In Blog, Diet, Exercise, Health, Health Professionals, Lifestyle, multiple sclerosis, Research

Today is the day! My good friend Dr. Dale Bredesen’s book is released to the public. The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope In Their Own Words should give you hope and confidence that patients can overcome this terrible disease.

I am delighted to share an excerpt of the book here with you…

There is an old neuroscience principle: “neurons that fire together, wire together,” meaning that repeated association of input with output strengthens the circuit. In practical terms, this means that repetition will aid in the creation and maintenance of memories, whether these memories are for learning a new language or the use of a new smartphone or a new musical instrument or any of many other learned tasks or information. When we do this learning, we want to optimize all of the contributors, just as when you are building a house you want to have the right blueprints, the best workers, the highest-quality building materials, the proper permits, and so on. So let’s have a look at how we can best build our “house of memories.”

Step one of enhancing your brain is enacting the fundamental protocols we have outlined for preventing cognitive decline: a clean diet, abundant exercise, high-quality sleep, and avoidance of chronic stress. In addition, brain-training programs are both fun and useful for honing your thought process.

Step two of enhancing your brain involves enlisting a personalized array of nootropic (cognitive-enhancing) agents, many of which have multiple mechanisms of action. We have outlined some of the major ones here.

You will want to test, tweak, and adjust your personal protocol as you discover how your own brain responds.

  • Enhancing neurotransmission by acetylcholine: This neurotransmitter is critical for conveying messages between and from neurons. Supplements that may assist its work include huperzine A (derived from Chinese club moss, Huperzia serrata), Bacopa monnieri (also known as brahmi, a traditional Indian medicinal plant), citicoline, alpha-GPC, and lecithin, an essential fat found in many foods, including eggs.
  • Enhancing cyclic AMP: Adenosine monophosphate (AMP) is an important messenger for brain plasticity. Caffeine, an adenosine inhibitor, boosts cyclic AMP, as does L‑theanine, an amino acid found in tea and certain mushrooms.
  • Optimizing glutamatergic vs. GABAergic transmission: Glutamate is the most common neurotransmitter in the body. Gamma-aminobutyric acid (GABA) suppresses excess signaling by neurons. An overabundance of glutamate over GABA is associated with anxiety, depression, restlessness, inability to concentrate, headaches, insomnia, fatigue, and increased sensitivity to pain. You can restore balance with valerian (a medicinal root extract), vitamin B6, and lemon balm, and by taking GABA directly.
  • Supporting mitochondrial function: Mitochondria are the energy production units (organelles) inside the cells of your body. They are critical to cognition and indeed to all metabolism. The goal is to create metabolic flexibility, so that your mitochondria can metabolize either carbohydrates or fats/ketones. Useful supplements include ubiquinol (also sold as Coenzyme Q10, or CoQ10), PQQ (pyrroloquinoline quinone, which increases mitochondrial number), R‑lipoic acid (an antioxidant and enabling molecule also found in spinach and broccoli), ALCAR (acetyl‑L‑carnitine, a metabolism-supporting amino acid), creatine (which provides energy), and nicotinamide riboside—a form of vitamin B3 that increases NAD+ (nicotinamide adenine dinucleotide). Methylene blue holds promise as another method to enhance mitochondrial function.
  • Supporting neurotransmission by dopamine: In the brain, dopamine is a primary signaling molecule that is especially associated with the “reward” pathway that reinforces certain behaviors; loss of dopamine-producing cells contributes to Parkinson’s disease. Supplements that may aid dopamine production include tyrosine and phenylalanine (two essential amino acids), and vitamin B6.
  • Supporting synaptic structure: A healthy brain depends on a robust cellular infrastructure. To help maintain the physical condition of your neurons, try citicoline and its chemical relative, alpha-GPC (glycerylphosphorylcholine), as well as DHA (docosahexaenoic acid), an omega‑3 fatty acid also found in fish, especially cold-water fish.
  • Improving mental focus: Supplements that may help sharpen your thinking include gotu kola (a traditional Chinese and Ayurvedic herb), shankhpushpi (an Ayurvedic medicine), and pantothenic acid (vitamin B5). Many people report success from therapeutic hot/cold treatment, alternating between a hot sauna and cold water to stimulate the sensory response and also enhance mitochondrial function.
  • Enhancing brain-derived neurotrophic factor (BDNF): This essential protein promotes the formation and maintenance of neurons in the body. You can boost your BDNF with whole coffee fruit extract (WCFE) and dihydroxyflavones (7,8‑DHF). There is also a simple and pleasurable technique that boosts BDNF while providing many other physical and psychological benefits—exercise— and there are some enhancements of exercise, such as EWOT (exercise with oxygen therapy) and KAATSU (which uses bands to increase the physiological response to exercise), which may boost exercise advantages.
  • Enhancing nerve-growth factor (NGF): Along with BDNF, NGF is critical to the growth, maintenance, and survival of nerve cells. NGF-promoting supplements include Hericium erinaceus (lion’s mane mushroom), ALCAR, and specific strains of bacteria in the gut microbiome (e.g., some bifidobacteria), which can be boosted by taking probiotics.
  • Enhancing sirtuin 1 (SIRT1): Recent research indicates that this protein stimulates autophagy and provokes an antiaging response in laboratory animals. You can increase SIRT1 function by taking resveratrol (found in grapes and red wine, but also in many berries), nicotinamide riboside, NMN (nicotinamide mononucleotide, a derivative of niacin), and NAD+. You can also stimulate your body’s production of NAD+ with exercise and fasting.
  • Promoting blood flow: Ginkgo has been shown to increase blood flow by stimulating production of nitric oxide, which dilates the blood vessels. Nitric oxide can also be increased by L‑arginine, Neo40, beetroot extract, and arugula.
  • Improving mood: In some cases, you can go straight to the desired effect—and do it without the common drugs that have significant side effects. Saffron is a natural antidepressant; it appears to work by increasing serotonin levels. Lemon balm has also been shown to be effective.
  • Reducing chronic stress: Acute stress, with resolution, is something we all deal with, and it does not impede cognition. However, the unrelenting chronic stress that so many of us experience is associated with brain atrophy. There are many methods to address this, from meditation to yoga to social interactions to music to shinrin-yoku (the Japanese technique of “forest bathing”), and others—whatever brings you joy, relaxation, and fulfillment.
  • Optimizing methylation: Methylcobalamin (Me‑B12, a form of vitamin B12), pyridoxal 5´-phosphate (P5P, an active form of vitamin B6), and methylfolate (another B‑complex vitamin) all regulate methylation, which is critical for the epigenome and its readout of specific genes, as well as for detoxification, among other processes.
  • Minimizing inflammation and supporting adaptive immunity: Inflammation is strongly linked with cognitive decline. Many supplements can help you control inflammation and the effects that come with it. Curcumin (derived from turmeric), ginger, and Withania somnifera (ashwagandha from Ayurvedic medicine) all have been shown to be effective. It is also important to resolve any ongoing inflammation, which can be accomplished with specialized pro-resolving mediators (SPMs) or high-dose omega‑3 fats (2 to 4 grams), and to remove the source of inflammation, whether it be from a leaky gut, metabolic syndrome, chronic infections, or another source. LDN (low-dose naltrexone) is also helpful for optimizing immune function and reducing inflammation. Supporting adaptive immunity includes optimizing zinc (and this is a very common deficiency), vitamin D, and considering quercetin, R‑lipoic acid, and AHCC (active hexose correlated compound).
  • Enhancing detox, minimizing toxin levels: There are many paths to reducing the toxin load in your body. Finding and eliminating sources of toxin exposure is essential, of course. Sulforaphane (found in cabbage and broccoli), glutathione (a common antioxidant), and N‑acetyl cysteine (NAC) help cleanse the body. Eating a high-fiber diet and drinking filtered water will aid you in eliminating toxins. An infrared sauna followed by cleansing with castile soap can also be effective.
  • Healing your gut: An increasing wealth of research has shown unequivocally that your body’s microbial ecosystem is essential to your physical and mental health. The KetoFLEX 12/3 lifestyle incorporates multiple techniques for optimizing your microbiome, including eating a diet rich in fermented foods, plant proteins, and fiber. Reducing your toxin load and minimizing antibiotics and microbiome-suppressing drugs like proton pump inhibitors (PPIs) are also important.
  • Optimizing nutrient status: Beyond the individual supplements, you should strive for overall nutritional balance in your diet. Note, for example, that cognition is better with high-normal levels of vitamin B12 than with mid-normal or low-normal levels.
  • Optimizing antioxidant status: The widespread idea that more antioxidants are preferable is overly simplistic. In reality, you need both oxidant and antioxidant effects, in optimal balance. Depending on your personal biochemistry, you may need to boost your levels of vitamin E, glutathione, vitamin C, sulforaphane, ubiquinol, vinpocetine (a synthetic version of a drug found in periwinkle), and SkQ and mitoquinol (which target the mitochondria).
  • Fasting: Fasting has numerous salutary effects, from enhancing ketosis to improving glycemic control and supporting insulin sensitivity to improving lipid status to improving blood pressure to enhancing autophagy and mitophagy, among others. Thus fasting is the base of the brain food pyramid (at least twelve hours between the end of supper and the start of breakfast or lunch, and at least three hours between supper and bedtime). The earlier in life you begin fasting, the longer and more thoroughly you will reap the benefits.
  • Monitoring: We all now have access to numerous tracking tools, for everything from blood oxygen to ketone level to sleep quality and quantity to heart rate variation, and many others. To tweak your enhancement protocol, you will want to pay special attention to your blood oxygen levels, heart rate variability, ketone levels, glucose levels, sleep quality and quantity, nutrients, exercise timing, and vascular elasticity.
  • Optimizing hormonal status: For most of us, optimizing our diet, exercise, sleep, stress level, and microbiome will allow us to produce highly functional levels of hormones. However, for others, whether due to autoimmunity (for example, Hashimoto’s thyroiditis, which results in reduced thyroid levels) or toxicity or simple carbohydrates or other causes, one or more hormones will be reduced, which can affect cognition. Returning these to optimal with the help of a functional endocrinologist or internist can often help to enhance cognition.
  • Oral health and microbiome: Organisms from the oral microbiome are showing up, quite remarkably, in the brain, in atherosclerotic lesions, and even in cancers, suggesting that there is widespread communication of these organisms throughout the body, including effects on the brain and thus cognition. Optimizing your oral microbiome starts with checking OralDNA testing for pathogens such as P. gingivalis, T. denticola, F. nucleatum, and P. intermedia. If you find that you have significant levels of these pathogens, you can improve your oral microbiome with Dentalcidin toothpaste and mouthwash, followed by a probiotic toothpaste such as Revitin. If you have gingivitis or periodontitis, consultation with an oral-systemic specialist is recommended.
  • Functional genomics: Whole genome sequencing has become very affordable. However, even small fractional genomes, such as the one offered by 23and Me, can be extremely helpful, offering data (with the appropriate evaluation) on ApoE status, Alzheimer’s risk, detoxification (and thus risk for toxin-associated illnesses such as dementia), vascular risk, thrombotic tendency, and many other health parameters.
  • Youth factors: The interest in “young plasma” (heterochronic parabiosis) for aging individuals is still undergoing substantiation, but one of the interesting follow‑up studies showed that the majority of the salutary effects may simply be due to the removal of “aging factors” by plasmapheresis, which would be a much simpler and less expensive alternative. Renewal and re-generation using stem cells has remarkable potential, and ongoing clinical trials (even though carried out as a monotherapy, and thus suboptimally) should help to determine the magnitude of effect these may have on cognition.
  • Short-term interventions: Short-term hyperactivation with agents such as amphetamines, cocaine, or Adderall can certainly enhance cognition, but this comes at a price, since long-term effects such as addiction, fatigue, and vasculitis may ensue. However, there are safer short-term alternatives such as Nuvigil (which inhibits drowsiness and supports alertness) and the racetams piracetam, aniracetam, and phenylpiracetam. The racetams have a nootropic effect, improving memory and cognition, and have few short-term side effects, although some people develop insomnia or anxiety.

Coming possibilities: There are exciting possibilities upcoming, which should continue to advance our ability to enhance cognition: targeted probiotics offer strains that increase specific trophic factors and neurotransmitters; evaluation of the microbiomes of organs thought classically to be sterile—such as blood and brain—should offer new insights into unrecognized organisms impacting cognition (both positively and negatively); CRISPR will allow gene manipulation, with its clear clinical and ethical implications; and retinal amyloid imaging should allow early recognition of amyloid accumulation, which begins to occur about twenty years prior to the diagnosis of Alzheimer’s, thus offering an excellent early warning system.

Optimizing these critical brain parameters will allow all of us to be sharper and stay sharper for decades to come.

This is one book you’ll want in your personal library—pick up your copy today:



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