Super Human

by Dave Asprey

  MICRODOSE NICOTINE

  More recently, I’ve been using oral nicotine for cognitive enhancement. Hear me out. I am not talking about cigarettes or vaping or any tobacco product. Nicotine is only one of many chemicals in cigarettes, and by itself it is a smart drug with few side effects.

  A 1988 pilot study demonstrated the pronounced effects of nicotine on the brain in Alzheimer’s patients.22 After six patients received intravenous nicotine, cognitive tests revealed decreased memory impairment, as well as fewer mood-related disturbances like anxiety and depression. More recently, a double-blind pilot clinical trial revealed that six months of a 15 milligram daily dose of nicotine is beneficial for those with milder forms of cognitive impairment.23 And the body of research is growing. Nicotine may also help those with Parkinson’s and Alzheimer’s due to its ability to work as an antioxidant in the brain.24

  Nicotine affects peroxisome proliferator-activated receptor gamma coactivator 1-alpha (better known as PGC-1 alpha), the master regulator of mitochondrial biogenesis. This means that nicotine actually helps grow new mitochondria. This is the same anti-aging mechanism as exercise! In fact, one reason so many people gain weight when they quit smoking is because of the decrease in PGC-1 alpha. Yes, you read that right: Nicotine creates some of the same changes in cells as exercise. (Do both!)

  I first became aware of this research in 2014 and have been using low-dose nicotine (1 milligram, which is about 5 to 10 percent of what’s in a cigarette) for cognitive enhancement ever since. Along the way, I had to ask myself if I was okay with being addicted to nicotine—after all, it is an addictive substance—and I decided that I am. What if I told you I did something every day that made me feel good and if I stopped doing it I felt worse? You might call me an addict. The problem is that I’m talking about exercise! I don’t consider it a weakness to be addicted to something that helps me perform better. I’ve come across lots of people who are only comfortable being addicted to the same things as everyone else, like air and water and maybe coffee. That’s their prerogative, but it might mean they’ll age just as quickly as everyone else, too.

  Like modafinil, nicotine is not appropriate for anyone under twenty-five. You need a fully baked brain before you start messing with this stuff. And keep in mind that if you use nicotine, you’ll have to check a box on your life insurance saying that you use it, or else abstain for ninety days. Also, it’s important to take a minimal dose—while low doses can be helpful for aging and cognitive performance, high doses of nicotine are harmful for mitochondria and may even cause hair loss or erectile dysfunction.

  While it hasn’t been studied, the strategy that makes the most sense is low-dose (1 to 2 mg in divided doses) occasional use for cognitive enhancement starting at twenty-five and moving up to 1 mg two to three times per day up to age fifty, and adding another 1 mg per day approximately every five to ten years. In other words, when you’re seventy, you might be up to 10 to 12 mg. That’s about what you’d find in one cigarette.

  If you do decide to try nicotine, be careful which products you use. Don’t smoke or vape. Use oral (spray, gum, or lozenge) products instead. I’m a fan of the start-up Lucy, which makes nicotine products with clean ingredients and no industrial artificial sweeteners.

  Let me be clear one more time: Smoking will not make you Super Human, help you live longer, or ever provide you with a positive ROI. Vaping is better than smoking, but the ROI is also negative. Just don’t do it.

  MICRODOSE DEPRENYL

  One of the most powerful anti-aging smart drugs available is selegiline, also known as deprenyl. It is mostly known for stimulating production of dopamine, an important neurotransmitter that is involved in emotions, pleasure sensations, and the brain’s reward and motivation mechanisms. Dopamine also helps control movement, which explains why nerve cell damage leading to a dopamine deficiency causes symptoms of Parkinson’s disease such as tremors and loss of balance.25

  There is a fine line between too much dopamine and too little. Too little is clearly problematic, but too much is associated with some pretty severe symptoms such as aggression and paranoia. Luckily, the amazing human brain has a mechanism in place to keep your dopamine levels in check. You naturally produce an enzyme called monoamine oxidase B, or MAO-B, that eats up extra dopamine in the brain.26 If you don’t have enough MAO-B, your dopamine levels climb, but if you have too much MAO-B, your dopamine tanks. This can leave you unmotivated, unable to feel pleasure, and withdrawn. On top of that, excess MAO-B puts surrounding cells in harm’s way because its process of destroying neurotransmitters releases aging free radicals.

  Unless you’re dealing with neurological or psychological issues, the MAO-B checks-and-balances system normally serves you well until about age forty-five, which we typically think of as our peak. Around then, your MAO-B levels begin to rise year over year, which means dopamine starts to break down faster than you can replenish it. This is why most elderly people unfortunately have low dopamine levels.27

  Selegiline/deprenyl works by blocking the enzymatic activity of MAO-B, which slows this breakdown of dopamine. To treat early-stage Parkinson’s disease, doctors prescribe high-dose selegiline in pill form along with dopamine precursors. Together, they make extra dopamine and block the enzyme that destroys it.28 There are also selegiline patches that doctors use to treat depression.29

  In addition to blocking MAO-B, selegiline increases neurotrophic factors, compounds that strengthen existing neurons and support the growth of new neurons. Selegiline also increases superoxide dismutase, a powerful antioxidant that breaks down harmful substances in cells. This helps prevent tissue damage that can lead to hardening of the arteries, heart attack, stroke, and other inflammatory conditions.30 These two effects are the reason I’ve been a fan of microdose deprenyl for twenty-two years.

  Doctors have known about the longevity benefits of selegiline since the 1980s. Back then, a handful of animal studies showed that giving rats selegiline led to measurable life-span increases.31 Rats that were given selegiline also became better learners,32 and one study showed that giving rats selegiline restored behaviors that are typical of younger rats.33 That’s why I like it!

  Keep in mind that selegiline interacts with other psychoactive medications and some over-the-counter medicines like dextromethorphan (an ingredient in some cough suppressants) and the plant medicine ayahuasca. At the normally prescribed doses, there are also possible physical and mental side effects such as nausea, sleep disturbances, impaired movement control, changes in heart rate, confusion, and more. These stem from having too much dopamine in your system. If you’re starting with good dopamine levels, are young, and are supplementing with excess selegiline, you might experience side effects without benefits.

  This is a prescription drug, and a functional medical doctor or anti-aging doctor will usually prescribe 1 mg per day (about a tenth of a high dose) starting in your thirties, and increase the dosage by 1 mg for every decade of age after that. In addition to the anti-aging effects, many users notice positive changes in motivation, energy, and concentration.

  COENZYME Q10/IDEBENONE

  Your mitochondria use coenzyme Q10 to produce energy. We all naturally have coenzyme Q10 in our bodies, but when you have extra free radicals and oxidative stress (you know, aging!), your mitochondria will use up your coenzyme Q10, leaving you with a deficiency. In addition, several pharmaceutical drugs, such as cholesterol-lowering statins, can reduce blood levels of coenzyme Q10 by up to 40 percent.34 Supplementing with coenzyme Q10 can help offset this decrease and provide you with more energy by helping your mitochondria work better.

  If you plan to live longer than you’re supposed to, CoQ10 must be on your short list of supplements at 100 to 200 mg per day. Advanced anti-aging experts often recommend idebenone, a synthetic pharmaceutical that is similar to coenzyme Q10 and is shown to improve skin and help brain cells stay healthy35 and improve learning and memory in mice.36

  PYRROLOQUINOLINE QUINONE (PQQ)
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  This antioxidant is about a hundred times as powerful as vitamin C at protecting your cells from free radicals to keep them young. It also stimulates NGF, which helps you grow new neurons, and has been found to enhance the regeneration of peripheral nerves that connect the brain and spinal cord to the rest of the body.37 You can find PQQ naturally but not in useful levels in many foods such as green tea, fermented soy (natto), spinach, parsley, and (sadly, often inflammatory) green peppers.38

  Research on mice supports PQQ’s ability to kick mitochondria into high gear. Specifically, it can increase mitochondrial density to provide more energy,39 reduce inflammation,40 boost metabolism,41 combat oxidative stress,42 improve fertility,43 improve learning and memory ability,44 and protect the heart.45

  PQQ also activates PCG-1 alpha in the same way that exercise and nicotine do, which sparks mitochondrial biogenesis.46 This means that one supplement can enhance your existing mitochondria and help you grow new ones, all while acting as an incredibly powerful antioxidant. It’s pretty much the holy grail of longevity. So why is no one talking about it?

  There are two types of PQQ: stabilized disodium salts and active PQQ. Several years ago, I started taking 30 to 40 mg of the salt form of PQQ every day. However, unlike when I took other mitochondrial energizers, I never felt any effect. It’s possible that it was doing something, but I couldn’t detect a difference. PQQ is an expensive supplement, and I’m now convinced I was wasting my money and time on it.

  The likely reason I didn’t feel any energy even from large doses over an extended period of time is that it is sold as the “stabilized” disodium salt form because it’s more convenient for the manufacturer. Unfortunately, in humans, disodium salts precipitate when they are exposed to even small amounts of stomach acid. That means that all that expensive PQQ I took was turning into little rocks in my stomach instead of helping my mitochondria. To get around that, I wrapped PQQ molecules in a protective coating of oil called a liposome to help them absorb. That is how the Bulletproof supplement ActivePQQ was born.

  If you don’t use the liposomal form, you could try taking PQQ salts on an empty stomach, possibly with some baking soda to neutralize stomach acid. There are no studies supporting this technique, but I bet it works.

  L-THEANINE

  This is an amino acid found in green tea that increases BDNF,47 the growth factor that makes your brain more plastic. On its own, L-theanine promotes relaxation,48 alertness, and arousal.49 L-theanine also works synergistically with caffeine, so it’s pretty convenient that it’s found in green tea. Together, the two increase reaction time, memory, and mental endurance.50 You can supplement with L-theanine or drink a cup or two of green tea per day.

  If you decide to try green tea, look for one that’s grown in the shade. Shade-grown green tea typically has much higher levels of chlorophyll, amino acids, and L-theanine than other varieties. This also increases the amount of caffeine in the tea and the sweetness of its flavor.

  LION’S MANE MUSHROOM (HERICIUM ERINACEUS)

  This staple of traditional Chinese medicine supports the brain and nervous system and promotes mental clarity, focus, and memory. These mushrooms are high in antioxidants and stimulate NGF. In fact, an isolated biopolymer in lion’s mane was found to be more effective than NGF or BDNF in protecting neurons from oxidative stress.51 I take this in combination with the other supplements that boost NGF and BDNF for the highest possible ROI.

  There are different ways of extracting lion’s mane mushrooms, and hot water is not a great one. That’s why I don’t recommend lion’s mane capsules or tea, and it tastes horrible in coffee. The most effective form I’ve ever tried is a double extract that uses both alcohol and heat, made by Life Cykel. Two droppers before bed create noticeable increases in my REM sleep with powerful dreams I can easily remember.

  CURCUMIN

  A 2018 study52 out of UCLA confirms that a daily dose of curcumin—the active ingredient in turmeric—improves memory and mood in people with age-related memory loss. In the double-blind, placebo-controlled study, forty adults between the ages of fifty and ninety who complained of memory issues were assigned to one of two groups. Group one received a placebo, while group two received 90 milligrams of curcumin twice daily for eighteen months. All forty participants took standardized cognitive assessments at the study’s inception and then at six-month intervals. Thirty of the participants also underwent positron emission tomography (PET) scans to monitor brain amyloids before starting and then again after eighteen months.

  The results revealed that the participants who took curcumin experienced markedly improved memory and attention abilities. In fact, the people taking curcumin improved their memory scores by an average of 28 percent over eighteen months. This group also noted mood improvements, and their brain PET scans showed less amyloid buildup.

  To reap curcumin’s maximum longevity benefits, take it in supplement form. Pair it with bromelain (a digestive enzyme found in pineapple), or take it in an oil-based capsule to increase your body’s ability to absorb and utilize curcumin. Do not fall for the mistake of using black pepper or bioperine to increase absorption. Black pepper extract absolutely does raise your levels of turmeric and many other polyphenols. The only problem is that it does it by interfering with cytochrome P450 3A4 liver detox, which you need to stay young. That liver pathway cleans out pollutants, and by messing with that detox pathway, black pepper extract prevents your body from clearing potentially harmful compounds. So you end up with higher levels of turmeric and higher levels of aging toxins, too. This is not a good strategy. Black pepper extract has also been linked to leaky gut syndrome,53 so I strongly recommend skipping it.

  When I created the Bulletproof curcumin formula, I paired curcumin with a little-known Chinese herb called stephania root and frankincense to further help with inflammation, and I used oil-based capsules for absorption instead of black pepper. (Yes, I invest in creating things I believe in!)

  HE SHOU WU (POLYGONUM MULTIFLORUM)

  This ancient Chinese herb originally appeared in Taoist texts as a longevity enhancer. Now we know why. It stimulates the body to produce superoxide dismutase, an incredibly powerful antioxidant. It also inhibits MAO-B, increasing dopamine levels in the body54—kind of like deprenyl.

  I started taking He Shou Wu a few years ago because of its ability to restore hair growth and reduce grays. Yes, most of my anti-aging hacks focus on feeling rather than looking young, but it’s okay to want to look good. Most of my relatives went gray before they were thirty, and I noticed my own hair starting to turn gray when I was in my thirties, along with a slightly receding hairline. There are a handful of studies to show that He Shou Wu helps rats regrow hair,55 and it’s been considered one of the most effective ways of restoring color to gray hair since ancient times.

  In fact, He Shou Wu translates to “He’s black hair.” According to legend, the man who discovered this herb took it every day and went from being completely gray to having a full head of lustrous black hair. He also allegedly lived in good health to a hundred and sixty. Since taking He Shou Wu, I have noticed my grays reducing, but I also take other supplements that help. I expect to regrow a full head of black hair and maintain a fully functioning brain when I’m a hundred and eighty.

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  Bottom Line

  Want to age backward? Do these things right now:

  •Keep your blood sugar stable, even after meals, by reducing sugar intake. Extra sugar causes oxidative stress you don’t want. If you do eat sugar or carbs, pair them with fiber or saturated fat. Extra points for adding chromium and vanadium supplements to control blood sugar spikes.

  •Develop metabolic flexibility with a cyclical ketosis diet to fuel your brain and keep your neurons from becoming insulin resistant.

  •Make sure you have low levels of ketones present in your body much of the time, but not all the time. I use Brain Octane Oil, especially when I eat carbs.

  •Consider neurofeedback treatmen
t if you’ve experienced significant trauma or suffer from symptoms of anxiety or depression. You’ve got to get that fixed, or it will tax you for the rest of your life.

  •Try a cognitive enhancer from the list in this chapter to promote healthy brain function and avoid cognitive degeneration as you age. Here is the short list:

  •Piracetam: Reduces cognitive decline with age

  •Modafinil: Performance enhancing, not anti-aging

  •Nicotine: Low doses (not from cigarettes) can be helpful for aging and cognitive performance

  •Deprenyl: Works on dopamine receptors for cognitive enhancement

  •CoQ10: Helps your mitochondria produce energy

  •PQQ: A powerful antioxidant for anti-aging

  •L-theanine: An amino acid that helps with memory and mental endurance

  •Curcumin: Improves memory and attention while acting as an antioxidant

  •He Shou Wu: Longevity-enhancing antioxidant herb that can also help you regrow and regain color in your hair!

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  7

  METAL BASHING

  When I was in my mid-twenties and suffering from symptoms of aging ranging from arthritis to cognitive dysfunction, I was lucky to find a doctor who was experienced in identifying heavy metal toxicity. I tested positive for high levels of mercury and lead and probably had significant amounts of other metals in my body, too. This may sound shocking, but really the only surprising thing was that I knew about these metals, not that I had them. If you’re alive and reading this there is a very high likelihood that you have dangerous levels of toxic metals in your body, too. Even worse, “safe levels” of toxic metals aren’t safe at all if your goal is to get younger.

  If you’re young and resilient, you may not yet feel the effects of heavy metals. But make no mistake; if they are present in your body, they are impacting you in subtle ways. Imagine again that you’re Superman, and someone has sprinkled kryptonite everywhere on Earth. It’s in the soil that grows your food, in the water supply, and so on. Little by little, you consume small amounts of this poison. It doesn’t kill you right away—it just lessens your powers. Every time you ingest it, you’re a little bit weaker.