that increased leptin during stressful times correlates with lower intake of comfort food.4 And to complicate things even further, an overabundance of leptin as a result of being overweight can overwhelm leptin receptors, creating a condition called leptin resistance, which causes leptin to malfunction even when there is plenty to go around, making it even more difficult to change patterns of overeating.5
Given its key role in regulating appetite and food cravings, it’s easy to see how disruptions in leptin can wreak havoc on the best-laid eating plans. And even beyond its core roles, science has uncovered more and more ways that leptin influences the body. We are now beginning to understand that leptin is a true head-to-toe hormone that has influence on the cardiovascular system, gastrointestinal system, renal system, immune system, and connective tissue.6 But most significant is leptin’s effect on your brain, which illustrates another key connection between food and anxiety.
Building on everything we’ve learned so far in this book, it’s not hard to predict the ways in which overeating, particularly binging on fats and sugars, can increase your anxiety—such a diet could very well lead to the kind of gut dysbiosis we learned about in chapter 2, which could upset the balance of brain chemistry, cause immune disruption as we saw in chapter 3, and lead to chronic inflammation as we saw in chapter 4. Once again, we see that all these systems are so tightly tied together that it can be difficult to pinpoint the exact cause of the problem.
But in addition to being a factor in poor diet choices, there is also growing evidence that leptin disruption could be directly involved in causing anxiety as well, because of how it affects the brain. Leptin’s work to manage fat stores and regulate appetite involves a complicated signaling process that entails circulating from fat cells through the body as it monitors energy stores, and then transmitting that information to the brain to give instructions for regulating appetite. This information transfer in the brain happens via the brainstem, hypothalamus, and amygdala.10 Remember from chapter 1 that the hypothalamus and amygdala are anxiety hot spots, controlling processes like reward and motivation, fear response, and fight-or-flight response.
Many studies have shown that proper leptin function has a calming effect on these parts of the brain, helping to alleviate anxiety. For example, animal studies have shown that increased leptin levels lead to a reduction in anxious behaviors on par with the results of the common antianxiety drug fluoxetine (Prozac).11 Similar results have been found in humans, with studies in both men and women confirming that higher leptin levels correlate with lowered anxiety.12
On the other hand, lower leptin levels have been associated with a variety of anxiety disorders. For instance, in a study of patients suffering from panic disorder, subjects who had low leptin levels were more likely to suffer from panic attacks than those with higher leptin levels.15 Low leptin levels have also been associated with GAD in men.16 A similar association has been shown in patients suffering from obsessive-compulsive disorder and depression.17 Animal studies have even suggested that leptin has the potential to reverse social anxiety, inducing greater trust and social interaction in mice.18
Since leptin is a compound produced inside your body, it’s a challenge to “add more” via your diet. Still, if low leptin levels are causing issues with appetite and mental health, certain diet and lifestyle changes have been shown to increase leptin levels. For normal-weight individuals who are not leptin resistant, the best diets to follow are those high in healthy omega-3 fats, low in refined carbs and sugar, and full of fruits and vegetables. For instance, the Mediterranean diet, which we’ll discuss in detail in chapter 11, is a great choice.
Thus far we’ve learned that leptin has an inverse relationship with anxiety: higher leptin means lower anxiety, and lower leptin means higher anxiety. While this association is true in most cases, it doesn’t tell the whole story. In some cases, high serum leptin—that is, a large amount of leptin in your blood—can actually correlate with higher anxiety.
This positive association between leptin and anxiety is usually found in patients who are obese or otherwise struggling to control their appetite. For example, one study tracked leptin levels of breast cancer patients who were also suffering from anxiety. Out of two hundred participants, obese participants’ leptin levels spiked more dramatically when they were anxious, which wasn’t the case for nonobese subjects.19 Another study showed that young people ages ten to sixteen who struggle to control their appetite also showed a positive relationship between anxiety and high serum leptin.20 Several other studies have demonstrated that post-traumatic stress disorder is associated with a heightened risk of obesity and also higher serum levels of leptin.21 And the fact that so many psychiatric drugs increase weight gain as a side effect exacerbates the leptin–anxiety problem.22
High levels of leptin are particularly associated with cases of “somatic anxiety,” anxiety that manifests as physical symptoms without the accompanying mental symptoms. I once had a patient named Marguerite, a fifty-five-year-old single mother who had gone to her primary care physician because she’d been suffering from episodes of rapid breathing that appeared out of nowhere. She was overweight but otherwise healthy, and there was no obvious cause for her symptoms. After a battery of tests such as an electrocardiogram, lung X-rays, and blood work all came back clean, her primary care physician brought up the possibility that anxiety was causing her symptoms. Marguerite was understandably skeptical—she had never felt anxious before, and she hadn’t noticed any obvious changes in her mental health alongside her breathing problems—but she agreed to see me to explore the possibility.
I explained to Marguerite that even if she didn’t feel anxious, anxiety symptoms are expressed through the body (“somatic” means related to the body, distinct from the mind). They manifest as physical symptoms like the hyperventilation she was experiencing, as well as heart palpitations, frequent urination, dry mouth, and excessive sweating. We discussed how somatic anxiety can result from high leptin levels, and Marguerite decided to pursue a serum leptin test. As we saw with inflammation tests in chapter 4, leptin tests aren’t generally performed clinically, so they are rarely covered by insurance, and most hospitals and laboratories aren’t equipped for them. But Marguerite found a private provider and paid out of pocket for her test, which came back showing high leptin levels. Along with her symptoms, that was a strong sign to me that Marguerite was suffering from a condition called leptin resistance.
She changed her lifestyle over the following months to bring her leptin levels under control. Though she made a number of dietary changes, like emphasizing omega-3 fats over omega-6-rich vegetable oils (we’ll talk more about different types of fats in part 2), the key for her was eliminating sugar. She had already cut down on obvious carbs, like bread and pasta, but she also had to be aware of the kinds of excess sugar that can lurk in sauces, salad dressings, and drinks. Once her diet was straightened out, Marguerite stopped hyperventilating, lost weight, and regained control over her life.
Why does leptin have such a seemingly contradictory relationship with anxiety? Is it really a Goldilocks situation where your brain needs precisely the right amount, with both too little and too much triggering anxiety? Not exactly.
Understanding these complicated relationships hinges on understanding the nuances of how hormones work in your body. For a hormone to be effective, your body requires two things: enough of the hormone to send the message and a properly functioning receptor to receive the message. That creates two possible ways in which the system can go awry. If your body isn’t producing enough leptin, serum leptin levels stay low, and the lack of leptin in your brain can cause anxiety. But when you’re overweight or obese, you naturally produce a lot of leptin—since leptin is manufactured and secreted by adipose tissue, an excess of adipose tissue means an excess of leptin. With too much leptin in your brain, your leptin receptors can malfunction and lose the ability to respond. Therefore, your brain can still be running a functional leptin deficit even as your endocrine system is continually pumping more into your brain, without being able to rectify the problem. Hence, your brain can still slip into anxiety even though your serum leptin levels are abnormally high.
This inability of your leptin receptors to function properly is called leptin resistance. It’s similar to another major metabolic concern, insulin resistance, which we’ll discuss in more detail in chapter 6, where the body loses the ability to respond to the hormone insulin, resulting in elevated blood sugar, which can lead to type 2 diabetes. In fact, leptin resistance and insulin resistance are so often found together that researchers speculate that the two may be causally linked.23
Leptin resistance puts both your body and mind in a difficult spot. Without being able to register the mediating presence of leptin, your brain doesn’t know when to rein in your appetite or how to stay away from eating unhealthy foods that dial up more destruction, magnifying your anxiety in a variety of different ways. Treating leptin resistance is even more complicated than treating low leptin levels—after all, it’s not a matter of increasing or decreasing your serum leptin; it’s about retraining your body’s leptin receptors to function properly.
Happily, it is possible to reset your leptin sensitivity through dedicated lifestyle changes, as we saw with Marguerite. Animal studies back this up: when obese rats who showed severe leptin resistance were put on a healthier diet, they fully regained leptin sensitivity.24 Food choices for restoring leptin sensitivity are similar to those we discussed earlier for maintaining healthy leptin levels, such as the foods included in the Mediterranean diet. But research has shown that fighting leptin resistance is also about when and how much you eat. A variety of fasting and calorie-restrictive diets have been shown to be effective at helping to fight leptin resistance, but before trying any kind of radical diet, you should consult a professional, working to create an eating plan that is safe and healthy.25
If you are overweight and suspect you might be suffering from leptin resistance, the first thing to try is cutting out sugar. Several animal studies have established that a high-fructose diet causes leptin resistance in mice, regardless of the diet’s fat content, and that when the mice were taken off the high-fructose diet, leptin sensitivity returned.26 High-sugar meals have been shown to significantly increase leptin levels in overweight individuals, especially when that sugar comes from sweetened sodas.27 Weaning yourself off sugar is a great first step toward resetting your relationship with leptin, improving your metabolic health, and lowering your anxiety.
The difficulties of identifying, understanding, and treating leptin resistance are a good reminder that the factors that drive anxiety and struggles with your weight often have nothing to do with willpower. If your brain is unable to benefit from the calming effects of leptin on both your mood and appetite, that’s not a moral failing or something to be ashamed of. It’s simply a chemical issue in your body that can be rectified with knowledge and effort. That isn’t made any easier by living in an era when unhealthy food is cheap and available at every turn, but with patience, proper planning, and fostering a love for whole, healthy foods, it’s absolutely possible to take control of your diet and mental health.
In its management of fat stores and regulation of appetite, leptin has an important effect on your body’s metabolism, the vastly complicated machinery that ensures you have the energy you need to live. Just as leptin dysfunction causes mental health symptoms, an off-kilter metabolism is one of the greatest risk factors for anxiety.