the precursor amino acid tryptophan is the rarest amino acid in our diet;
ingested tryptophan can be metabolized by an alternate pathway in the body (called kyurenine), which can create inflammatory by-products, leading to worsening of your health;
99 percent of the ingested tryptophan is converted to serotonin in other parts of the body (used for other functions in your gut and blood) before it even gets a chance to be transported into the brain;
tryptophan transport from the blood into the brain is in competition with much higher concentrations of both tyrosine and phenylalanine (the precursors for dopamine) for the same blood-brain transporter;
the serotonin that is manufactured from tryptophan elsewhere in the body can’t gain access to the brain, because it can’t cross the blood-brain barrier;
the serotonin receptors are virtually everywhere throughout the brain, so there’s a big demand for that small supply; and
the enzyme that inactivates serotonin (MAO, the ubiquitous Pac-Man) is very good at its job.
It’s no wonder we’re unhappy: we’re always playing catch-up. Most of us are functionally serotonin-deficient some of the time (a state), and some of us are serotonin-deficient all the time (a trait), both of which can influence clinical depression. There’s barely enough serotonin in the brain to generate even a fleeting feeling of contentment in the first place.
Eating for Sleeping
Serotonin is known to prepare you for sleep1 and influence sleep stage cycles, especially by reducing the active or rapid eye movement (REM) phase and increasing the slow wave or inactive phase of sleep. If you give tryptophan (the precursor to serotonin) to normal non-depressed people, you tend to see some lethargy and sleepiness and decreased reaction time;2 perhaps this is one of the reasons people blame the tryptophan for falling asleep at their Thanksgiving turkey dinner (besides stuffing yourself with stuffing, mashed potato, pumpkin, and pecan pie so that you can’t move). Conversely, if you provide adults with a tryptophan-depleting drink just prior to bedtime to reduce their brain serotonin, their sleep looks like people who have untreated clinical depression, which keeps them awake at night.3 SSRIs, while they treat symptoms of depression, also push the reset button on your sleep cycle, often with the result that you can’t sleep or you sleep too much. Thus, the tryptophan in your diet goes a long way toward determining how well you sleep, and how well you sleep goes a long way in determining your level of contentment. Our increased levels of sugar and caffeine in the diet sure don’t help matters any. We’re wired from Red Bull and Starbucks Frappucinos, making us even less likely to get regular sleep and wreaking havoc on our metabolic systems in general. For instance, a study of fourth and seventh graders shows a correlation between shortened sleep and soda consumption,4 although we can’t determine if this is due to the sugar or the caffeine. More on the role of sleep in unhappiness in Chapter 10.
While there are several steps involved in converting the tryptophan in food into serotonin within the brain, most of us don’t get enough dietary tryptophan in the first place. Eggs and fish have high concentrations of tryptophan, nuts and poultry are not too far behind,5 and spinach and soy make the list as well. Although beware: just because they are advertised as Chicken McNuggets doesn’t mean there’s any chicken in them.6 Indeed, people who are egg eaters and fish eaters have the highest levels of tryptophan consumption as measured by blood concentrations (of course, looking at levels in the blood doesn’t mean that any tryptophan actually made it into the brain, so it’s by no means a perfect marker).7, 8 Fish consumption is inversely related to depression in large meta-analyses,9 although we don’t yet have cause and effect. But eggs are frequently omitted from certain processed foods because they curdle with time, because they can go rancid when not refrigerated or when they’re old, and because enough people are allergic to eggs. And fish is not usually a big seller as an ingredient in processed food, in part because certain fish don’t freeze well and most people want to see the fish to determine how fresh it is.
The nutraceutical industry is actually peddling both tryptophan as well as the next-step chemical intermediate on the way to making serotonin (5-hydroxytryptophan) (see Fig. 7-2) in capsule form. Currently randomized placebo-controlled trials of these nutraceuticals to improve depression are early and limited.10, 11 One group performed a double-blind placebo-controlled trial giving tryptophan to a bunch of petulant people, and lo and behold, they got nicer.12 (Maybe slip some tryptophan in your boss’s coffee tomorrow . . .) A meta-analysis does argue for some benefit in depressed patients,13 with some attendant side effects. However, Big Pharma isn’t interested in going down this road, because a tryptophan pill isn’t patentable, and they can sell SSRIs and charge a bundle. We really don’t know what a tryptophan-replete America would look like.
What’s Your Beef?
What about red meat, which is supposed to provide high-quality protein? America prides itself on its meat production, and its meat consumption. Does red meat have enough tryptophan? It does, but let’s have a look at the difference between the corn-fed beef of processed food versus beef that came from cattle that were grass-fed. Turns out that corn is relatively deficient in tryptophan but is loaded with phenylalanine and tyrosine, the precursors of dopamine.14 While contested by the processed food industry, it is likely that we who eat these animals are not getting very much tryptophan. Furthermore, corn-fed beef has higher levels of branched-chain amino acids (leucine, isoleucine, valine) that contribute to liver fat, which drives the metabolic syndrome (see below). Chicken is the one processed food staple that contains a reasonably high quantity of tryptophan,15 but there’s a big catch. Chickens raised for the processed food industry are corn-fed, just like the cattle, and contain a lot of branched-chain amino acids as well.
Each of these amino acids is “essential,” which means you have to eat them; your body can’t synthesize them. Branched-chain amino acids account for over 20 percent of all the amino acids (building blocks) in the Western diet.16 If you’re in puberty, or a bodybuilder, then these branched-chain amino acids are necessary for building the proteins that are found in muscle (that’s what’s in protein powder). But if you’re a mere mortal like me and most of the sedentary world, then chowing down on excess branched-chain amino acids means there’s no place to store them, which means that the liver has more of these amino acids to process and metabolize into energy. The energy overload in the liver drives fat accumulation and insulin resistance,17 promoting all the chronic metabolic diseases that are part of metabolic syndrome,18 which will directly affect both your physical and mental health.
Metabolic syndrome is the smorgasbord of chronic metabolic diseases from which America, and indeed the entire world, now suffers. To name them: how about heart disease, hypertension, blood lipid problems such as hypertriglyceridemia, type 2 diabetes, non-alcoholic fatty liver disease, chronic kidney disease, polycystic ovarian disease, cancer, and dementia? These are the diseases of insulin resistance, where insulin doesn’t clear glucose from the blood properly, while fat precipitates in your liver and muscles. Next time you’re at the butcher, have him show you strip steak from a grass-fed cow and a corn-fed cow. The grass-fed steak is pink and pretty homogeneous throughout. It’s delicious, but when you grill it up, it’s a little tough. Now look at the corn-fed steak. See all that marbling? We love it, because that’s where the flavor is. And after grilling, it practically cuts with a butter knife. That marbling is fat in the muscle. That’s muscle insulin resistance. That cow had metabolic syndrome; we just happened to slaughter it before it got sick, and now we’re consuming the aftereffects in each and every Big Mac.
What Am I, Chopped Liver?
At the cellular level, the avalanche of energy from a processed food meal overwhelms your liver’s cellular power generators—the mitochondria. When these liver mitochondria get overloaded, they have no choice but to turn the extra energy into liver fat. These m
olecules of liver fat have one of two fates: either (1) your liver can package them into very-low-density lipoproteins (VLDL), which can lead to heart disease and obesity, and which your doctor can measure as serum triglycerides on your lab panel; or (2) your liver can’t package them, they turn into fat droplets, and they make your liver sick. A sick liver doesn’t respond well to insulin, causing the pancreas to release excess insulin. Eventually your pancreas gives out, and now you have type 2 diabetes. You’ve got metabolic syndrome and are losing years of life as your cells and your body age more quickly. How can all this be happening when you’re dieting and buying low-fat products? That’s just what causes it! That’s what’s happened to America, and the world. We lowered the fat and put in more sugar to make our food palatable. And all of that increased sugar in the diet is a leading contributing factor to metabolic syndrome. I wrote a whole book about it (Fat Chance).
People with metabolic syndrome have decreased serotonin function19 and are at very high risk for depression. And not because they’re fat: thin people get metabolic syndrome also,20 with the underlying phenomena of insulin resistance and liver fat;21 they’re called TOFI, or “thin on the outside, fat on the inside.” Furthermore, each of the disease components (e.g., lipid problems, glucose intolerance) correlates with depression even better than abdominal obesity does.22 The foods that drive metabolic syndrome are those that are most clearly associated with the foods that people with binge-eating disorder consume with the greatest avidity: refined carbs and sugar.23 The question is, does the depression drive the food choices, which then drive the metabolic syndrome? Or do the food choices drive the metabolic syndrome that then drives the depression? Which is cause and which is effect? We still don’t know. But what we do know is that some people can eat their way out of both the metabolic disease24 and out of the depression25 by switching to a Mediterranean diet—and why not? Lots of eggs, fish, nuts, fiber, and not very much refined carbohydrate or sugar. The fact that your food choices can lift your mood certainly argues that the food is the driver.
The Slippery Slope
Not only is metabolic syndrome related to depression, it is also related to cognitive decline—and nothing will make you more depressed than losing your intelligence. We’ve known for a long time that people with type 2 diabetes demonstrate cognitive decline26 and that brain insulin resistance correlates with dementia (e.g., Alzheimer’s disease).27 Yet type 1 diabetes—which is a spontaneously occurring disease as opposed to type 2, which is driven in part by the sugar in your diet—doesn’t correlate with dementia. Both forms of diabetes share high blood glucose as the primary phenomenon. But type 1 diabetics are deficient in insulin, while type 2 diabetics have too much insulin but are resistant to its actions. Because it’s not the glucose! It’s the insulin! The insulin resistance, driven by all that excess soda and sugar-laden foods, is what leads to the brain plaques that define Alzheimer’s disease.28
When you’re healthy and insulin-sensitive, the insulin rise from a meal normally tells the brain you’ve had enough food. But once metabolic syndrome sets in, the chronic insulin in the brain does exactly the opposite: it blocks the signal to stop eating.29, 30 Worse yet, the insulin resistance alone (unrelated to blood glucose) predicts cognitive impairment31 and risk for Alzheimer’s disease.32 It’s always been assumed that dementia and cognitive decline are the province of the aged. Not so. Antonio Convit at NYU School of Medicine has shown that teenagers with metabolic syndrome (matched by age, socioeconomic level, school grade, gender, and ethnicity) manifest cognitive decline, brain shrinkage, and decreased white matter integrity.33 And these kids don’t even have type 2 diabetes yet! But they will. In fact, this is a positive feedback cycle. The more brain insulin resistance they develop, the more their dopamine neurons fire, the less restraint of the reward system (your Jiminy Cricket from Chapter 4), the more their anxiety, the less their cognitive inhibition, the more food (especially sugar) they consume, and the more insulin resistance they will develop. Ultimately this vicious cycle culminates in diabetes, dementia,34 and often depression. Indeed, dietary sugar (sucrose, consisting of glucose and fructose)—rather than blood sugar (glucose)—is the driver in this scenario, because dietary sugar underlies insulin resistance, and insulin resistance underlies dementia.35 If you feed fructose to animals, you get all the pathology and cognitive decline one sees in Alzheimer’s disease,36 and it causes changes in genes that predict Alzheimer’s.37 So far in humans, we only have correlation. For instance, sugar consumption correlates with risk for dementia in epidemiologic studies.38, 39 But correlation is not causation. In humans, we still don’t have cause and effect. Does sugar consumption make you lose brain cells, including those that house your serotonin receptors? Or does losing brain cells make you consume more sugar? Both, most likely. But today we just can’t say for sure. Nonetheless, are you comfortable with the risk?
By driving reward, sugar drives risk for addiction (see Chapters 5 and 6), and addiction culminates in unhappiness. Both high-glycemic-index diets (i.e., highly refined carbohydrate from processed foods) and high-added-sugar diets are correlated with depression,40, 41, 42 but again, correlation is not causation. Does sugar cause depression? Or do depressed people consume sugar to give themselves what little pleasure they can muster? There is no doubt that Cathy Guisewite’s eponymous cartoon character Cathy is both depressed and a chocoholic. But are these related, and which caused which? Is sugar consumption a contributor of the depressed state? Or is addiction a necessary intermediate step between sugar consumption and depression? The answer to all of these is a definite maybe.
Your Gut Feeling
But the more immediate question for all of us: Is your sugar consumption really under your control? Common wisdom says you are in control of every item you put in your mouth. And common sense would also suggest that is true (except we know from Part II that in addiction, you’re really not in control—the drugs are doing the talking via dopamine). What if something else is also talking, feeding your brain with devious and distracting thoughts—like your bacteria? You might think that your gut microbiome, consisting of 100 trillion bacteria representing several hundred species and residing inside your intestine, would not be immediately connected to your brain. Nonetheless, your gut microbiome appears to have a mind of its own, and it very well may control yours.43, 44
Every person on earth harbors his or her own individual Amazon rain forest, with unique creatures living on and in them. The bacterial species found within a person’s gut can identify him or her by a unique microbial signature.45 Yet the human gut microbiome is very clearly and rapidly responsive (within as little as two days) to dietary manipulation,46 and why not? Different nutrients will make their way farther down the intestine based on different aspects of the diet, such as what carbohydrates you are consuming, whether those carbohydrates are fermented, and whether they are accompanied by the corresponding fiber inherent in that food.47 Different bacteria like to grow in different dietary “soups” to different extents. In fact, changes in the microbiome have been associated with increased risk for obesity in both directions. For instance, transferring obesogenic bacteria from one mouse strain to another can cause the recipient mouse to become obese.48 This was anecdotally demonstrated in a human, where an unfortunate woman who received a fecal transplant to treat her infectious diarrhea became massively obese afterward.49
Conversely, ingestion of certain strains of probiotics (friendly bacteria) or prebiotics (dietary components such as fiber that let friendly bacteria grow) have been associated with weight loss50 and improvement in certain disease states.51 Other studies have found probiotics can influence mood and cognition.52 Microbial diversity may be protective against the various diseases of metabolic syndrome and obesity,53 and possibly depression. Your bacteria talk loud and clear, and apparently your brain listens. Remember, 90 percent of the serotonin made in your body is used by the gut for various purposes; serotonin happens to be pretty versatile.
Only 1 percent of your total body’s serotonin is in your brain, impacting, among other things, your level of well-being and contentment. Apparently a happy gut means a happy you. These bacteria may alter our emotional state and our dietary preferences through indirect communication with the emotion centers within our brain.
The one undeniable fact is that of all the items in the grocery store, sugar is the only one that is independently associated with depression and addiction and metabolic syndrome. And, as we’ve already noted, it’s undoubtedly the cheapest way to pleasure, and the surest path to unhappiness.
But fear not, there does appear to be one dietary item that can mitigate the damage that sugar does to the brain and promote the biochemistry and the processes that can predispose us to happiness. And perhaps not surprisingly its presence in the diet correlates positively with tryptophan and negatively with sugar. What is this magic chemical? It’s omega-3 fatty acids, of all things. A type of fat. Something we were told to avoid forty years ago. Another item that’s pretty hard to come by in the Western diet. Perhaps this is another reason that happiness has eluded so many of us.
Brain Food
Omega-3s come in two main flavors: eicosopentanoic acid (EPA) and docosohexaenoic acid (DHA). Everyone thinks these two omega-3s are found in fish. They are, but there are some qualifications to that statement. Fish don’t make omega-3s; fish eat omega-3s. Rather, omega-3s are made by green leafy plants either in the sea or on land. Algae are the best source of omega-3s around. The fish eat the algae. We eat the fish. So we purchase our omega-3s secondhand, and at a premium to boot. But wild fish eat algae. Farmed fish eat pellets. Sometimes the pellets are made from other fish, which, even if they ate algae, are now pretty diluted. Sometimes they are made from corn. Since farmed fish are fatter—see, it happens to them as well!—they have a slightly higher omega-3 content, but their omega-6 content (which drives inflammation) is extremely high; thus wild fish is a more expensive but smarter choice.54
The Hacking of the American Mind Page 12