At least 85 percent of all Americans have major nutrient deficiencies that adversely impact their health in a variety of ways, including accelerated cognitive decline. This seems shocking in a country where nutritious food is plentiful, but the problem is SAD—the Standard American Diet—that most men, women, and children are consuming.
Everyone needs a personalized plan to meet their key nutrient needs, and ideally they would do it with food. But in reality, and certainly after seeing thousands of patients over thirty years as a physician, I have yet to meet a person who eats well all the time. Furthermore, nutrient content in food has decreased substantially over the last several decades, as processed food has crowded out real food. Even whole foods—fruits, vegetables, and whole grains—have been diminished nutritionally through industrialized farming, the use of pesticides, and other practices, compounded by the amount of processing done by big food manufacturers. Considering all the toxins in our environment today, we need extra nutrients, certainly not fewer, to detoxify and remove these chemicals from our tissues.
Adding vitamins, minerals, and other valuable nutrient therapies can only enhance a healthy eating plan—they can’t replace it. Supplements will never make up for eating junk food, skipping a workout, being stressed out, or getting poisoned by toxins like pesticides or hydrogenated fats. Eating well—especially choosing brain-boosting foods and reducing your sugar load—should be a priority if you want to correct any deficiencies.
It’s important to note the limitations of looking at the effect of one nutrient or a single compound at a time on cognition; that isn’t how Mother Nature works. Typically, dozens or hundreds of nutrients and compounds interact to enhance physiological function. One agent on its own often will not work as well as several compounds used together.
That is why many supplement compounds sold with claims to support brain function use anywhere from five to twenty ingredients at the same time, though most studies evaluate these compounds one at a time. (The reality is that those combinations are rarely, if ever, tested together.) Their manufacturers can’t claim that a multi-ingredient compound will prevent memory loss or improve cognitive function, because such a claim would have to be substantiated with research, in complex and sophisticated studies that would cost millions of dollars. Instead, manufacturers typically rely upon a vague statement that doesn’t require research, like “this product supports healthy brain function.” (For an example of a product that has crossed the line in terms of claims and research, see the box “The Problem with Prevagen” on this page.)
With this limitation in mind, here are key nutrients—not compounds with a multitude of agents—that we know, without a doubt, are essential for preventing memory loss.
These nutrients are necessary for optimal cognitive function, and strong evidence supports their use. Some of these nutrients can be found in food, but if that isn’t realistic (because of the amount of that food you’d have to eat in a day), there are supplement options as well.
• Vitamin D
• Vitamin B12
• Mixed folates (also known as vitamin B9)
• Chromium
• Long-chain omega-3 fats (fish oil)
• Probiotic source
• Magnesium
Vitamin D is a fat-soluble vitamin, but once it has been converted to its active form, it functions like a hormone. Nearly every cell in your body has a vitamin D receptor, and vitamin D modifies how your cells function.
For the last 100,000 years, humans have obtained vitamin D from sunlight. (The sun stimulates vitamin D production when a form of ultraviolet light reacts with a cholesterol molecule in the blood.) Early humans, their skin exposed with limited clothing, spent twelve to sixteen hours daily hunting and gathering in direct sunlight.
Today, of course, most people wear clothing and are indoors most of the time. And for six months of the year (late fall–winter and early spring), people living north of Santa Barbara, Dallas, and Atlanta don’t make any significant vitamin D. And when we are in the sun, wearing sunscreen, which is essential for guarding against skin cancer, blocks the skin from making vitamin D.
While a twenty-year-old should be able to make enough vitamin D from twenty minutes of sun exposure, he or she would have to be on a beach or by a pool in a skimpy bathing suit (lots of skin showing and no sunscreen, for maximum sun absorption) between ten a.m. and two p.m. with peak sun. In contrast, the skin of someone fifty or older isn’t nearly as efficient at using sunlight to convert cholesterol into vitamin D. That person may require sixty minutes to make the same amount of D, with similar attire and time of day. Spending an hour in the midday sun—without sunscreen—is a tall order for most of us. Even living in Florida, the Sunshine State, 90 percent of my patients are vitamin D deficient unless they take a supplement, and the majority of them need to take at least 2,000 IU daily to achieve an optimal level, above 40 ng/mL (nanograms per milliliter, as measured in the blood).
Experts argue about what constitutes a normal vitamin D level, but most would agree that a level less than 30 ng/mL is deficient; that greater than 30 is acceptable; and that 40–70 is optimal. More than 100 ng/mL is associated with significant (negative) side effects. Vitamin D supplementation is extremely safe, and dosing up to 3,000 IU daily has never been associated with any side effects or toxicity.
Without vitamin D supplements, most Americans become deficient and show bone loss and elevated risk for fracture, heart disease, diabetes, and weight gain. Randomized clinical studies have shown that giving vitamin D decreases the risk for cancer by up to 40 percent and also reduces the risk for autoimmune diseases. It also plays a major role in brain health.
Vitamin D crosses the blood-brain barrier, the protective cellular barrier that lets certain nutrients into the brain and keeps other substances out. Once vitamin D passes through, it diffuses easily into the cerebrospinal fluid. Several studies have shown that low vitamin D levels are associated with a higher risk for cognitive decline and dementia. Vitamin D deficiency increases your risk for multiple sclerosis as well. People with higher vitamin D levels appear to have larger brains than people with low vitamin D levels. The active form of vitamin D, called 1,25-dihydroxyvitamin D, stimulates brain cell growth, including in the hippocampus—the memory center—and activates numerous neurotransmitters in the brain.
Studies using vitamin D to slow existing cognitive decline are still needed. In a small pilot study in India with eighty subjects, randomized to receive either a placebo or a vitamin D supplement, those who received the vitamin D showed greater improvements in cognitive function based on their performance on the Mini-Mental State Examination (MMSE). More research is needed.
At some point, after you have been taking vitamin D consistently for at least three months, you should have your blood levels of vitamin D checked. A measurement of 25-OH would indicate that this dosage gives you a normal blood level of vitamin D. Some people may have poor absorption and require higher dosing, although 2,000 IU daily will be adequate for most adults. Gluten sensitivity can limit nutrient absorption. If you take a vegetarian form of vitamin D (such as vitamin D2), it is extra important to check your level, as most of us absorb vitamin D2 differently.
Before we discuss the Better Brain nutrients, such as B12, folates, and chromium, that are generally found in multivitamins, it’s important to note a few facts about multivitamins, including how to locate quality supplements.
Most multivitamin supplements on the shelves of chain drugstores are low in quality and won’t deliver the potent levels of nutrients your brain and body need. Consumer advocate groups, such as ConsumerLab.com, which monitors the supplement industry, regularly conduct independent testing and point out that what is printed on the label isn’t necessarily what is in the bottle. (A rock-bottom price, for starters, should always give you pause, especially if you’re buying online and can’t examine the packaging for ingredients and expiration dates. Good supplements are not inexpensive.)
For one thing, it’s impossible to get all the vitamins you need in one small pill—all these nutrients cannot be combined and compressed to fit into a compact pill, due to their molecular structure. A quality multivitamin is most likely to be at least two pills, not one. My clinic offers four brands that I trust for quality: Designs for Health, Thorne Research, Metagenics, and ProThera. You can purchase their products online or through a health-care provider, including a licensed nutritionist or a physician.
If you want the best quality, here is a look at what should be in a multivitamin and what should not.
• Folacin or 5-MTHF (mixed folates)—not only folic acid
• Mixed carotenoids—not solely beta-carotene
• Mixed tocopherols—not only alpha tocopherol (manufacturers are required to label alpha tocopherol content by itself, but it should contain mixed tocopherols as well)
• Protein-bound minerals (malates, glycinates)—not oxides (like magnesium oxide)
• Zinc-to-copper ratio of 20 or more
• Organic copper (copper glycinate)—not inorganic copper (copper sulfate or copper carbonate), which is potentially toxic; see Chapter 8.
Vitamin B12 is an essential nutrient used by cells to convert glucose into energy. Brain cells are particularly sensitive to an inadequate B12 supply. When vitamin B12 levels decrease to dangerously low levels, brain cells die. You can have permanent, irreversible nerve damage and develop dementia from vitamin B12 deficiency, which, alarmingly, is becoming common.
For the last 100,000 years, we consumed some of our vitamin B12 from eating animal protein, but a surprising, indirect source was also crucial—dirt! When we eat dirt, we consume bacteria, and these dirt-laden bacteria ultimately produce vitamin B12. Our ancestors ate dirty plant foods, including roots and leaves, and dirty meat. Even up until the last century, dirt was still making its way into our food supply, providing a guaranteed source of vitamin B12. Today our foods are washed, sometimes irradiated, and coated in plastic. There isn’t much dirt left, and gone too are the helpful bacteria that triggered the production of a vital nutrient.
Certain groups of people are at high risk for vitamin B12 deficiency. First are vegetarians and vegans (not because they are eating dirt-free plant foods, but because they do not consume animal protein). If you are following a healthy vegetarian or vegan eating plan, you’re likely well aware of this concern, and you know the remedy is simple: take a vitamin B12 supplement (50–1,000 mcg daily depending upon your health issues).
The much larger group at risk for B12 deficiency are people who lack stomach acid, as stomach acid is essential to absorb nutrients, especially vitamin B12. As we age normally, we lose stomach acid—and with it the ability to absorb vitamin B12. Sometimes this condition is mild, but it can be severe. Though there are symptoms (see list on this page), the only way to know for sure is to have your vitamin B12 levels measured through bloodwork.
Over-the-counter and prescription heartburn medications, however, are a bigger issue than acid reductions caused by normal aging. Millions of people now take heartburn medications that decrease the absorption of vitamin B12 as well as other nutrients such as calcium. Acid-blocking medications negatively impact the microbiome. (Many such medications now carry a “black box” warning to signal their stomach acid–and nutrient-blocking side effects.) The most powerful acid blockers are the proton pump inhibitors, including Nexium, Prilosec, Omeprazole, Lansoprazole, Protonix, Aciphex, Dexilent, and Prevacid. These medications are effective treatments for those with serious gastric reflux issues, but they can also cause extensive nutrient deficiencies. If you are using these types of acid blockers, a high-quality supplement regimen is therefore very important. Other antacids that block nutrient absorption include Ranitidine, Zantac, Tagamet, Cimetidine, Tums, Rolaids, and Mylanta. If you use any of them regularly, be sure to check for the signs listed below.
Here are symptoms and signs suggesting vitamin B12 deficiency:
• Tingling, numbness, and burning in your extremities (neuropathy)
• Memory problems
• Poor balance, especially standing with your eyes closed (ataxia)
• Anemia
• Elevated MCV (mean corpuscular volume) on a complete blood count (CBC) lab test
Don’t miss these signs, as over time they can cause permanent neurological injury.
Testing for vitamin B12 deficiency is simple, although your doctor will need to order it as a blood test, and low-to-normal levels may require additional testing. Most labs consider a B12 level below 250–300 pg/mL (picogram/milliliter) to be low, and low-to-normal to be 300–500 pg/mL. Above 500 pg/mL is desirable.
If you have borderline low levels, and also the signs or symptoms noted above, then additional testing may be warranted. On occasion, a blood level could be above 250–300 pg/mL in the low-to-normal 300–500 pg/mL range, but such a result might not reflect the fact that intracellular levels are actually low. The result could be permanent neurological damage. A test to clarify borderline low B12 levels assesses vitamin B12 function, namely a methylmalonic acid level. Vitamin B12 should lower methylmalonic acid, so if this level is high, that is a functional sign of B12 deficiency.
In the past, we treated people with vitamin B12 shots and intravenous treatments, but fortunately those are not needed with the updated dosing that many physicians and other health-care practitioners now follow. The current recommended daily allowance (RDA) for vitamin B12, however, does create some confusion: it varies from 2 to 3 mcg daily, which is enough to meet the needs of a teenager without any intestinal problems but insufficient for many others. Many multivitamins provide 10 mcg of B12 to meet this RDA need, but for adults with stomach irritation and limited stomach acid production, including that caused by normal aging, this will leave too many of them vitamin B12 deficient.
That’s why I typically recommend a daily multivitamin with at least 100 mcg, and the multivitamins I carry typically have 500 mcg of vitamin B12 to ensure it meets the needs of 99 percent of my patients. (Rarely, I’ll meet a patient with gastrointestinal issues who requires 1,000–2,000 mcg daily.) Back when we were limiting our therapy to 10 mcg daily, B12 shots were pretty common, but now that we have dosing at the 1,000–2,000 mcg levels, that just seems like added expense and bother. Sublingual levels are also available with lower dosages, but they cost more than regular oral pills with 1,000–2,000 mcg dosing.
A variety of studies have tried treating adults with vitamin B12 to help prevent cognitive decline and improve cognitive performance. Thus far these studies have been pretty disappointing. Therapies with B12 have not slowed cognitive decline. They will work only for those who are vitamin B12 deficient. However, allowing yourself to become deficient in B12 will likely harm your brain. You can avoid deficiency with a good-quality multivitamin supplement.
I recommend that you take a multivitamin with at least 100 mcg of vitamin B12 daily. If you have any of the symptoms noted on this page, have your vitamin B12 level checked. If you use medications to treat heartburn or dyspepsia, you may need at least 500 mcg of vitamin B12 daily. In my clinic, I offer a multivitamin with 500 mcg of vitamin B12. Some people absorb vitamin B12 very poorly and need up to 2,000 mcg daily.
High intakes of vitamin B12 are not harmful, unless an individual has a deficiency in folate, a related nutrient. Because it is harder to diagnose folate deficiency when someone is taking extra vitamin B12, let’s talk about folate deficiency next.
Folates, which are a group of B9 vitamins, are required for methylation, a process that repairs cellular DNA and removes toxins. People with folate deficiency are at elevated risk for depression, heart disease, cognitive decline, and dementia. Rich food sources of naturally occurring folates include leafy green vegetables, beans, and whole grains.
Most people can convert folic acid, the synthetic version of folate found in supplements, into active folates. (Folic acid is also added to foods such as flour and cereal.) Two examples of active folates that play a big role in brain health include folacin and methylenetetrahydrofolate (a tongue-twister of a name abbreviated as 5-MTHF). However, up to 40 percent of people are not able to effectively convert folic acid to these active forms, and most inexpensive supplements rely upon the assumption that you can do so. If you’re in that group, then the five-dollar bottle of “folic acid” you bought at your drugstore isn’t doing you much good; nor are those fortified foods.
Folate deficiency, like vitamin B12 deficiency, is associated with a metabolic problem: high levels of the toxic compound homocysteine. High homocysteine levels are strongly associated with increased risk for dementia, depression, and heart disease. Yet short-term studies tracking people with high homocysteine levels found that treatment with high dosages of folic acid and vitamin B12 did not prevent cognitive decline. The role of homocysteine remains a complicated topic, hotly disputed in the nutrition science community, but most likely homocysteine is a sign of a metabolic problem, not the true cause of the injury—in this case, dementia, depression, and heart disease.
We do know that both folate deficiency and vitamin B12 deficiency can result in cognitive decline and dementia, as well as depression. Treatment with adequate dosing will help to prevent this. However, unlike vitamin B12, where excess dosages seem harmless, excess dosages with active folate can cause problems. Because folates help DNA repair itself (methylation), extra folates seem to repair cancer DNA as well, increasing the risk for colon cancer and colon polyp growth. Therefore, you don’t want to take more folate than you need.
Most people need at least 400 mcg of active folates, such as folacin and methylenetetrahydrofolate (5-MTHF), to prevent a deficiency state. But taking more than 1,000 mcg daily can lead to problems. People who eat plenty of beans, leafy green veggies, and whole grains can easily get 400 mcg of active folates daily. Adding at least 400 mcg of active folates in a daily multivitamin, and enjoying the healthy foods noted, will give you enough, but not too much, active folate, with a total supplement-plus-food dosage of 400–800 mcg daily. In some unusual situations, your doctor may recommend higher dosing, but this is a discussion I’ll leave to you and your personal physician.
A multivitamin with cheap, inferior ingredients, such as only folic acid, puts up to 40 percent of the population at risk for folate deficiency. That is why your multivitamin should specify mixed folates, including folacin and 5-MTHF. Genetic testing related to this issue is discussed in Chapter 2.
Chromium is a mineral that is essential for insulin sensitivity. I don’t know of any studies that show an association between chromium and cognitive decline, yet people with low chromium levels are more likely to be insulin resistant, and insulin resistance is the most important reversible cause of dementia. Giving a chromium supplement in randomized trials has not improved blood sugar levels, as studies didn’t target people with a chromium deficiency. However, in people with documented chromium deficiency, the supplement does improve blood sugar control.
Foods rich in chromium include meats, whole-grain products, high-bran cereals, green beans, broccoli, nuts, and egg yolks. Eating simple sugars increases chromium excretion—another reason to avoid added sugar. Ironically, people with diabetes are more likely to suffer from chromium deficiency, as chromium is lost with excess urination, worsening their already compromised blood sugar control.
The solution is really simple. Ensure you take a good-quality multivitamin with at least 400–800 mcg of chromium daily.
You can get adequate vitamin B12, folate, and chromium from a good-quality multivitamin. (See this page for recommended quantities.)
Next, let’s focus on what you won’t find in a multivitamin (besides adequate vitamin D): long-chain omega-3s, a probiotic source, and magnesium.
You read about the benefits of adding omega-3-rich seafood to your diet in Chapter 3. As a reminder, to reap the brain benefits of cold-water fish (such as wild salmon, sardines, or herring), I recommend you eat them at least two or three times every week. The least expensive way to get your long-chain omega-3 fats would be from eating wild canned salmon.
Yet at least 30 percent of my patients don’t like those varieties of fish, and for them it isn’t realistic for me to recommend it so frequently. I know from experience, as a physician and as someone who loves to cook and feed others, that if I ask an adult to eat something he or she truly dislikes, even if it’s beneficial, chances are they will not stick with it for the long term, unless their palates change. For those who do not care for the taste of cold-water fish, therefore, a supplement is a good alternative. Still (one more plug for one of my favorite foods), the benefits of eating fish are well established and far less controversial than taking fish oil supplements.
If you take long-chain omega-3 supplements, there are a few major concerns you should know about. The first involves dosing. Some companies sell fish oil products that contain inadequate ratios of beneficial DHA and EPA components and diluted omega-3 components. The result is a less effective, watered-down supplement.
A number of manufacturers have developed modified ratios, with extra EPA, but most of them guessed wrong when they made these modifications. Recent research has shown that DHA appears to be more effective than EPA. DHA is better at improving lipid profiles, decreasing inflammation, and improving cognitive scores than EPA.
In 1,000 mg of most natural sources of fish oil, there are about 500 mg EPA, 400 mg DHA, and 100 mg of other mixed omega-3 fats. However, some forms are modified to have 70 to 80 percent EPA and only 10 to 20 percent DHA; I’d suggest avoiding those EPA-enriched formulas. Pure DHA would be excellent, but it is very hard to find and quite expensive, so considering the cost and value, a fish oil containing 600 mg EPA and 400 mg DHA is acceptable—just not less DHA to EPA than that ratio. Furthermore, whatever long-chain omega-3 supplement you choose should have at least 1,000 mg (combined) of DHA and EPA. You might find a 1,000 mg capsule of fish oil, but read the label. It could have 300 mg of EPA and 200 of DHA, and 500 mg of other mixed omega-3s. That is only a 500 mg dosage of EPA and DHA.
The second concern is contamination. Most fish oil sold in the United States would not be permitted to be sold in Europe because it is rancid. It has been cheaply extracted and/or improperly stored, and its molecular components have broken down. It tastes awful. Good-quality fish oil should not have a bad fish oil flavor. Rather, it should taste like fresh wild salmon, which is fishy but pleasantly so—not “yuck” fishy. (Unless you have no sense of smell, you’re unlikely to miss the rank odor of bad fish. That’s what you need to steer clear of.) The simplest way to test your fish oil is to taste it. When fish oil comes as a liquid in a glass bottle, that’s easy, but when it comes in capsules, here is a tip—select one capsule from the bottle and stick a needle or pin into it, squeeze gently, and taste a drop. It should taste pleasant or return it.
High-quality fish oil with low levels of rancidity undergoes strict processing procedures, not something you’ll find in most inexpensive fish oils. I’m not just trying to spare you the experience of getting a whiff of something rotten. Consuming rancid fish oil is quite bad for you because you are ingesting a big load of oxidized free radical fats that damage your cell membranes, including those in your brain. Find high-quality fish oil or skip it altogether.
A third concern surrounding the benefits from fish oil involves the ApoE4 genotype. In studies, if researchers don’t control for the ApoE4 genotype (that is, identify and exclude it from trials), and everyone is given only 500 mg of EPA and DHA, then the entire group may not show any benefit. The results will be skewed if studies don’t control for ApoE4. We know that people with the ApoE4 gene need bigger dosages to benefit, but they also benefit more than people without the ApoE4 gene. I recommend that people with the ApoE4 gene get 2,000 mg of EPA and DHA daily.
Ensure you are eating fatty cold-water fish two to three times per week (wild salmon, sardines, herring, sole), or multiple servings of seaweed weekly, or take 1,000 mg of EPA and DHA in a high-quality fish oil supplement.
Vegetarians can aim for 500 mg of DHA from a seaweed supplement daily. (Seaweed has DHA, not EPA.) Vegetarians probably don’t need 1,000 mg. Animal protein consumption modestly raises inflammation levels. Vegetarians who eat well most likely have less inflammation than meat eaters, so 500 mg of DHA is likely sufficient.
The majority of people with an ApoE4 genotype should aim to consume 2,000 mg of EPA and DHA daily; check with your physician to confirm that this won’t conflict with other medications you might be taking.
In the last few years, there has been an intense interest in the connection between the gut microbiome and the brain. Increasing the diversity of gut microbes is clearly associated with reducing the risk for many neurological conditions, including dementia. As part of Step 1 in the Better Brain food plan, you should be eating a variety of probiotic-rich fermented foods daily to increase the diversity and quantity of good microbes in your intestinal tract, such as sauerkraut, kimchi, miso, natto, plain unsweetened yogurt, and kefir. Also, to keep those healthy microbes well fed and alive, eat at least ten servings (30 grams) of fiber from vegetables, fruits, beans, and nuts daily. (See Chapter 3 for more on fermented foods.)
A depleted gut microbiome increases your risk for cognitive decline, depression, and dementia. In Chapter 3, I explained how chemical sweeteners can wipe out good bacteria, but antibiotic use perhaps does the greatest damage to the gut microbiome. You don’t have much choice about taking an antibiotic if you have a severe infection (like meningitis or pneumonia), but you can safely cut your use of unnecessary antibiotics, such as those taken for a run-of-the-mill upper respiratory infection (the common cold). It will normally resolve with a bit of patience and time. If my own patients require antibiotics for infection, I recommend they add at least a two-month course of a probiotic supplement, and you should do the same.
If for years you have been consuming a cup of probiotic fermented foods and ten servings of fiber (30+ grams) daily, then I wouldn’t fret over taking a probiotic supplement—you probably don’t need one. But if you don’t meet those criteria, add a supplement. Over the long term, I recommend that you consume at least 5 billion microbes daily, year round (along with adequate fiber); I typically suggest starting with at least 25 to 50 billion microbes daily for the first few months. If you’ve never purchased a probiotic supplement before, you may be thinking those “billions” sound extreme, but they aren’t, when you consider that on average, a healthy gut is home to about 100 trillion microorganisms! Supplements with a variety of probiotic organisms are preferred, and better than one that provides only a few different microbes.
We know that magnesium improves blood sugar and blood pressure control, and that it is a strong predictor of shrinking—and not growing—arterial plaque. When I studied more than one hundred of my patients who shrank their arterial plaque load by at least 10 percent, I found that increasing magnesium intake was one of the most powerful predictors of improvement. And since arterial plaque growth, blood sugar, and blood pressure are all strong predictors of accelerated cognitive decline, I want to make sure you get your magnesium every day. Magnesium also helps reduce constipation, anxiety, migraine headaches, muscle cramps, and insomnia.
A challenge with magnesium supplements is quality. Inexpensive forms of magnesium come as salts, such as magnesium oxide, and can cause stomach upset and intestinal distress. Magnesium citrate is a bit better tolerated and is frequently chosen for its laxative activity. The best-tolerated form of magnesium with the highest absorption comes with protein-bound magnesium, such as magnesium glycinate and magnesium malate—magnesium chelated with protein. If taken in excess, all forms of magnesium can cause diarrhea.
Magnesium is also related to neuronal synaptic function. Synapses are the junctions between nerves, and neurotransmitters provide the biochemical connection between the synapses, impacting processing speed and function.
Magnesium appears essential for proper messaging to occur between brain cells. A recent small study with forty-four subjects randomized older adults with mild cognitive impairment to receive magnesium L-threonate or a placebo for twelve weeks. Multiple measures of cognitive function were obtained before and at the end of the study. In this small, short-term study, giving more than 1,000 mg of magnesium L-threonate daily improved cognitive ability and reduced cognitive impairment nearly to normal. The magnesium was divided into two dosages daily, likely to limit gastrointestinal side effects, which were equal in the two groups.
Good food sources of magnesium are seeds, nuts, beans, green leafy veggies, halibut, and bran, but 70 percent of people nationwide are deficient in this essential mineral, and in my clinic at least 50 percent won’t get the minimum RDA recommendation of 400 mg from food alone. Most people need to eat the foods noted above, and also take a magnesium capsule with 150–200 mg at bedtime to help meet this critical need.
For people with mild cognitive impairment, speak with your physician about daily dosages of 2,000 mg of Magtein Magnesium L-threonate, including 144 mg of elemental magnesium, keeping in mind that some sources of magnesium penetrate from the blood into the brain more effectively than others. Magnesium L-threonate is the form used in the study of forty-four subjects noted above and has been shown to increase brain magnesium levels nicely.
Ensure that you get at least 400 mg of magnesium daily from food and supplement sources. For people with mild cognitive impairment, talk to your doctor about using higher dosages of magnesium L-threonate therapy.
MAGNESIUM CONTENT IN FOOD
At a minimum, make sure to meet your key nutrient needs for a better brain on a daily basis: Vitamin D, a good-quality multivitamin with adequate vitamin B12 and folates (vitamin B9), and chromium, plus long-chain omega-3 fats, probiotics, and magnesium. From there, it’s not hard to make the jump to Step 2: adding other compounds to protect your brain from cognitive decline.
Peggy’s Better Brain Story: Vitamin Power
Peggy was a careful eater. At age sixty-nine, she’d been a vegetarian for years, and local organic produce was a staple of her diet. She had once grown much of it herself in her backyard garden, but after she was widowed, she moved out of her house and into an apartment. She had recently been having burning in her feet and was growing forgetful. Her son, my regular patient, asked if I’d evaluate Peggy, after she set her kitchen on fire when she forgot about a pan on the stove.
Though she ate well, when I asked her about supplements, she said she didn’t trust supplement companies and didn’t bother with them. As it turns out, she was low in two key nutrients that have a major impact on memory and cognitive performance—vitamin B12 and DHA.
On examination, I noticed that she could not feel any vibration with a tuning fork. She could feel light touch, but her vibration sense was gone, clearly a sign of nerve damage—as was the burning in her feet. Her cognitive testing showed adequate processing speed, but her verbal and shape memory were both really poor, putting her below the tenth percentile for memory scores. From her diet, exam findings, and cognitive score, I could guess her lab results before they returned—sure enough, low B12 levels (less than 100 pg/mL, in contrast to a more desirable level of 500 pg/mL and above); and very low DHA levels.
I suspect that when Peggy gave up her garden, and her own organic-soil-raised vegetables, she lost an essential if unexpected nutrient—dirt as a source of bacteria that made vitamin B12. On top of that, she wasn’t getting any long-chain omega-3s to support her brain. Now that she was buying her produce at the store, superwashed, sanitized, and packed in plastic, she wasn’t getting the vitamin B12 she needed.
Once she saw her own results, and I assured her that some supplement companies could be trusted, I loaded her with 2,000 mcg daily of vitamin B12 for one month, then dropped the ongoing dosage to 500 mcg daily, plus 500 mg of vegetarian DHA from seaweed every day. By two months, the burning in her feet was completely resolved, and when we repeated her cognitive function, it had returned to normal. Prolonged vitamin B12 deficiency can cause permanent, irreversible memory loss and neuropathy. I had met Peggy just in time.
A handful of compounds come with compelling research and tremendous potential to prevent cognitive decline, but they are still being studied, and there isn’t solid confirmation that they will work for everyone. And as their production is still fairly limited, they are also relatively expensive, especially when compared to sure bets like vitamins D and B12. However, especially if you have early cognitive decline, I would encourage you to discuss these supplements with your doctor and consider starting them now. If you have early memory loss, you may not want to wait for years while we keep studying them.
I’m putting curcumin at the top of the list of supplements to consider adding to your list of essentials in Step 1. That’s in part because of its potential brain benefits but also because it has many other beneficial properties: decreasing inflammation, fighting oxidative stress, and helping symptoms of arthritis. It is also being studied for helping to prevent and treat cancer. Those are beneficial side effects I’d like to see with other treatments, too!
You can get curcumin from certain foods, as it is derived from the turmeric root—the yellow spice commonly blended with Indian curry dishes. Cultures that ingest large quantities of turmeric have some of the lowest rates of dementia and memory loss in the world. However, the challenge is the actual amount you would need to consume, as curcumin is poorly absorbed from the gastrointestinal tract into the bloodstream. You would likely need to eat at least three heaping tablespoons of turmeric spice daily to reach the same levels that can be achieved with a single 500-mg high-quality curcumin capsule. (By high-quality, I mean a form that has been studied to be well absorbed and is not contaminated with heavy metals, which are commonly found in turmeric from India.)
Because my parents had arthritis, and I have noted early signs myself, I concluded I should be taking this compound, too. Optimistically, since I like curry-flavored foods, one morning I spooned a heaping tablespoon into a half cup of plain yogurt and stirred, thinking, I could easily get three tablespoons daily. I took a brief taste—and was I ever disappointed by that experiment! It was awful! I was immediately motivated to find another way to get curcumin, and I set out to find the best absorbed form of clean curcumin in capsule form for myself and my patients. (See Appendix 2 for details.)
Beyond its anti-inflammatory, arthritis-relieving, antioxidant, and cancer-fighting properties, curcumin has been studied for its effects on cognitive decline. The challenge is that original forms were poorly absorbed, while larger doses (which might be the most effective for addressing cognitive decline) have caused significant gastrointestinal symptoms. Recently, improved curcumin formulations have been introduced, with much better rates of absorption and gastrointestinal tolerability. One study that used these newer forms of curcumin has shown improved cognitive function.
Dr. Katherine Cox and her Australian research team evaluated 60 healthy adults (without memory loss), age sixty to eighty-five. Subjects were randomized to receive 400 mg of a well-absorbed curcumin formulation and a placebo, and sophisticated measures were used to assess their cognitive function pre- and post-therapy. Even after only three hours, researchers noted improved cognitive function with curcumin, but none in the control group. After four weeks, those receiving curcumin showed better cognition, plus subjects reported more energy and less anxiety.
Additional studies in humans have shown that giving curcumin decreased blood levels of beta-amyloid (the brain protein associated with Alzheimer’s disease); and in mice, giving curcumin enhanced hippocampal neurogenesis (regeneration of brain cells), helping to increase the size of the brain’s memory center.
It’s tempting to get excited by the potential of curcumin, but at least a couple of trials using less well-absorbed forms at higher dosages showed no benefit. One study showed no memory benefit to taking curcumin over forty-eight weeks, though this study did have some limitations. It was a small pilot study with only thirty-six subjects, and 21 percent of the curcumin treatment group dropped out due to gastrointestinal side effects. The dropout rate might have been related to the form of curcumin used, which had limited absorption. Another problem with the study was that researchers relied upon the Mini-Mental State Examination to assess for a change in cognition, which clearly might miss modest levels of improvement.
Although curcumin shows some clear promise, there is also uncertainty around it. Studies using it for arthritis, cancer, and cognition always find it to be highly safe, and there is ample reason to consider taking curcumin, even if in the end it isn’t proven effective as a memory-enhancing therapy. In particular, its anti-inflammatory and antioxidant activity shows promise for high-risk individuals with ApoE4 genotypes, but that is yet to be proven. For now, I’m going to keep taking curcumin for my joints, with the hope it will protect my brain as well.
Ask your doctor about taking a form of curcumin proven to be highly absorbable. This is crucial. I recommend taking 500–1,000 mg per day for arthritis symptoms or to support healthy brain performance. For information on curcumin products that have been documented to be highly absorbable, visit www.DrMasley.com/resources.
Resveratrol is a compound, normally found in red grape skin and red wine, that has been found to have antioxidant and anti-inflammatory properties. It has also been shown to regulate physiological responses that are similar to those resulting from prolonged calorie restriction (as with fasting), such as a reduction in brain cell inflammation. Taking a resveratrol supplement, however, is much easier than dramatically restricting calorie intake.
A few studies focusing on the immediate impact of taking resveratrol have noted an increase in intracranial blood flow (in other words, more blood circulating throughout the brain—a sign of healthy cognitive function). But I can find only one small study where researchers specifically examined the impact of resveratrol on cognitive performance. In a German study, twenty-three subjects were unknowingly given 200 mg/day of resveratrol and matched with twenty-three who received a placebo. Neuroimaging, blood sugar regulation, and cognitive testing were performed before and after twenty-six weeks of therapy.
Those who received resveratrol showed an improvement in memory, blood sugar control, and functionality of the hippocampus as measured with functional MRI testing. The improvements in memory were highly correlated with better blood sugar control, as measured by testing HgbA1C, a long-term marker for blood sugar regulation. Obviously one small study doesn’t mean we have found a major breakthrough in treating Alzheimer’s disease, but it does give me hope that subsequent studies will continue to show promising results.
An important note on selecting resveratrol supplements: look for labels that say trans-resveratrol. This is the active form of resveratrol. A 250-mg capsule from a bottle labeled with wording such as “standardized to 10% of trans-resveratrol” is only giving you 10 percent of what you need.
As discussed in Chapter 4, one study found that consuming twenty grams of MCT oil daily for ninety days improved cognitive function in people with mild cognitive impairment, though about a quarter of the study participants had gastrointestinal issues with the treatment. Unfortunately, this study showed no benefit for the 20 percent of people who have the ApoE4 gene. In healthy adults, the impact of MCT oil on cognitive function has not “yet” been studied, at least not with published long-term results. The gastrointestinal side effects with this therapy are not serious, just annoying for those who notice them.
I would certainly encourage anyone with any established cognitive impairment to discuss a trial of MCT oil with their own physician.
After one to two weeks, gradually increase to 20 grams daily. If you have gastrointestinal symptoms at this dosage, decrease it to a level you can tolerate, and try to increase back to 20 grams daily in one month. If you suffer from cognitive decline, it would be very helpful if your doctor could order cognitive testing before and after twelve weeks of therapy, so that you can measure results.
Perhaps the most widely marketed supplement on television, radio, and the Internet for preventing cognitive decline is Prevagen, “clinically tested” to improve memory, according to its advertising, often with a table showing a 20 percent improvement in memory. Its active ingredient is apoaequorin, a compound that binds calcium and occurs naturally in jellyfish. But despite its popularity, Prevagen is an example of a questionable supplement—a nutrient cocktail strongly marketed to its target audience but with few studies to back up its brain-boosting claims.
There is only one published study regarding this compound as it relates to protecting against cognitive decline, in the medical journal Advances in Mind-Body Medicine. The authors report a 15 to 20 percent improvement in cognitive function using Prevagen as directed for ninety days, although the benefit was only an extra 3 to 7 percent higher than that of a placebo. Furthermore, in the published article, the authors did not disclose their relationship to the product adequately: they all work for the company that manufactures Prevagen. In my opinion, the list of authors looks more like a corporate board than scientists studying a means to prevent cognitive decline.
Dr. Robert Speth, a noted professor of pharmaceutical sciences, wrote a critical summary about this publication on PubMed (a research tool for scientists), outlining a variety of valid concerns:
• A paid advertisement for Prevagen appeared in the same issue of Advances in Mind-Body Medicine that carried the study, without listing any financial conflict of interest in the article. (This lack of disclosure goes against the norm of most reputable journals and researchers.)
• In terms of how it works in the body and brain, it is unlikely this large a molecule would be absorbed from the gut and less likely that it could penetrate the blood-brain barrier to impact the cerebral cortex. A separate study using apoaequorin in mice noted benefits in protecting against stroke damage only if it was injected directly into the brain itself—in other words, not taken in pill form like Prevagen.
• If apoaequorin was absorbed, Speth indicated, serious side effects might occur. But the authors did not elaborate on any side effects and suggested it was well tolerated.
• The statistical analyses were loaded with flaws and errors. Subjects in this small study went missing, and their absence was not explained; nor was an adequate description of the cognitive testing provided. In light of these anomalies, one would have to consider subjective bias in the conduct of the research and analyses, which was provided by the company selling the supplement.
Perhaps not surprisingly, after Dr. Speth reported his concerns, a class action suit was filed against Quincy Bioscience, the manufacturer of Prevagen. The Food and Drug Administration (FDA) has accused the company of not reporting adverse events, such as seizures, strokes, and worsening multiple sclerosis: more than one thousand incidents have been reported against the product. But to date the company has only followed up on two of these events. The product, as of this writing, is still available for purchase, and the ads continue.
Given all you know about the real causes of memory loss and dementia and how to prevent them, be aware of a questionably vetted product making a too-good-to-be-true claim—in this case, that a single pill or two will quickly deliver a “sharper mind” and “clearer thinking.”
If you or someone you know falls into a high-risk category for dementia and memory loss, or has signs of early cognitive impairment, it is worth learning more about additional supplements that might have benefits. However, I rate the following supplements as less promising than those in Step 2, until further research is available. Some items—like Prevagen (see box “The Problem with Prevagen”)—are aggressively marketed for brain health, but do they really work? We don’t have enough research to say. (In the case of Prevagen, the research seems to be highly flawed.)
Still, the following supplements—coenzyme Q10, phosphatidylserine, huperzine A, and alpha lipoic acid—stand out for their fascinating theoretical possibilities. You’ll notice I don’t include specific Better Brain action steps for these supplements, but still my suggestion is to learn as much as you can about them, discuss them with your physician, and decide if they’re worth adding to your regimen.
Coenzyme Q10 (CoQ10, also called ubiquinol or ubiquinone) is commonly recommended and marketed as a compound to help memory, yet I can find no solid evidence that it improves cognitive function. At high dosages, more than 200 mg per day, it is one of the only agents available that has been shown to slow the progression of Parkinson’s disease. CoQ10 has also been helpful in reducing symptoms for people with congestive heart failure. With extensive study, it has been shown to be very safe and have few side effects.
Because memory loss is associated with decreased brain cell mitochondrial function, and CoQ10 has been shown to improve mitochondrial energy production, in theory it could help prevent memory loss.
In my clinic, the most common reason I recommend CoQ10 to my patients is if they are taking a statin medication for heart disease or cholesterol indications, since taking a statin decreases normal CoQ10 production.
You’ll find a great deal of marketing hype comparing the two forms of CoQ10: the active reduced form, known as ubiquinol, and the oxidized form, which is ubiquinone (the form used in most supplements, and what most research is based on). They interconvert rapidly (meaning that ubiquinol turns into ubiquinone and vice versa), so I don’t see a compelling reason to pick one form over the other, especially if you are asked to pay extra for the reduced form since ubiquinol is generally more expensive.
A major limitation with CoQ10 supplements is their absorption. Tablet forms typically only have 1 percent absorption—it won’t do you much good if it can’t get into your bloodstream. Oil-based capsules should have about 4 percent absorption, while some specially designed forms may achieve 8 percent absorption or more.
If you plan to use CoQ10, be sure to use a highly absorbable form and a high-quality brand. We know that cheap sources, particularly tablets, are not well absorbed, so it’s a better investment to purchase a supplement that is. I’d recommend 50–100 mg daily. If you’re in a high-risk category for dementia and memory loss, it’s important at some point to confirm that you achieve a good level with this therapy, with an adequate dosage to achieve a blood level of >1.0 mcg/ml, or a more optimal level of 1.5–2.0 mcg/ml. Consult with your physician to identify your dosage and blood level.
Phosphatidylserine is a normal component in brain cell membranes, accounting for 14 percent of the phospholipids, a type of fat molecule, in the human brain. It is required for healthy brain cell function. Like fish oil, phosphatidylserine intake nourishes the brain.
It was first isolated from cow brains back in the 1940s, and by the 1980s was used in supplements to support normal brain function. A mad cow disease outbreak (from consuming cow brain) put a stop to nearly all such supplements, and research shifted to synthesizing phosphatidylserine from soy products.
As popular as it has been as a brain support supplement for thirty years, evidence to show that phosphatidylserine improves cognitive function or prevents memory loss is still controversial.
A recent small study conducted in China with fifty-seven patients with established Alzheimer’s disease were randomized to a placebo group or a group receiving 300 mg of phosphatidylserine (produced from a mixture of cow brain and soy products) for twenty weeks. Memory testing was performed before and after dosing. Those receiving phosphatidylserine showed a moderate improvement in memory compared to the control group. The same investigators also performed a similar study in rats, published in the same article, and found that those treated showed lower levels of inflammation in the hippocampus.
One of the limitations noted by the author was that it is unclear if this benefit would persist over the long term or would end after a limited period of improvement. To evaluate the safety of the product, a second pilot study treated thirty older subjects (age range fifty to ninety) with 300 mg per day of phosphatidylserine for twelve weeks. There was no placebo group for comparison. Four of the thirty people (13 percent) dropped out due to GI symptoms (similar to the MCT oil study). After treatment, memory and cognitive function improved, and although otherwise the phosphatidylserine was tolerated without any worrisome effects, we still don’t know if these benefits would be achieved with long-term therapy.
The big controversy with phosphatidylserine as a treatment for memory loss involves its largest study. It compared 300 mg and 600 mg daily of soy-derived phosphatidylserine and placebo for six and twelve weeks of therapy, then used sophisticated measures of memory and cognitive function in 120 subjects with early cognitive decline. The results showed absolutely no benefit of any kind. There was some concern about the quality and shelf life of the phosphatidylserine product used, similar to that surrounding fish oil. (Rancidity may impact effectiveness—or even be harmful.)
Although phosphatidylserine seems safe in short-term studies, until further clinical investigations are performed that confirm its usefulness long term, its effectiveness remains uncertain. But as noted, people with cognitive impairment don’t have the time to wait. If this treatment seems appealing, then check with your doctor to see if phosphatidylserine supplements might be appropriate for you.
Huperzine A is a compound sourced from Chinese club moss (Huperzia serrata), an herb used in traditional Chinese medicine for centuries. In China it’s known for its cognition-supporting benefit and has been shown to be well tolerated in dozens of clinical trials. The limitation with this product, just like most of the other supplement agents discussed, is that none of the studies have yet to show long-term benefit in cognitive function or the ability to prevent memory loss long term.
Studies have shown that in rats, huperzine A inhibits the formation of beta-amyloid protein in the brain. A twelve-week randomized study of seventy-eight human patients with mild to moderate vascular dementia found that those sent to a vitamin C placebo group showed no cognitive improvement, while those receiving a daily dose of 0.2 mg of huperzine A had a modest improvement in Mini-Mental State Examination scores.
A review of twenty randomized clinical trials using huperzine A in a total of 1,823 subjects with dosages from 0.2 mg to 0.8 mg daily suggests that it provides modest improvements in cognitive function and activities of daily living for those with mild cognitive impairment and dementia. But the authors of this review conclude that the current studies are small, that many have flaws in their design or protocols, and that none have yet shown long-term benefits; thus further studies are warranted before they can recommend this promising compound.
It’s worth noting that huperzine A acts just like four of the five drugs approved by the FDA to treat symptoms of cognitive decline. Four are cholinesterase inhibitors, which prevent the breakdown of acetylcholine, a compound that is involved in memory and cognitive function. And although these drugs provide some symptom relief, none of them have been shown to slow the progression of dementia or Alzheimer’s disease. So a limitation is that huperzine A, like those drugs, may provide only short-term symptom relief without stopping long-term decline. (The side effects of these cholinesterase inhibitors are commonly nausea, vomiting, loss of appetite, and increased frequency of bowel movements.) As huperzine A appears to be safe, clarify with your doctor if it is a good choice for you.
Many supplements are designed to support healthy brain function with ingredients that are intended to enhance mitochondrial function. Mitochondria are microscopic organelles that produce the energy that keeps all your cells alive and functioning. Ingredients that enhance them would include items we’ve covered in Steps 1, 2, and 3 for key nutrients, such as fish oil (long-chain omega-3s), curcumin, resveratrol, and CoQ10. If you could boost mitochondrial function, especially in the brain, your brain cells would work better and be less likely to die.
One other agent that gets attention in this category is alpha lipoic acid, a natural compound synthesized in the mitochondria and also supplied in small quantities from the diet, primarily organ meats. Alpha lipoic acid is a powerful antioxidant, has anti-inflammatory properties, improves blood sugar control, and appears to enhance mitochondrial function.
Not surprisingly, many products designed to support brain health include alpha lipoic acid as an ingredient, although due to expense, they may not always provide an adequate dosage to be effective. Is alpha lipoic acid a key nutrient? For now, no studies show that it is effective in preventing cognitive decline, though as a proven antioxidant, it does offer other biochemical benefits. As far as offering brain benefits as part of a supplement, however, the right balance of multiple ingredients featuring this compound has likely yet to be created.
Another way, beyond the nutrients we’ve just discussed, to boost mitochondrial function, increase energy, and rev up cognitive function is exercise, the next pillar of the Better Brain Solution. Getting and staying active with regular exercise can lower your risk for dementia and memory loss.