15.2: Diet and the Brain

Although the brain is only about 2% of adult body weight, it uses about 20% of the oxygen and calories used for basal metabolism (Chap. 13). Neurons must constantly make neurotransmitters, pump ions (not “pump iron”!) to maintain polarized membranes (Figure 15.2), etc. The brain is extremely sensitive to lack of oxygen or fuel.

Brain damage can occur in drownings after only a few minutes from a lack of oxygen. An insulin overdose can cause blood-glucose to plummet, resulting in a coma from a lack of fuel. (Glucose is the only fuel the brain uses under ordinary circumstances.)

Many vitamins (e.g., niacin, thiamin, B6 , B12) and minerals (e.g., iron, zinc) play a critical role in making neurotransmitters and in the chemical reactions that supply the large amounts of ATP-energy needed by the brain.

Hampering neurotransmitter and/or ATP production means hampering brain function. As examples, a severe lack of niacin causes the mental impairment seen in pellagra, and a severe lack of thiamin causes the paralysis and mental confusion seen in beriberi (Chap. 1).

Excesses of these nutrients don’t enhance brain function. Large amounts taken as supplements can be toxic, e.g., liver damage and flushing of the face and hands with niacin; headache, irritability, insomnia, and weakness with thiamin; nerve damage with B₆; diarrhea with B₁₂.

The Developing Brain

During infancy, the brain continues to grow. So in addition to oxygen, glucose, vitamins, and minerals, the brain needs a lot of building blocks (the brain is rich in fat and protein). (As a reminder, the advice for a low-fat diet is not for children under age 2; Chap. 4.) The dry weight of the brain is about 80% fat, and is very rich in cholesterol. (A 3-oz serving of beef brain or pork brain has about 2000 mg cholesterol. Scrambled eggs and brain is—or at least used to be—a popular dish in the Midwest.)

When infants are malnourished, brain growth is a high priority (the head is relatively large on the emaciated body of an infant with severe protein-calorie malnutrition). Severe malnutrition while neurons are dividing (up until about 1 year of age) can permanently hamper brain growth, because beyond this crucial period, neurons stop dividing, and the child is permanently left with fewer neurons. For this reason, breast- feeding can be crucial for infants in places where severe malnutrition is common.

If a child is severely malnourished after the neurons have reached their full number, the neurons don’t grow fully in size. However, it appears that neurons can “catch up” in size once an adequate diet is available. It’s unclear if a child may be left with subtle effects like moderate learning and behavioral disabilities.

It’s hard to isolate the effects of malnutrition. Many factors (environmental stimuli, infectious diseases, etc.) affect learning and behavior. However, it appears that providing an enriched environment along with an adequate diet to children who have been severely malnourished can do much to normalize brain function.

Lead

A child’s brain continues to develop rapidly even after the brain has stopped growing. Nutritional deficiencies as well as various toxins affect the developing brain. Lead is particularly toxic. Many children in the U.S. have high blood levels of lead, indicating substantial exposure to its toxic effects. Lead is toxic to both children and adults, but children are especially vulnerable.

Lead is a potent poison with widespread effects. It can cause kidney damage (which can cause high blood pressure) and damage to red blood cells (which can cause anemia). It can also damage the nervous system (which can cause intellectual disability or nerve damage) and reproductive system (which can cause infertility).

The atomic structure of lead is similar to calcium, iron, and zinc—each has 2 electrons in its outer electron shell (Chap. 3). This is why lead can displace and disrupt the activities of calcium, iron, and zinc ions in the body. (Calcium, iron, and zinc are essential mineral nutrients; lead is not.)

Essential minerals often act as crucial accessories to enzymes; lead does much of its damage by interfering with the activities of many enzymes throughout the body. In the developing brain, this interference can have severe consequences.

Lead poisoning was much more common in the past. It has even been theorized that severe lead poisoning caused infertility and mental illness in the ruling class of ancient Rome, and that this was a factor in the fall of the Roman Empire. In ancient Rome, lead plumbing contaminated their drinking water, and lead utensils and vessels (used for cooking, drinking, and storage) contaminated their food and drink.

Lead ingestion now is relatively low, but the Environmental Protection Agency states that even low doses of lead are a serious threat to the nervous system of young children. In many studies, lead exposure in fetuses and young children has been linked to delay in mental and physical development.

One study with a particularly long follow-up suggests that effects of low-level lead exposure in early childhood persist into young adulthood. In 1975‑1978, all first and second graders from two predominantly White school districts in Massachusetts were asked to provide their lost baby teeth.* Based on the amount of lead in the teeth, 270 children (about 7 years old) were selected and divided into two groups—lower vs. higher lead exposure (no one had symptoms of lead toxicity). Children with the higher levels measured lower in intelligence, speech and language processing, and classroom performance.

In 1988, 132 of these children (at about age 18) were compared again. All of them now had very low blood-lead levels, but the young adults with higher early‑exposure (based on the amount of lead in their baby teeth) were more likely to have poorer grades and more absenteeism in high school, reading disabilities, lower test scores in grammatical reasoning and vocabulary, poorer hand- eye coordination, longer reaction times, slower finger-tapping speed, and were 7 times more likely to drop out of high school.

Although studies like this aren’t proof of cause-and-effect (their lead exposure might be related to other determining factors), animal studies support the relationship. Monkeys exposed to low levels of lead only during their first three months of life continue to show learning impairments as adults.

There’s still much debate about what blood lead level in pregnancy or childhood is damaging to a child’s nervous system. Government agencies use available data to set standards for lead exposure. The maximum allowable levels set by various agencies has steadily gone down as more studies show adverse effects of low doses.

Lead absorption: When the body is growing fast, lead is easily absorbed. Compared to adults, infants and young children absorb 5 to 10 times more lead from a given dose. Dietary deficiencies also have an effect. Lead absorption and/or toxicity is higher when iron, calcium, or zinc is also deficient. Unfortunately, these mineral deficiencies are quite common among young children and women of childbearing age.

Lead exposure: Several changes have greatly reduced our exposure to lead—less use of leaded gasoline, lead-containing house paint, lead-containing plumbing, lead-soldered cans for canned foods, and less lead released by industry. Blood-lead levels in U.S. children have shown a parallel decline. But much of the lead released earlier (from industrial pollutants and combustion of leaded gasoline) and dust from old leaded house paint still persist in the soil. Lead can be drawn into food grown in this soil.

Food isn’t a major source of lead exposure in this country. Our most significant source is drinking water coming through old lead water-mains and service pipes and household plumbing with old lead pipes or newer pipes soldered with lead.

Lead pipes are now banned in new plumbing for drinking water (although lead- containing faucets are still sold). Also, the amount of lead allowable in water is lower, and suppliers are required to notify customers of any lead in the water.

Homes older than 80 years might still have lead pipes, which should be replaced. Lead solder on pipes is less serious (although more widespread), especially if the solder is more than 5 years old (lead solder dissolves more easily during the first 5 years).

If your household plumbing is suspect, your local water or health department may offer advice and help. Also, the Environmental Protection Agency provides advice and information https://www.epa.gov/lead

In 2014, Flint, Michigan, had a crisis of lead contamination in drinking water when the water source was switched from Lake Huron to the Flint River as a cost-saving measure. Anti-corrosives weren’t added to the water flowing through old lead pipes.Thousands of children were exposed to toxic levels of lead in their drinking water.

In slum areas, old, peeling, lead-based paint is a major source of exposure. Again, young children are especially vulnerable, since they often eat paint flakes or put things in their mouth that are contaminated with paint dust in the house or yard. Similarly, one must be cautious in removing layers of old lead- based paint when renovating old homes, since lead can be absorbed by inhaling lead fumes or dust.

Canned food from lead- soldered cans can be contaminated with lead. But cans aren’t a major source, since about 95% of the cans used for canning foods in this country no longer have lead solder.

Food or drink kept in lead-glazed pottery (typically brightly colored and shiny) can be a source of lead. Lead can leach out if the pottery isn’t fired at a sufficiently high temperature. Oven-proof stoneware or porcelain is fired at high enough temperatures, as is most lead-glazed pottery made in the U.S.

Lead dissolves easily in acid. So lead contamination occurs more easily when acidic food and drink, such as orange juice, wine, coffee, spaghetti sauce, and vinegar, are put into improperly fired lead-glazed pottery. Drinking orange juice kept [in the refrigerator] in a lead-glazed pitcher has caused severe lead poisoning. Wine, brandy, etc., shouldn’t be stored in lead-crystal decanters, and food shouldn’t be stored in lead-crystal dishes. Lead foil on wine bottles is being phased out.

The ability of acids to dissolve minerals and metals such as lead is a general chemical principle. Cooking acid foods in cast-iron cookware increases the food’s iron content; acid made by bacteria on teeth dissolves calcium in teeth; vinegar softens a chicken bone by dissolving its minerals; acid is used to etch glass and metal; minerals dissolve in stomach acid, allowing us to absorb the minerals; soft water is slightly acidic and picks up more lead from lead pipes and lead solder.

^{*Lead tends to go where calcium goes, and calcium is most concentrated in bones and teeth. As mentioned in Chap. 14, taking calcium supplements of ground-up bone (bone meal) or dolomite (a natural rock rich in calcium) isn’t advised, since they might be contaminated with lead or other toxic elements.}

Food and Mood—The Tryptophan Connection

Can what we eat alter our mood? As tantalizing as this question is, the scientific tools and basic knowledge needed to explore it are only now emerging. However, what little we do know is intriguing.

The neurotransmitter serotonin has a calming effect and is made from tryptophan, one of the nine amino acids essential in our diet. Although most neurotransmitters are made from substances made easily in the body, the tryptophan needed to make serotonin must come from the diet.

Animals fed tryptophan-deficient diets make less brain serotonin and become irritable, hypersensitive to pain, and develop insomnia. (Alteration of serotonin activity also is a common effect of psychedelic drugs, e.g., LSD, which is structurally similar to serotonin.

Ecstasy—once popular among college students—is a hybrid of amphetamine and the hallucinogen mescaline that raises serotonin activity. It damages serotonin- producing neurons in rodents and primates; brain-imaging studies show a similar effect in humans.)

Since tryptophan comes from dietary protein, one might expect that a high-protein meal would raise brain tryptophan and serotonin levels. In fact, the opposite occurs, which takes a bit of explaining.

Tryptophan Transport into the Brain

The brain gets its tryptophan from blood, but tryptophan can’t enter the brain directly. It’s brought in by a special carrier that it shares with some other amino acids. The carrier doesn’t discriminate; it simply carries amino acids in, in proportion to their concentration in the blood. In other words, the amount of tryptophan that gets into the brain depends on the relative amounts of “competing” amino acids in the blood.

Imagine that the only way to get to an island (the brain) is by a boat (amino acid carrier) that holds 8. If the waiting crowd has 3 times more men (competing amino acids) than women (tryptophan), the boat picks them up in that proportion (6 competing amino acids and 2 tryptophan). But if there are equal numbers of men and women in the crowd, fewer men (4 competing amino acids) and more women (4 tryptophan) get in.

Protein has very little tryptophan compared to the competing amino acids. This means that although a high-protein meal puts more tryptophan into the blood, it puts in even more of the competing amino acids. As a result, less tryptophan gets into the brain, and less serotonin is made.

Effect of Insulin on Brain Tryptophan: So far, the only insulin effect discussed has been the effect of causing cells to take in glucose from the blood (Chap. 9). But insulin also causes cells to take in tryptophan’s competing amino acids from the blood, allowing more tryptophan to enter the brain.

A high-carbohydrate meal may change the odds in favor of tryptophan by causing a rise in insulin. The sequence of events would be: (1) more insulin, (2) fewer competing amino acids in the blood, (3) more transport of tryptophan into the brain, (4) more production of brain serotonin, and (5) a calming effect.

This sequence may make some people feel sleepy after a high-carbohydrate meal. A calming effect is also theorized to be a reason why people often find comfort (“tranquillity”) in carbohydrate-rich foods (e.g., candy).

Tryptophan Supplements

Because of the tryptophan/serotonin/calm and the tryptophan-deficiency/insomnia connections, tryptophan has been sold as a dietary supplement and promoted as nature’s sleeping pill, tranquilizer, etc. Big doses have been self-prescribed for a variety of ills, including insomnia, premenstrual problems, and arthritis. (In the Minneapolis-St. Paul metropolitan area alone, an estimated 7400 women took tryptophan in 1988.)

This practice was worrisome for several reasons. One was that the effects of large doses in such uncontrolled circumstances (i.e., people in various states of health taking tryptophan haphazardly) weren’t known. When a nutrient is taken in huge amounts, its action is that of a drug rather than a nutrient.

There’s no reason to expect that taking tryptophan would affect only brain serotonin. Tryptophan has other functions (e.g., it’s used to make protein and niacin), and serotonin is made and used in tissues other than the brain. Also, more tryptophan into the brain means less of the competing amino acids—amino acids which also have important functions in the brain.

We know that nutrients that are essential to the body in small amounts can have toxic effects in large amounts, e.g., liver damage from large doses of vitamin A or niacin, intellectual disability from a large accumulation of the essential amino acid phenylalanine in the disease phenylketonuria (PKU; Chap. 3). With very large doses of tryptophan, excessive production of serotonin might possibly occur under certain conditions. Chronic liver disease, for example, reduces the blood-level of many of tryptophan’s competing amino acids.

A high level of brain tryptophan and serotonin may play a role in the coma that can result from severe liver disease. One could say that a step beyond calm is sleep, and a step beyond sleep could be coma.

Another concern is that tryptophan is classified in this country as a dietary supplement rather than a drug. Supplements don’t need to pass the rigorous tests given to drugs (i.e., is it safe, effective, and pure?), and can be purchased freely without the package inserts (listing possible side effects, etc.) that accompany even nonprescription drugs.

Calls for classifying some dietary supplements as drugs are drowned out by loud protests by those who make and sell supplements and those who buy them—transactions worth billions of dollars.

In 1989, tryptophan supplements were linked to a mysterious epidemic of a serious, sometimes fatal, and normally rare disease characterized by severe muscle pain and an abnormal proliferation of certain white blood cells. About 5000 people were struck with this disease. More than 60% were left with severe symptoms, such as painful nerve and muscle damage, and there were at least 38 deaths.

The Food and Drug Administration recalled all tryptophan supplements. (The epidemic occurred almost exclusively in the U.S. In Canada, tryptophan is available only by prescription.)

It’s unlikely that the connection to tryptophan supplements would have been made, had there not been so many people taking them and had the adverse effect been more subtle, e.g., a vague symptom, such as fatigue, instead of a rare and severe disease. At the time, it wasn’t known whether the disease was a toxic effect of the large doses of tryptophan itself, a breakdown product of tryptophan, a contaminant, or a combination of these. It now appears that the toxicant was an inadvertent byproduct of the manufacturing process, and not tryptophan itself. But even without such contamination, a widespread and casual practice of taking tryptophan is still a matter for concern.*

^{*The same concern applies to supplements of melatonin, a hormone made by the pineal gland that increases sleepiness. It can help prevent jet lag, but it’s unclear what else it does. Claims that melatonin supplements reverse aging are unfounded.}

Nutrients and Brain Dysfunction

Because so little is known about how the brain works (what’s the brain chemistry of remembering your phone number?), newly proposed relationships between nutrients and brain function are largely speculative. This provides marketing opportunities for purveyors of dietary supplements (e.g., “smart drinks”).

There’s no question that nutrient deficiencies can interfere with brain function (e.g., the dementia of the niacin-deficiency disease pellagra), and it goes without saying that such deficiencies should be corrected.

The problem occurs when these connections are used to support claims that huge doses of certain nutrients can enhance brain function or cure a dysfunction. Depression can result from deficiencies of some B-vitamins, but if a person’s depression isn’t due to a vitamin deficiency, taking vitamins isn’t going to help—except perhaps for a placebo effect.

“Orthomolecular therapy” uses huge doses of vitamins to treat behavior disorders. A task force of the American Psychiatric Association has investigated this therapy and found it to be ineffective (aside from placebo effects).

Alzheimer’s Disease

Scientists have tried without much success to use nutrients to correct brain dysfunctions like Alzheimer’s, a disease of severe memory loss. The brain doesn’t make enough of the neurotransmitter acetylcholine, which plays a role in memory. Acetylcholine is made from acetate and choline, both of which are made by the body.

Large doses of lecithin† have been tried in patients, in hopes of “pushing” acetylcholine production and enhancing memory, but controlled studies haven’t found that it helps.** This is not surprising, since there’s a loss of acetylcholine-producing neurons in Alzheimer’s.

There are 2 kinds of Alzheimer’s: Early-Onset (onset age 30 to mid-60s) and Late-Onset (mid-60s and older). Genes that cause each kind haven’t been identified, but genes that affect risk have been found (“risk genes”).

For example, there are several forms of a gene that makes a protein called apolipoprotein E. One form is linked to a higher risk of late-onset Alzheimer’s, another linked to lower risk, and yet another form doesn’t seem to increase or lower risk.

People can get tested to see which form they have, but many people prefer not to know. Just because you have the higher-risk form of the gene doesn’t mean you will get late-onset Alzheimers, nor will having the lower-risk form mean that you won’t get it. Also, as yet, there are no effective drugs for prevention, and only mildly effective drugs for treatment.

The identification of a defective gene that can cause Alzheimer’s (even if it isn’t the only cause) would be a breakthrough. From such a discovery, the protein it makes can be identified, providing a key to understanding the cause of the disease. Once the cause is understood, effective treatments and preventative strategies can be devised.

^{†Lecithin is the choline-containing fat found in food and in our cell membranes (Chap. 5). Choline itself tastes bitter and imparts a “fishy” body odor when taken in big doses. Acetylcholine isn’t given, since it would break apart in digestion; even if it were injected into the blood, it can’t get into the brain. The brain makes its own acetylcholine.
**Lecithin has been found to be helpful in treating some patients with another disease—tardive dyskinesia, a neuromuscular disorder caused by long-term use of certain antipsychotic drugs.}

Diet and Behavior

Despite claims to the contrary, diet as a cause of such behaviors as criminality and hyperactivity isn’t supported in double-blind studies. Likewise, double- blind studies haven’t found criminal, delinquent, or hyperactive behavior to be helped by “megavitamin therapy” or dietary manipulations such as eliminating sugar. Double-blind studies are essential, since evaluations of behavior are subjective and prone to bias.

Also, dietary changes may improve behavior without the diet itself being directly responsible. Many parents found the Feingold diet (an elimination diet popularized as an effective treatment for hyperactivity in the 1970s by pediatrician Benjamin Feingold) helpful in treating their hyperactive children.

But when the substances (a wide variety ranging from certain artificial colorings to substances found naturally in common fruits) were tested in a double-blind fashion, there were no differences in behavior between the experimental and control groups. (In an occasional hyperactive child, behavior seemed to be affected by dietary substances; if this is substantiated, of course the substance should be avoided.)

Highly restrictive diets change the entire family dynamics. This change is what’s thought to be the main reason for the improved behavior. A lot more time is spent shopping for foods, meals are changed and more time is spent preparing them. Children get more positive attention, and behaviors like hyperactivity are blamed on the food rather than on the children themselves.

Sugar is popularly believed to cause hyperactivity in children (and delinquent activity in adolescents). But controlled studies in children and adolescents suggest the reverse—that sugar has a calming effect. This finding is in line with the sugar-serotonin connection mentioned earlier.