Can this Anti-Alzheimers nutrition and supplementation enhance brain function for normal people?

What more likely to work — a Limitless pill or a comprehensive program to maintain a healthy brain? An N=1 biohacking experiment.

Marc-Olivier Jodoin via Unsplash

What we get done in life largely depend on how we make decisions, how we persuade and how we execute. These things stem from our minds and our brains—the quality of our software and our hardware.

My upbringing and education focused on training the mind: knowledge, wisdom, pattern-recognition, emotional self-mastery, mental models. Is this also your experience? History had the same bias. Ancient philosophers to 20th century psychologists neglected brains in favor of minds.

It is likely that this is simply due to technology. Our ability to see the physical inner-workings of the brain is very recent. For instance, these physiological techniques for managing emotions only came about in the past few decades:

14 Tools for Better Work and Relationships from the Neuroscience of Emotions

Brain optimization is also in its infancy. Silicon-Valley-type biohackers are ingesting everything from coconut oil, to cacao to microdoses of psilocybin, just to get an edge in productivity and creativity.

These are called nootropics, substances that enhance brain function. Despite the new name, the practice is ancient. Our ancestors have been consuming coffee, tea and tobacco for their nootropic effects. Humanity has been in constant search for the Limitless pill.

If we liken the brain to a car, what should you focus on to increase its performance? Testing out different kinds of superfuels or ensuring each part is in optimal condition?

The biggest investments on brain research has been for the search for the cure to Alzheimer’s disease. Interestingly, the search for a pill has been the biggest strategic disappointment in Alzheimer’s research.

Could the approach of fixing each component of the brain work better than a pill with a single target? This is the solution presented in The End of Alzheimer’s, the bestselling book by Dr. Dale Bredesen, MD.

In this post, I relay the nutrition approach and supplements recommended by the book, and I share my plan of doing an N=1 using these. In the appendix, I decide how trustworthy this book and its author are.

For the science, the history, and the results, please refer to the book, or these:

• Dr. Dale Bredesen on Preventing and Reversing Alzheimer’s Disease — interview with Dr. Rhonda Patrick
• Case studies by Dr. Bredesen

(Motivations beyond brain optimization: years ago, I lost my grandmother to Alzheimer’s long before she passed away. Today, many in my family — including my mother— are entering their senior years. Could this approach lessen the risks of cognitive decline, or at least delay it?)

The trio appears again

One reason for my interest in this approach is my experience with mental optimization through nutrition. A couple of years ago, I started using the ketogenic diet for productivity. It is still one of my most effective productivity techniques.

Since experiencing the productivity gains from keto, I have doubled down on this domain. Around half the books and articles I’ve read, and the podcasts I listened to since then, were about health and nutrition. In my deep-dive into this world I encountered the following trio again and again. They also appear in the book:

• Sleep
• Exercise
• Nutrition

Just wanted to put that out there. I will revisit sleep and exercise in the future. For now, let me focus on nutrition.

Nutrition Guidelines from The End of Alzheimer’s

The nutritional approach promoted by the book has three broad strokes: it is ketogenic, flexitarian and incorporates fasting. They call this the Ketoflex 12/3 diet.

• It is ketogenic — which means it is low-carbohydrate, moderate protein and high in fat. Why? “Mild ketosis, it turns out, is optimal for cognitive function: beta-hydroxybuterate increases production of the important neuron- and synapse-supporting molecule BDNF (brain-derived neurotrophic factor), among other effects.” A quick check in PubMed shows that there are lots of research on using the ketogenic diet for Alzheimer’s disease:

Nerds: knock your self out at Pubmed

• It is flexitarian — which means it is largely plant-based, with an emphasis on vegetables, particularly non-starchy ones. Meat is treated as a condiment, not the main course (max of 1 gram per kg of bodyweight per day).
• It incorporates fasting — the book suggests at least 12 hours of fasting per day, which contributes to ketogenesis.

Details include:

• When eating carbs, chose those with low glycemic index (below 35) — mostly non-starchy colorful vegetables with lots of fiber. The worst are simple carbs like sugary drinks (most sodas and juices), most baked treats, and breakfast cereal.
• Fruits are optional, but if you’re going to eat some, go for whole fruits, not juices.
• The worst combination: when simple carbs meet saturated fat and lack of fiber (eg, cheeseburger, fries and soft drinks).
• Avoid gluten and dairy. Gluten is implicated in leaky gut and dairy causes inflammation which some people can’t handle.
• Eat detoxifying plants like “cilantro, cruciferous vegetables (cauliflower, broccoli, various types of cabbage, kale, radishes, Brussels sprouts, turnips, watercress, kohlrabi, rutabaga, arugula, horseradish, maca, rapini, daikon, wasabi, bok choy), avocados, artichokes, beets, dandelions, garlic, ginger, grapefruit, lemons, olive, and seeweed.”
• Good fats: avocados, nuts, seeds, olive oil and MCT oil.
• Whole foods, not processed foods
• The book also warns against the mercury content of large fish — it suggests SMASH instead: salmon, macarel, anchovies, sardines and herring.
• Probiotics and prebiotics: kimchi, sauerkraut, sour pickles, miso soup, kombucha, jicama, onions, garlic, raw leeks, raw Jerusalem artichoke, dandelion greens. Helpful yeast: Saccharomyces boulardii.
• Digestive enzymes: if you experience acid reflux, if your lab values indicate inflammation, if you are under chronic stress, if you have reduced stomach acid, or if you are older than 50.

Supplementation recommended by The End of Alzheimer’s

Dr. Bredesen recommends these “daily for everyone with cognitive decline or risk for cognitive decline, unless their laboratory values are optimal for each parameter.”

• Vitamin B1, 50mg (important for memory formation)
• Pantothenic acid (Vitamin B5), 100–200mg (especially if focus or alertness is an issue)
• B6/B12/folate combination (as described in the book for conversion of homocysteine to methionine or cysteine) for those whose homocysteine is above 6
• Vitamin C, 1g, for those with suboptimal vitamin C levels or who have copper:zinc ratios greater than 1:2
• Vitamin D, starting with 2500 IU per day, until serum levels reach 50 to 80
• Vitamin E as mixed tocopherols and tocotrienols 400–800 IU, for those with vitamin E levels less than 13
• Vitamin K2 as MK7 100mcg, for those taking vitamin D
• Resveratrol 100mg, for all.
• Nicotinamide riboside, 100mg, for all.
• Citicoline, 250mg tice per day, to support synaptic growth and maintenance
• ALCAR (acetyl-L-carnitine), 500mg, to increase levels of nerve growth factor
• Ubiquinol, 100mg, to support mitochondrial function in everyone.
• Pyrroloquinoline quinone (PQQ), 10 to 20 mg, to increase mitochondrial number for everyone
• Omega-3 fatty acids
• Whole coffee fruit extract (WCFE), 100mg once or twice per day for three months, then withdraw slowly over one month. This increases BDNF.

Herbs that support synaptic function

• Ashwagandha, 500mg, twice per day with meals. This helps in the reduction of amyloid, as well as handling stress.
• Bacopa monnieri, 250mg, twice per day with meals, to improve cholinergic function, one of the brain’s key neurotransmitter systems.
• Gotu kola, 500mg twice per day with meals, to increase focus and alertness.
• Hericium erinaceus (lion’s mane), 500mg once or twice a day, to nerve growth factor.
• Rhodolia, 200mg once or twice per day, for those with anxiety and stress.
• Shankhpushpi (skullcap) taken 2 or 3 teaspoons or 2 capsules per day, to enhance branching of neurons in the hippocampus.
• For those with the toxic type of Alzheimer’s (see book), mild cognitive impairment (MSI) or subjective cognitive impairment (SCI), tinospora cardilifolia (guduchi) is helpful to boost immune support. It is taken at a dosege of 300mg with meals, 2 or 3 times per day. Along with boosting immune support, consider guggul, which removes toxins in the gut, typically taken as capsules of guggul extract, 350 or 750mg per day.
• For those with the inflammatory type of Alzheimer’s (see book), MCI, SCI, or with bowel symptoms, triphala — a combination of of amalaki, haritaki, and bibhitaki — is useful to reduce inflammation. This is best taken on an empty stomach, either as a capsule or by making tea from powder.

If you follow the Ketoflex 12/3 diet and still have insulin over 4.5, hemoglobin over 5.5% or fasting glucose is over 90, try these one at a time and measure again:

• If your zinc levels are below 100, try 20mg to 50mg of zinc picolinate daily, then recheck glucose after two months
• If your RBC magnesium is less than 5.2, try magnesium glycinate (500mg per day) or magnesium threonate (2g per day)
• 1/4 teaspoon of cinnamon, sprinkled on food or as 1-gram capsules to improve glycemic control
• Alpha-lipolic acid is an antioxidant— 60mg to 100mg daily
• Chromium picolinate lowers blood glucose — 400 micrograms to 1mg daily
• Berberine lowers blood glucose — 300 to 500mg 3 times per day

N=1 Plan

• First, I’ll measure my baseline cognitive performance using one of the apps recommended here: https://www.braintropic.com/how-to-properly-track-the-effectiveness-of-nootropics/
• Next, I’ll start taking each supplement and measure daily mental performance
• Output: supplement, price, local availability, mental performance measurement, subjective notes. Decide on a regimen moving forward.

If you’d like to do this together with me, email me at bio@corazo.org.

Appendix 1: Should I trust Dr. Dale Bredesen, MD?

I’m serious about measuring trustworthiness when it comes to nutrition and health. I have a list of 25 mental models I use.

Mental Models for Nutrition and Health

For this book and this author, let’s use the following:

• What do people I trust say?
• What are the top criticisms and who are the top critics?
• Probabilistic upsides and downsides

What do people I trust say?

On one hand, Rhonda Patrick had him in her podcast and she seems to trust him.

On the other hand, Peter Attia casually mentioned in his Alzheimer’s prevention episode with with Richard Isaacson that his team looked at the references that the Bredesen protocol is based on and discovered that the conclusions of about 30% did not actually support the part of the protocol it referred to. Dr. Attia mentions Resveratrol in particular. However, when I checked the book or this 2016 case study by Dr. Bredesen et al, I could not find references for Resveratrol. I’m a paying member of his podcast, so I’ll ask about this in the member-only Q&A.

(If you really want to get into the weeds of measuring trustworthiness in pop heath, check out this criticism of Matthew Walker’s Why We Sleep. Peter Attia appears be a bigger advocate for Walker than Rhonda Patrick is for Bredesen. Just putting this out there to show how complex and multi-dimensional this is.)

What are the top criticisms and who are the top critics?

First, let’s look at Dr. Bredesen’s background from a pro source:

• “internationally recognised as an expert in the mechanisms of neurodegenerative diseases”
• MD from Duke University Medical Center
• Chief Resident in Neurology at the University of California, San Francisco (UCSF)
• NIH Postdoctoral Fellow at Nobel laureate Stanley Prusiner’s laboratory at UCSF
• Faculty positions at UCSF, UCLA, and the University of California, San Diego
• Directed the Program on Aging at the Burnham Institute
• Founding President and CEO of Buck Institute
• End of Alzheimer’s is a New York Times Bestseller

Here are the top results when searching for “End of Alzheimer’s criticism” or “End of Alzheimer’s scam”:

• Harriet Hall, MD, a retired army surgeon who has a column about quackery and alternative medicine in Skeptic magazine, includes Dr. Bredesen in her review of Alzheimer’s doctors and researchers interviewed in a series of paywalled videos by Peggy Sarlin (book version). Dr. Hall concludes that there is no consensus among the doctors interviewed, and that they are making false claims.
• Orac (David Gorsky, MD, PhD) who considers functional medicine to be quackery, asks whether the Bredesen protocol is “functional medicine on steroids.” He highlights the shortcomings of Bredesen’s publications and his undisclosed conflicts of interests.
• Some pros and cons at Quora. Cons highlight the lack of proof. Pros feel the protocol warrants some consideration, given the initial results and the lack of alternatives.

Here’s my estimation of this bet:

• My experience has convinced me that lifestyle (mainly sleep, exercise, nutrition) have a huge impact on cognition.
• The downside is that this will cost some money. There appears to be minimal health risks.
• The upside is that I could have a better-functioning brain, for a longer span, and could potentially help my loved-ones also extend their cognitive health span.

I think this is worth doing an N=1.

If you want to do this together with me, email me at bio@corazo.org