Executive summary Alzheimer's Disease (AD) is a frightening prospect for those who do not suffer from it, and a horrible reality for those who have a parent with it. Going to a neurologist or gerentologist results in a script for Aricept and being told that the case is hopeless. It isn't.
Dr Bredesen and his research team have uncovered the biochemical processes that cause this form of dementia. The bad news is that AD is an extremely complicated disease, with something like 40 possible contributing causes, and that the treatment protocol is complex, expensive and demanding. The good news is that AD is preventable and, within limits, treatable. It can be reversed.
Bredesen discovered that the buildup of amyloid-beta plaques is not a pathological disease process but a normal defensive reaction in the brain in response to various threats to its health. It is a defensive process, that like cancer, has gone out of control.
As well as uncovering the contributing factors, Bredesen has devised a way to alleviate the effects of every one of them. The protocol for doing this is called ReCODE (Reversing COgnitive DEcline).
The three main causes of AD are 1) inflammation from infection, diet or other causes, 2) decline and shortage of supportive nutrients, hormones and other brain-supporting molecules, and 3) toxic substances such as metals or biotoxins (poisons produced by microbes such as mould). These three classes of causes give rise to the three variants of the disease.
To apply ReCODE it is necessary to determine which variant(s) of AD the person is suffering from and what are the specific factors contributing to cause AD in their case. Then a personalised treatment protocol is devised for the person.
The treatment protocol typically involves extensive testing and major changes to diet, fasting, stress, sleep and exercise. It includes taking many supplements and hormones, plus dealing with toxins and infections. All without drugs.
Disclaimer This summary simplifies the protocols laid out in Bredesen's book. If you wish to seriously use the material then I recommend buying the book and obtaining the support of an integrative (or functional) physician. Alternatively, you may wish to adopt some of the recommendations in order to decrease your risk of AD.
Introduction Currently there exist four medications for Alzheimer's Disease. They may help lessen symptoms but do so only for a limited time. During 2000 to 2010, 244 experimental AD drugs were tested. Only one, memantine, was approved. The effects of this drug are modest at best. AD is the only one of the nation's ten most common causes of death for which there is no effective treatment.
The current dogma, the amyloid-beta hypothesis, is that to treat AD we need to prevent or remove the amyloid-beta plaques that form in the brains of patients with the disease. There are drugs that can do this, but they do not make patients get better, if anything they do the opposite.
AD arises from an intrinsic and healthy downsizing program for the brain's extensive synaptic network. In AD, an otherwise normal brain housekeeping process has gone haywire. The brain suffers some injury, infection or other assault and responds by defending itself. The defence mechanism includes producing amyloid-beta. That's why trying to get rid of amyloid-beta hasn't been helpful in treating AD.
AD is in fact a protective response to three different processes: inflammation, suboptimal levels of nutrients and other synapse-supporting molecules, and toxic exposures. Each of these causes gives rise to a distinct subtype of AD.
The ReCODE protocol can halt and often actually reverse the progress of AD. More than 200 patients have been successfully treated.
ReCODE has not been clinically tested in large studies because it is seen as "too complicated". Medical studies are designed to test a single drug in isolation. Bredesen was unable to have his protocol tested because it does not conform to the standard testing method of a single drug or procedure against a control group. Developing a new drug takes years, if not decades, and costs an estimated $2.5 billion.
A drug called tropisetron, used to prevent nausea in cancer patients, was found to be more effective in mice than the standard AD drugs. Tropisetron blocks four of the 36 known contributors to AD. However, the AD artificially induced in mice is due to a mutation in a protein, and so is unlike 99% of human cases of AD. This limits the usefulness of mouse models of AD and explains why remedies that work for mice do not for humans.
The three main causes of AD AD arises when the brain responds as it should to certain threats. Usually, the defensive response to outside threats succeeds. The problem arises when those threats are chronic, multiple, unrelenting and intense. AD comes about when the brain tries to protect itself from three kinds of threats:
* Inflammation from infection, diet or other causes
* Decline and shortage of supportive nutrients, hormones and other brain-supporting molecules
* Toxic substances such as metals or biotoxins (poisons produced by microbes such as mould)
Amyloid-beta is a potent pathogen fighter but one that eventually goes overboard, killing the very synapses (structures that allow neurons to communicate) and brain cells that it was called upon to protect. So to prevent or reverse AD it is necessary to remove the factors that are causing our brains to defend themselves by producing the amyloid-beta response. Developing the optimal treatment for each person involves identifying the many contributors that are specific to each person, and then fashioning the best programme to target them. The many contributors render the single-pill approach, at best, marginally helpful.
Inflammation is a complex protective response involving immune cells, blood vessels, and molecular mediators. Inflammation can arise without infection. It is triggered when we eat trans fats or sugar. It is also caused by intestinal damage, as when gluten, dairy or grains cause leaky gut, ie microscopic holes that allow food or bacteria into our bloodstream. The immune system thinks these fragments are invaders and attacks. Chronic inflammation arises when we are continuously exposed to dangerous microbes or foods such as sugar.
As well as causing inflammation, sugar toxicity is typically accompanied by insulin resistance, something most Americans suffer from. Humans evolved to handle only about 15 grams of sugar per day, equivalent to 180 ml of soft drink. Sugar is like fire, a source of energy but very dangerous. Our bodies recognise sugar as poisonous and therefore activate multiple mechanisms to reduce its concentration in our blood and tissues, eg storing it as fat, which produces brain damaging factors called adipokines. That leaves lots of glucose in the blood, which attaches to many proteins, severely inhibiting their functioning. Our bodies respond to the flood of glucose by producing more insulin, which reduces the glucose. However, if the body suffers from chronically high insulin levels it turns down the response, ie you become resistant to the effects of insulin.
Insulin is intimately related to AD by multiple mechanisms. After insulin molecules lower the glucose, the body must degrade the insulin in order to prevent blood glucose dropping too low. This is done via Insulin Degrading Enzyme (IDE). IDE also degrades amyloid-beta, but it cannot do both at once. So a critical part of ReCODE is reducing insulin resistance, restoring insulin sensitivity and reducing glucose levels.
To function at its best, the brain needs neuron- and synapse-supporting factors, including certain hormones, trophic factors and nutrients. Brain-derived neurotrophic factor (BDNF) strengthens synapses. BDNF can be increased through exercise and hormones, such as estradiol and testosterone (which in turn are boosted by vitamin D and folate). When the brain runs low on BDNF, it responds by producing amyloid-beta.
Amyloid-beta deactivates toxic metals, such as copper and mercury, as well as biotoxins, such as those produced by moulds. However, it is crucial to prevent the formation of amyloid-beta plaques. Detoxification is aided by cruciferous vegetables, such as arugula, bok choy, broccoli, brussel sprouts, cabbage, cauliflower, collard greens, kale, kohlrabi, maca, mizuna, mustard greens, radish, rutabaga, and watercress.
In AD the underlying disease process is typically ongoing for fifteen to twenty years before a diagnosis is made.
The brains of people who died in their 90s and who had retained excellent memory were examined. Some were riddled with amyloid-beta. It is not known why these brains were functioning well.
The biochemistry underlying AD You can skip this technical section.
Amyloid-beta is toxic to neurons. It acts as an anti-trophin by binding to multiple receptors (protein molecules that receive chemical signals from outside a cell) on neurons, blocking the trophic signalling required to keep the dependence receptors from telling neurons to die. This is how amyloid-beta kills brain cells. In some circumstances, cells are supposed to commit suicide, however, in AD the process spirals out of control.
The process at the heart of AD is the cutting of amyloid-beta precursor protein (APP). After APP is produced by neurons, it is cut by molecular scissors called proteases. The scissors cut at either three spots along APP's 695 amino acids, or at one distinct site.
The cut at three sites produces four peptides, sAPPbeta, Jcasp, C31 and amyloid-beta. All four of these peptides play roles in the processes that underlie AD: loss of the brain's synapses, shrivelling up of part of the neuron, and the activation of the neurons' suicide program.
On the other hand, if APP is cut at just one site then the peptides sAPPalpha and alphaCTF are produced. This pair has effects completely opposite of the quartet above. They are, in short, anti-AD peptides.
Depending on which side of this crucial physiological balance their brain is on, a person will come down with AD or stay healthy. ReCODE is designed to shift the balance in favour of the health-giving cut of APP.
How APP is cut depends (among other things) on whether it binds to netrin-1 or amyloid-beta. Amyloid-beta thus causes the production of more amyloid-beta. This means that amyloid-beta is prionic, ie it generates more of itself without the need for genetic material (which is how cells manufacture all other proteins). So amyloid-beta creates a prionic loop producing ever more brain-destroying amyloid-beta.
APP are long molecules that protrude from neurons and act as receptors. When APP grabs hold of netrin-1, it sends a signal into the neuron that keeps it healthy and functional. When APP fails to grab netrin-1 and lacks other trophic support, it tells the neuron to self-destruct. When APP grabs a molecule of amyloid-beta, it unleashes a cascade of reactions which cause APP to be cut in such a way as to produce more amyloid-beta, causing a downward spiral. In addition, many other molecules tip the balance favourably or unfavourably. These include estrogen, testosterone, thyroid hormone, insulin, vitamin D and many others.
APP is actually a master dependence receptor, integrating the inputs of many different receptors.
When the brain is healthy, synapse-forming and synapse-destroying activities are balanced: we retain needed information and jettison the rest (such as the make of the car we passed before reaching home). As we age, the inputs needed for synaptic growth and maintenance (such as hormones and nutrients) grow more scarce. APP notes this and begins downsizing. In AD the brain is pulling back, preserving only the functions it needs to stay alive, and not expending resources on the formation of memories it doesn't need. Our most cherished and often repeated programs, such as our work and hobby skills, are spared at the expense of new memories. As in corporations that follow a "last hired, first fired" layoff policy, recent memories go first, older ones next, and the oldest ones last.
Dozens of molecules affect APP. This explains why a single drug is never going to stop AD. It is as though our roof has 36 different holes, and the drug fixes just one, or at most a few of these. To remedy AD we need to tip the balance in favour of the anti-AD pathway. To do so we need to plug as many of the 36 holes as possible.
It is well-known that the gene ApoE4 strongly predisposes people to getting AD. As well as reducing the clearance of amyloid-beta, ApoE4 enters the nucleus of the cell and binds very efficiently to DNA. ApoE4 can bind to the promoters of 1,700 different genes, thus having a powerful effect. It quashes several genes that limit inflammation and turbo-charges NF-kappaB, which promotes it. That ApoE4 promotes inflammation was probably advantageous for our forbears. They did not live long enough to contract AD. This trade-off is called antagonistic pleiotrophy, where a genetic alteration enhances fitness early in life at the expense of longevity. Of course, evolution has no interest in the organism's fate after passing reproductive age.
Most people carry two copies of ApoE3, giving a 9% risk of AD. However, 25% of Americans carry a single copy of ApoE4, giving a 30% risk. About 3% carry two copies of ApoE4, lifting the risk to more than 50%.
The three variants of AD
There are actually three distinct varieties of AD: inflammatory, atrophic and toxic.
Type I Inflammatory
This subtype typically begins with a loss of the ability to store new information, while long-term memories and other mental functions remain intact. Type I responds most quickly to the ReCODE protocol. The brain is downsizing synapses.
Type II Atrophic
Like type I, it typically begins with loss of ability to store new memories, while other functions remain intact. Levels of various hormones and vitamin D are usually reduced. Insulin resistance may occur, or insulin levels may be too low. As in Type I, the brain is downsizing synapses.
Type III Toxic
This typically begins with cognitive difficulties involving numbers or speech or organising. Unlike in the other two types, all kinds of memories and skills are at risk of being lost, eg loss of vocabulary, trouble with giving the correct change, and spelling.
The three types correspond to three functions of amyloid-beta. Amyloid-beta is a part of the inflammatory response and can function as an antimicrobial agent, it responds to inadequate levels of nutrients by downsizing synapses, and it protects by binding to toxic metals.
Diagnosis of the causes contributing to AD Bredesen recommends that everyone over 45 should have themselves tested to see whether they are at risk of any of the three subtypes of AD. He advises this for people with no symptoms, as well as for those with Subjective Cognitive Impairment (SCI), Mild Cognitive Impairment (MCI) and AD. Every patient with SCI has improved on the protocol.
It is helpful to measure your cognitive state, which you can do using MoCA, which is available online. A normal score is 26 to 30.
High homocysteine is a contributor to AD types I and II. If you have healthy levels of vitamins B6, B9, B12, and amino acid betaine then your level of homocysteine will remain healthy, ie below 7.
High insulin and high glucose are two of the most important risk factors for AD. When you eat foods with a high glycemic index (GI = the effect on blood glucose) - not just sugars but also starchy foods like white bread, white rice and baked goods - your body pours out large amounts of insulin to keep glucose levels in check, because glucose is toxic at high levels. Cells become insensitive to the constant flood of insulin: when something is ever present you stop responding to it. This contributes to various diseases, including AD, because insulin signalling is one of the most important signals for the support of neuron survival. Also, IDE cannot clean up amyloid-beta if there is too much insulin, as previously mentioned.
Apart from raising insulin levels, high levels of glucose cause four other problems that have a bearing on AD. Fasting insulin, fasting glucose and hemogloblin A1c may be harmfully high.
The link between inflammation and AD is direct. The problem is that the immune system becomes overactive and is chronically activated. This results in cardiovascular disease, cancer, arthritis, accelerated aging, as well as AD. Many assailants can activate the immune system: infections such as viruses, bacteria and fungi; free radicals (reactive forms of oxygen that damage cells, proteins and DNA); advanced glycation end products; trauma such as bruises, sprains and broken bones; and damaged proteins or lipids.
There are four key measures of inflammation: C-reactive protein, the ratio of globulin to albumin, the ratio of omega-6 to omega-3, Interleukin-6 and tumour necrosis factor alpha.
Vitamin B1 (thiamine) is critical for memory formation. Reduced vitamin D is associated with cognitive decline. This vitamin activates some key genes that reduce inflammation and create and maintain brain synapses. Vitamin E is an important protector of cell membranes, which it does by scavenging free radicals. It is one of the very few molecules that has been shown in a clinical trial , as a monotherapy, to slow cognitive decline in AD, albeit modestly.
Hormones are important signalling molecules that regulate bodily functions. Many hormones have an important effect on synapse formation and maintenance.
Optimal thyroid function is crucial to cognition. Thyroid function effects your metabolic speed, determines your heart rate, mental sharpness, reflex speed, and many other health parameters. Most people with cognitive impairment have suboptimal thyroid function. It is important to check free T3, free T4, reverse T3 and TSH.
Estrogen is a crucial factor in the prevention of dementia, as is progesterone. Testosterone also plays a role in both sexes. DHEA is another important hormone that effects cognition.
Stress is one of the most important contributors to cognitive decline. Chronic stress is particularly harmful. Stress causes high levels of cortisol, which is damaging to neurons, especially in the hippocampus, the part of the brain responsible for memory. Pregnenolone is the master steroid hormone from which all others are derived. In periods of high stress, the pregnenolone is siphoned off to produce the stress hormones, leaving too little to produce the optimal levels of sex hormones. In addition, pregnenolone supports memory and is neuroprotective.
Too much copper and too little zinc are associated with dementia. Aging is associated with lower zinc levels, and AD with still lower levels. Zinc deficiency reduces insulin signalling, a critical feature of AD. Zinc deficiency increases inflammation, increases oxidative damage, reduces neurotransmitter signalling and increases sensitivity to toxins.
Magnesium is critical to brain function. Selenium and the peptide glutathione are needed to mop up free radicals.
Mercury from fish or dental amalgams is one of the worst neuro-toxins. Lead, arsenic and cadmium are also toxic to the brain.
Sleep allows cleansing of the brain by allowing more calcium and magnesium ions to flow through. It reduces the formation of amyloid-beta and activates autophagy, whereby damaged mitochondria and misfolded proteins are removed. Sleep is a time of repair and new supportive brain cells are produced. It is important to sleep 7-8 hours per day. However, this may not be enough. Sleep apnia is extremely common, usually goes undiagnosed, and contributes to cognitive decline.
Cholesterol is a vital substance and is not harmful to the brain. What you don't want is damaged cholesterol and its lipid particles.
Gastrointestinal permeability, ie leaky gut, is a very common problem. Ideally, the cells that line the gastrointestinal tract maintain tight junctions that keep food on the correct side, inside your gut. Molecules resulting from digestion, such as amino acids, are then transported into gut lining cells and from there into the bloodstream. The gut can be leaky due to gluten sensitivity, damaging chemicals like those in pesticides, inflammation, chronic stress, yeast or aspirin. If so, then large molecules reach the bloodstream, where they are recognised as foreign, triggering inflammation. Gut porosity also allows other invaders, such as bacteria and yeast to enter the bloodstream. The result is persistent low-level inflammation, and in the worst case scenario, autoimmune diseases such as multiple sclerosis, rheumatoid arthritis or lupus. So it is critical to know your gut permeability.
It is important to test for antibodies, especially those that attack brain proteins, as these are an important contributor to cognitive decline.
A growing list of bacteria, viruses, and fungi have turned up in the brains of AD patients. The presence of low-levels of pathogens is like a cold war, a slow wearing down causing suboptimal functioning. Bacteria such as P. gingivalis can travel from the mouth to the brain. Herpes simplex virus can also migrate to the brain, causing mild but chronic inflammation, characteristic of AD. The AD brain is a veritable zoo of organisms. No single one causes the disease, but all potentially contribute to inflammation. Normally, the brain is protected by the blood-brain barrier, but this can become leaky, like the gut. There is evidence of abnormalities in the blood-brain barrier early in AD. Also, multiple studies have found that there is nasal and sinus access to the brain, a critical determinant of AD type 3. It is helpful to know the status of your blood-brain barrier.
The gut-brain connection is critical for cognition. Although only 5% of people develop celiac disease, most people probably suffer damage to the gut from gluten. Gluten activates zonulin signalling irrespective of gluten sensitivity, leading to increased intestinal permeability. It is important to evaluate gluten sensitivity.
We inhale poisons, we ingest toxins, we absorb toxins through our skins, and we are exposed to toxic electromagnetic fields and radiation. In particular, some widely prescribed cholesterol-lowering drugs called statins tip the APP cleavage in the wrong direction. Mycotoxins made by moulds also cause AD, by causing Chronic Inflammatory Response Syndrome (CIRS). Mycotoxins cause the innate immune system to be activated but the adaptive immune system fails to identify and destroy the invaders, so the innate immune system remains chronically activated. This happens in about 25% of people due to genetics.
Mitochondria supply the energy that allows our cells to function. Many chemicals damage mitochondria including antibiotics, alcohol, NSAIDs (including aspirin) and cocaine.
An unhealthy Body Mass Index (BMI) raises the risk of cognitive decline. For optimal cognition, BMI should be between 18 and 25. Another good indicator of metabolic status is waistline, which should be less than 89 cm for females, and 102 cm for males.
Genes effect your AD risk. It is worth finding out whether you have one or more ApoE4 genes, as the optimal diet differs accordingly.
There is a long list of factors that predispose you to AD: suffering head trauma; having general anesthesia; dental amalgams; eating high-mercury fish; taking certain medicines such as statins, Valium and anti-depressants; using recreational drugs; alcohol; cigarettes; poor oral hygiene; surgical implants; having liver, kidney, lung or heart disease; snoring, as it may indicate sleep apnia; eating trans fats or sugars; having chronic sinus problems; gastrointestinal problems such as bloating or recurrent diarrhoea; constipation; mould; eating processed foods or non-organic foods; tick bites; taking proton pump inhibitors for reflux; using makeup, hairspray or antiperspirant; not sweating much; and not drinking enough purified water.
People who already have symptoms of cognitive decline almost always have between 10 and 25 suboptimal blood chemistry tests. People without such symptoms typically only have three to five. Importantly, each of these values can be returned to a healthy and even optimal value.
General points regarding ReCODE
1) For each abnormality identified, we want to go beyond "normal", all the way to optimal in order to correct the imbalance between synapse preservation and destruction.
2) We want to address as many of the abnormalities as possible. The idea is to patch all 36 holes.
3) For each treatment, the goal is to address the root cause of the problem.
4) The programme is personalised, based on the laboratory values that are abnormal.
5) There is a threshold effect, in that once the balance has been tipped towards synapse maintenance, AD can be halted or reversed. Even though most patients will not follow every Part of the protocol, following enough steps to exceed the threshold is sufficient.
6) The programme is iterative.
7) Drugs may aid the process but are not necessary.
8) The earlier you start the treatment, the greater the chance for complete reversal. This means that no-one should have to die from AD.
9) For just about every element of ReCODE, there is a crutch or workaround, if you need it.
However demanding the protocol may be, anything is preferable to the agonising descent into dementia and death. You need to follow the protocol for about six months to see positive effects.
ReCODE: the treatment protocol to prevent or reverse AD Insulin resistance is probably the single most important metabolic contributor to AD. The best way to overcome this is through diet.
So Part 1 is to optimise your diet. The idea is to produce mild ketosis, where the liver breaks down fat into ketone bodies. This occurs when your body is running low on carbohydrates, switching your metabolism from carbohydrate-burning and insulin resistant to fat-burning and insulin sensitive. Firstly, you eat few carbohydrates and minimal sugar. Minimise bread, white potatoes, white rice, soft drinks, alcohol, grains and processed foods. Minimise foods with a glycemic index above 35. Eating olive oil, coconut oil, avocados and nuts helps ketosis. The best fruits are berries, lemons, tomatoes and avocados. Avoid fruit juices, as they contain no fibre.
The idea is to eat a plant-based diet, with an emphasis on vegetables, especially nonstarchy ones. Eat detoxifying plants such as cruciferous vegetables (cauliflower, broccoli, cabbage, kale, brussel sprouts, arugola), beets, garlic, ginger, avocados, grapefruit, lemons and olive oil. Fermented foods, such as sauerkraut, pickles and kombucha are probiotic (ie contain good bacteria) and hence beneficial. Likewise, high-fibre foods, such as onions, garlic, and leeks are beneficial, as they are prebiotic (ie feed our good bacteria). These must be taken after a course of antibiotics.
Meat consumption should be limited to about 200 gms per day, and preferably not daily. Fish is a good source of Omega-3, but avoid fish such as shark, swordfish and tuna, as these are highest in mercury. Instead, eat salmon, mackerel, sardines and herring.
Gluten is to be avoided because it contributes to leaky gut. Dairy is to be avoided because it causes inflammation. Fibre is essential, as it causes lower absorption of carbohydrates.
Part 2 is to fast for at least twelve hours between your last meal of the night and your first of the next morning. Also, you should finish dinner at least three hours before going to bed. Fasting promotes ketosis and autophagy, a renewal process in which damaged proteins and mitochondria are removed. It is optimal to break the fast with lemon juice and water.
Part 3 is moderate exercise, at least 150 minutes per week of brisk walking. Weight training is also important - 60 minutes per week. More is better. Exercise reduces insulin resistance, increases ketosis, increases the size of the hippocampus, improves vascular function, reduces stress, improves sleep and improves mood.
Part 4 is to train the brain. Hundreds of papers have shown that brain training has important cognitive effects. One speed processing training program, Double Decision (from BrainHQ), nearly halved dementia risk ten years after the training, which is far more than any drug ever has. Bredesen recommends training 15 minutes six times a week.
Part 5 is to optimise sleep. To avoid cognitive decline, or to reverse it, good sleep is indispensable. If you have sleep apnia then it is critical to treat it. The goal is to sleep eight hours per night, without using sleeping pills. Taking melatonin may be helpful. Low levels of progesterone may cause sleep problems. Keep the room as dark as possible and stay away from electric and electronic devices.
Part 6 is to minimise stress. Stress refers to running a system beyond where it was meant to operate. We did not evolve to cope with sugar-laden diets, late nights with incandescent lights, constant anxiety about work, poor sleep, poor nutrition and exposure to hundreds of toxic chemicals. Stress increases levels of cortisol, which at high levels is toxic to the brain. It also increases blood glucose levels, leaky gut and other factors leading to AD. Stress reduction is a critical part of ReCODE. Meditation and yoga are effective. The simplest remedy is to take a few deep, slow, daiphragmatic breaths and relaxing. In addition, it is helpful to discontinue or minimise medications that interfere with cognitive function, such as statins, tranquilisers and anti-depressants.
Part 7 is to reduce homocysteine if it is above 6 micromolar. To do so you should take the vitamins methylcobalamin (B12) and adenosylcobalamin (B12) 1 mgm in total per day, methyltetrahydrofolate (aka folate or B9) 3 mgm/day, and pyridoxal-5-phosphate (B6) 20-50 mgm/day. If homocysteine stays above 6, add 500 mgm daily of glycine betaine.
Part 8 is to take supplements that support cognition. The following are recommended daily: vitamin B1 50 mg, vitamin B3 as nicotinamide riboside 100 mg, vitamin B5 150 mg, vitamin D 2500 IU, vitamin E 800 IU, vitamin K2 as MK7 100 mcg, acetyl-L-carnitine 500 mg, ashwagandha 500 mg twice daily, bacopa monieri 250 mg twice daily, citicoline 250 mg twice daily, CoQ10 as ubiquinol 100 mg, curcumin 1 gm twice daily, gotu kola 500 mg, hericium erinaceus (lion's mane) 500 mg, liposomal glutathione 250 mg twice daily, magnesium threonate 2 g, omega 3 DHA 1 gm and EPA 750 mg, polyquinoline quinone 15 mg, resveratrol 100 mg, shankhpushpi (aka shankhapushpi or skullcap) 2 capsules, zinc picolinate 40 mg.
Part 9 is to diminish inflammation, which is critical to reversing cognitive decline. There are three steps: 1) Resolve the existing inflammation by taking Specialised Pro-resolving Mediators (SPMs), such as SPM Active. 2) Inhibit new inflammations by taking Omega-3, curcumin, ginger, cinnamon, cloves, thyme, green leafy vegetables, beets and broccoli. 3) Remove all sources of inflammation, such as leaky gut, too much sugar, trans fat, and chronic infections, such as Lyme disease.
Part 10 is to heal the gut, a key tactic in reversing cognitive decline. If you have food sensitivities, bloating, constipation or loose stools, you are likely to have leaky gut. Step 1 is to eliminate the causes, such as sugar, gluten sensitivity, allergies, pesticides, alcohol, anti-inflammatories (eg aspirin, steroids) and stress. Step 2 is to take bone broth or capsules, such as colostrum or L-glutamine, or follow a Specific Carbohydrate Diet (SCD). Your gut should be healing after about four weeks. If it has healed then Step 3 is to include prebiotics and probiotics.
Part 11 is healing any infections in the nose or sinus, as these can severely impact the brain. The culprits are often moulds or bacteria such as MARCoNS. Treatment is by nasal spray. Then you need probiotics for the nose. Finally, any mould in your environment needs to be removed.
Part 12 is balancing your hormones, as these are essential to cognitive functioning. Thyroid functioning is suboptimal in many people with cognitive decline. Estradiol and progesterone have powerful effects throughout the body, including the brain. Optimal levels of testosterone support brain health. Pregnenolone is the master steroid, from which other important hormones are derived. Hormone replacement is a controversial area and expert medical knowledge is needed to balance your hormones. It is important to use bio-identical hormones, not imitators.
Part 13 is metal homeostasis. Mercury is a powerful trigger of AD in a minority of patients. If your mercury is high, it is helpful to remove amalgam fillings and replace them with ceramic ones. It is important to do this using a special process that does not expose you (or the dentist) to harmful mercury vapours. It is also important to remove mercury from your tissues using chelation or pulsed treatments that activate a gene that helps the body to eliminate mercury.
The zinc to copper ratio should be about 1:1, if not, you should raise your zinc levels.
Part 14 is addressing biotoxins. All mould should be removed and a mobile HEPA filter is helpful. There are also supplements and detoxifying vegetables, as mentioned above.
If ReCODE is not working, the most likely explanation is that people skip parts of the protocol and leave out critical elements. The main "side effect" of ReCODE is overall better health, including improved insulin sensitivity, better lipid profile (state of your blood), more energy and better mood. It is often accompanied by weight loss.
There is a website called ApoE4.info, where people share their successes in combatting AD.