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2/15/2025 0 Comments

Time-Restricted Eating and the Gut Microbiome: Health Implications

Time-restricted eating (TRE) is a highly promising dietary approach that improves health outcomes in part by modifying the gut microbiome. Recent research is revealing how the timing of meals affects our microbial communities and, in turn, our health (Pérez-Gerdel et al., 2023).

Impact on Microbial Composition
Studies show that TRE can significantly change gut microbial ecology, though these changes return to baseline when the intervention stops (Pérez-Gerdel et al., 2023) suggesting that TRE is a lifestyle and not a one-time intervention. Research has documented several key changes in bacterial populations, and these appear particularly important for metabolic health and obesity resistance (Zeb et al., 2023; Ribas-Latre et al., 2024).

Some details:
- Increased Bacteroidetes and Prevotellaceae
- Decreased Escherichia, Shigella, and Peptostreptococcus
- Enhanced cyclical variety in metabolically important bacterial families
- Reintroduction of beneficial Ruminococcaceae, including Oscillibacter species
- Increased Lachnospiraceae, Parasutterella, and Romboutsia with 12-week TRE
- Enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron in shorter interventions like Ramadan fasting

How TRE Works
Time-restricted eating improves metabolic markers through the production of beneficial compounds, regulation of daily rhythms, control of metabolism, and effects on immune function (Ribas-Latre et al., 2024).

Bile Acid Signaling
TRE works partly by changing bile acid signaling, which is involved in most aspects of health, from glucose regulation to liver function, and immune competence. Lactobacillus bacteria, which increase with TRE, produce enzymes that modify bile acids, affecting both metabolism and heart health (Zeb et al., 2023).

Metabolic Control
TRE influences metabolism through several mechanisms:
- Early-day eating reduces insulin levels throughout the day (Longo & Panda, 2016) which would be expected to reduce diabetes risk;
- Changed bacterial populations affect brain signaling through glucocorticoid pathways (Luo et al., 2018);
- Microbiome changes alter metabolic signaling molecules (Sonnenburg & Bäckhed, 2016), which alters how diet impacts glucose and lipid regulation.

Health Benefits
Cardiovascular Health: Recent studies show clear links between TRE-induced microbiome changes and improved heart health markers (Zheng et al., 2024).

General Health: Research shows promising effects from research in mice. TRE can:
- Increase protective bile acids like TUDCA
- Improve gut barrier function Increase protective goblet cells in the gut
- Reduce inflammatory cytokines in the blood

Eye Health: In mice, these changes brought about by TRE protect against diabetic eye disease (Beli et al., 2018) and may reverse age-related eye changes (Huston et al., 2024)

Stroke Protection: Changes in the microbiome caused by TRE can reduce stroke damage in animal studies (Delgado Jimenez et al., 2021).

Clinical Considerations (in humans): Several key factors affect TRE's success:
- Duration: Brief interventions (8-hour fasting) may not sufficiently change the microbiome in people with obesity (Guo et al., 2021).
- Individual Differences: Response to TRE varies significantly between people.
- Timing: Early-day eating appears most effective for metabolic benefits (Ribas-Latre et al., 2024).

Conclusion
Evidence strongly supports TRE's ability to beneficially modify the gut microbiome and improve health markers. The only thing holding me back from enthusiastically recommending that everyone adopt a TRE lifestyle is that some studies have shown loss of muscle mass. This was seen for instance in a study of individuals fasting 16 hours per day, and eating between 12 noon and 8 PM. Thus the TRE for them was both short and late in the day (Lowe et. al, 2020).

I have a tip: if you have chosen to eat within a short window (because you are trying to keep calories down) a bit too late in the day, make sure you engage in resistance training. You can gain muscle mass on TRE when you are engaged in strength training. In a 2021 study (Kotarsky), TRE subjects lost more weight than control subjects. TRE subjects gained 0.5% muscle, while control subjects gained 1.9%. The difference was not statistically significant, and neither group lost muscle mass.

In another study, young men assigned to TRE (and strength training) made improvements in muscle strength (though not muscle size) that were sometimes superior to that of the subjects who were eating normally (Tinsley).

So we can improve on Michael Pollan’s excellent health advice “Eat food. Not too much. Mostly plants.” And “stop early in the day.” But watch your muscle mass because all the research is not in.

REFERENCES
Beli E, Yan Y, Moldovan L, et al. Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice. Diabetes. 2018.

Cuervo L, McAlpine PL, Olano C, Fernández J, Lombó F. Low-Molecular-Weight Compounds Produced by the Intestinal Microbiota and Cardiovascular Disease. Int J Mol Sci. 2024.

Delgado Jiménez R, Benakis C. The Gut Ecosystem: A Critical Player in Stroke. Neuromolecular Med. 2021.

Guo Y, Luo S, Ye Y, et al. Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients. J Clin Endocrinol Metab. 2021.

Huston CA, Milan M, Vance ML, et al. The effects of time restricted feeding on age-related changes in the mouse retina. Exp Gerontol. 2024.

Kotarsky CJ, Johnson NR, Mahoney SJ, Mitchell SL, Schimek RL, Stastny SN, Hackney KJ. Time-restricted eating and concurrent exercise training reduces fat mass and increases lean mass in overweight and obese adults. Physiol Rep. 2021 May;9(10):e14868.

Li F, Armet AM, Korpela K, Liu J, Margain Quevedo R, Asnicar F, Seethaler B, Rusnak TBS, Cole JL, Zhang Z, Zhao S, Wang X, Gagnon A, Deehan EC, Mota JF, Bakal JA, Greiner R, Knights D, Segata N, Bischoff SC, Mereu L, Haqq AM, Field CJ, Li L, Prado CM, Walter J, et al. Cardiometabolic benefits of a non-industrialized-type diet are linked to gut microbiome modulation. Cell. 2025.

Li L, Yang K, Li C, et al. Metagenomic shotgun sequencing and metabolomic profiling identify specific human gut microbiota associated with diabetic retinopathy in patients with type 2 diabetes. Front Immunol. 2022.

Liu W, Wang C, Xia Y, et al. Elevated plasma trimethylamine-N-oxide levels are associated with diabetic retinopathy. Acta Diabetol. 2021.

Longo VD, Panda S. Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan. Cell Metab. 2016.

Lowe DA, Wu N, Rohdin-Bibby L, Moore AH, Kelly N, Liu YE, Philip E, Vittinghoff E, Heymsfield SB, Olgin JE, Shepherd JA, Weiss EJ. Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial. JAMA Intern Med. 2020 Nov 1;180(11):1491-1499. Erratum in: JAMA Intern Med. 2020 Nov 1;180(11):1555. Erratum in: JAMA Intern Med. 2021

Luo Y, Zeng B, Zeng L, et al. Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus. Transl Psychiatry. 2018.

Pérez-Gerdel T, Camargo M, Alvarado M, Ramírez JD. Impact of Intermittent Fasting on the Gut Microbiota: A Systematic Review. Adv Biol (Weinh). 2023.

Ribas-Latre A, Fernández-Veledo S, Vendrell J. Time-restricted eating, the clock ticking behind the scenes. Front Pharmacol. 2024.
Shi B, Li H, He X. Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation. Gut Microbes. 2024.

Sonnenburg JL, Bäckhed F. Diet-Microbiota interactions as moderators of human metabolism. Nature. 2016.

Tinsley GM, Forsse JS, Butler NK, Paoli A, Bane AA, La Bounty PM, Morgan GB, Grandjean PW. Time-restricted feeding in young men performing resistance training: A randomized controlled trial. Eur J Sport Sci. 2017 Mar;17(2):200-207.

Zeb F, Osaili T, Obaid RS, et al. Gut Microbiota and Time-Restricted Feeding/Eating: A Targeted Biomarker and Approach in Precision Nutrition. Nutrients. 2023.

Zhao Y, Qiu P, Shen T. Gut microbiota and eye diseases: A review. Medicine (Baltimore). 2024.

Zheng Y, Wang J, Liu M, Zhou X, Lin X, Liang Q, Yang J, Zhang M, Chen Z, Li M, Wang Y, Sui J, Qiang W, Guo H, Shi B, He M. Time-restricted eating with or without a low-carbohydrate diet improved myocardial status and thyroid function in individuals with metabolic syndrome: secondary analysis of a randomized clinical trial. BMC Med. 2024

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1/5/2025 0 Comments

January 05th, 2025

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10/21/2024 0 Comments

WHAT YOUR BACTERIA WANT YOU TO KNOW

It's been 34 years since I graduated from medical school, so I’ve seen quite a few ideas come and go. In my opinion, the two most exciting advances in our understanding have been the discovery of the microbiome and of epigenetics.

We now know that bodies change on a daily or even hourly basis via processes that are potentially reversible: the modification of gene expression (epigenetics), and the modification of a factory of organisms living within us. This collection of microscopic organisms is called “microbiota.” The collection of all their genetic material is the “microbiome.” Estimates are that 30-50% of the substances circulating in our bloodstream are made by bacteria.

HOW DISEASE DEVELOPS

These minute-to-minute changes in our gene expression and microbiota, if they keep going in the same direction over time, result in the symptoms of a variety of conditions. To the extent these changes are reversible, the array of symptoms they result in, which we call “diseases,” are also reversible, unless much damage has been done.

This may be easier to understand for anyone who has tried to tend a garden: the same plant in two different spots, say one with direct sun, and one in the shade, will look entirely different. If you notice this within a few weeks of putting your plant in the ground, you can move the plant and save it. If you wait too long, the plant may not survive. It’s easy to see in plants because they have “continuous embryogenesis,” that is, they never stop developing. It’s harder to see in humans because we look fairly unchanged from the outside. But on the inside, our immune system and endocrine system set the tone best suited to the moment.

What tells our immune system what the tone should be? It’s done by turning certain genes on , and other genes off. This is also known as modification of gene expression (our genes as well as microbial genes). The signals come from our changing gut bacteria, the food we eat, the activities we engage in, how much sleep we get, the events that occur in our lives and how we interpret them in light of everything that has come before, and the impact of toxins from the environment. Each of these affects all other aspects, and each impacts gut bacteria, which as I just remarked, make 30-50% of the substances in our blood: these substances get to work changing the immune and metabolic characteristics in ways we are barely beginning to understand.

Thus the task is to get to the root cause of a problem in order to reverse this problem. We target diet, exercise, sleep, stress, events, and toxins, and in turn that modifies our gut bacteria. Much of conventional medicine uses medications meant to modify our own biochemistry, and that has proven quite useful, but too often does not restore us back to a state of health.

HOW TO IMPROVE GUT BACTERIA

So the question is how to impact our microbiota, given that they have such broad impacts. Clearly, diet, stress reduction, exercise, sleep, and toxin exposure will play a role. A recent article by leading gut researchers at Stanford (see article by Wastyk et. al. below), including Erika and Justin Sonnenburg, describes a 10 week intervention where subjects were instructed to either double the amount of fiber in their diet, or drastically increase their intake of fermented foods. The researchers thought that if they could modify the microbiota, they might find improvements in the immune system and metabolic markers (glucose regulation for example, or blood pressure and cholesterol).

To their surprise, adding fermented foods worked much better overall than increasing fiber. Their conclusions were that too many people don’t have a good enough microbiome (the bacteria in their gut between them do not have enough genes) to make proper use of the added fiber. A few people in the study were indeed able to make use of the fiber (as evidenced by whether there were undigested carbohydrates in their stool, or not) and those people got an anti-inflammatory boost from the fiber.

However, in the fermented food section of the study, 10 weeks was sufficient to improve microbiota diversity. The new bacteria acquired were not mostly from the fermented foods themselves. They were from elsewhere in the environment, but the fermented foods were somehow able to help them thrive. The subjects in the study consumed about 6-7 portions of fermented foods each day. One portion is equivalent to 6 oz of kefir, yogurt, fermented cottage cheese, 1/4 cup of kimchi or sauerkraut, or 2 oz of fermented brined vegetable juice.

In a side experiment (see video referenced below), the Sonnenburgs gave some people probiotic capsules to see if supplements (like the bacteria in the fermented foods) would result in a more diverse microbiome with anti-inflammatory benefits. They found that this was the case only for a minority of participants. Probiotics were beneficial only in the subset of people already consuming lots of vegetables and fruit. Thankfully, that does describe the majority of our functional medicine patient population, but it doesn’t necessarily fit most of the American public. This second experiment with the probiotics wasn’t published so I can’t comment on which probiotics were used, or how much benefit was derived compared to eating fermented foods.

Now that we know this, we can have some fun creating and consuming a wide range of fermented foods. We can circle back to raising the fiber in our diets when we get some better bacteria as a result.

FERMENTING

The simplest foods to ferment at home are from the cruciferous vegetable family. Many recipes are available online and in books on fermentation (a couple of books I liked are listed in the references below). Cabbage, cauliflower, kohlrabi, turnips, daikon radish, and others just need to be cut up, mixed with salt, and massaged for a few minutes. Liquid will appear as you do that, and you can stuff them into a jar below the level of the liquid if you push hard enough (usually). Then they need to be weighted down, with a glass weight, or a sterilized rock (boil it for 12 minutes). Finally, you want to place a permeable lid (I like airlock lids that let gases out but not in), and keep the mixture at room temperature, 60-75 F, for a few days. Taste them once a while and decide when they are done. You can add other vegetables to the mix, or ferment just carrots, onions, cucumbers, etc., but you’ll have to find recipes that tell you how much salt to use, and which starter culture to add. If you also add hot peppers, you can make kimchi.

Fermented drinks are also quite simple to make. You can place grated ginger and raw unprocessed sugar in a jar and leave the mixture at 70-80 F for a few days, feeding it additional sugar and ginger daily. This will create a “ginger bug” and you can use some of the liquid to make bubbly gingery drinks, while keeping the “bug” going over time.

If you purchase (or obtain from friends) a “symbiotic colony of bacteria and yeast” (SCOBY), either milk kefir grains, water kefir grains, or a kombucha SCOBY, you can turn milk, water, coconut water, nut milks, or tea into fermented drinks. The first fermentation (1-21 days, depending on the preparation and temperature) isn’t very bubbly, but then you can ferment your drink further in a sealed container (“second fermentation”), at room temperature, for 1-2 days, maybe adding fruit and herbs, to increase the carbonation and flavor. In other words, there is an endless world of creativity out there! The kefir grains and SCOBY are living organisms, so you have to figure out what to do with them to keep them healthy between making batches of fermented drinks.

One more option: fermented vegetable tonics. This is vegetable juice such as carrot or tomato juice or a mix, fermented at 65-75 F with the addition of brine from a previous ferment, for 3 days. This produces a highly nutritious drink — just 2 ounces constitutes a portion of fermented foods. There’s also beet kvass, which is cut up beets soaked in salt water for a few days. This can also be secondary-fermented into a more complex and bubbly drink.

HUGE VARIETY

Of course there is also yogurt, cultured cottage cheese, cultured cream, and butter. A recent report revealed that many commercial products do not contain the probiotics they claim to contain. Making these products at home could be one solution to this problem.
Meats can be fermented (salami, corned beef), as well as grains. Soybeans and other legumes, and hot peppers and garlic can be fermented into useful sauces. It’s truly endless. There’s even a book about fermenting wild radish seed pods and cattail stems.

With the Holidays almost upon us, we naturally think about all the multiple roles of food, nourishment, tradition, togetherness, celebration, and delight. It can be a good time to venture into learning about the playful art and science of fermentation.

REFERENCES
Fermented: A Four-Season Approach to Paleo Probiotic Foods — Ciciarelli

Mastering Fermentation: Recipes for Making and Cooking with Fermented Foods — Karlin

Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021

Video: https://www.youtube.com/watch?v=s3MZjgtvEQ8
Using Diet as a Lever to Improve Your Microbiome: Erika SonnenburgI

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10/21/2024 0 Comments

October 21st, 2024

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7/26/2023 1 Comment

Avoiding Antibiotics

The Journal of the American Medical Association (JAMA) this week has 2 articles on avoiding antibiotics for childhood sinusitis.

One is a research article showing that there is no difference in the rate of symptom improvement unless the culture is positive for either Strep pneumonia or Hemophilus influenza, and only about 50% of the cases have one or the other of these.
It also reveals that the color of the nasal discharge is no help in telling us whether there will be any response to antibiotics.

The accompanying editorial goes further in saying that even when there is improvement, this improvement is not striking: it might be a slight decrease in the duration or the cough frequency, and in return, you get all the drawbacks of an antibiotic course. Read further for tips on avoiding antibiotics in several different situations.

Tips for Avoiding Antibiotics

By now, we’ve all heard that we need to try to avoid antibiotics. But did you know that at least 50% of all antibiotic prescriptions are unnecessary? This conjures up images of bored tired careless time-pressed doctors, but I think that is the wrong image. I think a lot of well-educated people who are otherwise getting good care are ending up on too many antibiotics because doctors don't have enough other tools.

The illnesses for which antibiotics are often not needed range from a variety of upper respiratory infections (bronchitis, sinusitis, pharyngitis and otitis), to skin infections, and perhaps urinary tract infections. In functional medicine, we almost always focus on improving the gut microbiome. Thus, I am often disappointed when, in the middle of trying to improve their inflammation, my patients unnecessarily end up on antibiotics!

The list of where antibiotics don’t help just keeps growing. We know of several conditions where antibiotics just set you up for the next infection by eliminating the beneficial bacteria that keep things in check.

Here’s what I would do for some common conditions:

1. Sinusitis

There is no evidence that antibiotics make a difference here. Whenever a study is done comparing different antibiotics and placebo, no difference is detected. Yet so many of my patients swear that they would get extremely sick if they didn’t have their antibiotics. So since sinusitis is a viral illness (unless you have a fever of 102.5); and since you can’t kill bacteria before they develop (resistant ones would develop in their place); here’s what I would like people to try before filling a prescription: an antiviral regimen. Purchase a bottle of Sambucol (NOT Sambucus) from Amazon ahead of time and keep it in your house in case you get a virus. At the first sign that you are coming down with a cold, take a dose of Sambucol and call me for a full antiviral protocol: it involves large doses of vitamin A, vitamin D, and other supplements. Let’s try to nip this in the bud and give you some strategies for the future.

2. Ear infections

While these are very painful, about 99% of them resolve on their own, and that is also true in most children. I like to use ear drops with garlic and mullein, and if the infections are frequent, look for an underlying cause of allergies, such as food intolerance, or a history of water damage in the home.

3. Skin infections

The first line of treatment for a break in the skin (a cut or abrasion) should be careful cleansing with soap and water, and very quick scrubbing of the area to remove dead skin. It is very hard for bacteria to infect live skin, but they go for those leftover bits if you are too gentle. Then elevate the area if appropriate, to prevent excessive swelling and give infection-fighting cells a chance to get to the wound.

4. Bronchitis

This is also almost always viral. The exception is for chronically ill people, such as long-time smokers with chronic bronchitis, who can get their diseased lungs infected with bacteria. The rest of us just get cough with phlegm (that is the definition of bronchitis). It does not matter whether the phlegm is clear, creamy, yellow or green – it’s all viral (rust or blood requires investigation). Make sure you drink plenty of water to keep phlegm thin so you can cough it out more easily. If you get bronchitis often, let’s look for an underlying source of inflammation. I know from personal experience that improving your overall health can eliminate bronchitis from your life completely. But please avoid antibiotics.

5. Bladder Infections

These are very common. They start with feeling like you need to urinate frequently, and a sensation of burning when urinating. Many women know to quickly get started on some cranberry concentrate, but don’t have any additional tools. When the cranberry fails, too many rush to their primary care provider, or even call and get a prescription over the phone. If you are at risk of urinary tract infections, please call me and let’s have a short visit. There are several treatments that would be appropriate for non-pregnant adults.

So are they placebo?

While the effect of unnecessary antibiotics could simply be placebo, it does seem like it could be something else when so many people swear by them. One theory I have is that antibiotics make people feel better by changing the mix of gut bacteria. Perhaps there are other ways of accomplishing this! Get some rest; change your diet; take probiotics?

And in case you are wondering what else is overprescribed, here’s a list from the “Choosing Wisely” campaign, which attempts to improve the quality of care by physicians

7. Conjunctivitis: most pinkeye is also viral

8. Back pain: steroids do not work

9. Back pain again: MRIs rarely change management

10. Reflux in babies: antacids almost never work

11. Medications to bring down fever: almost never needed

12. Antibiotics for prevention of complications (for the dentist for example) when patients have mitral valve prolapse

13. Routine antacids to prevent ulcers in hospitalized patients

I hope this helps you keep your personal collection of beneficial bacteria happy and thriving!

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7/20/2023 1 Comment

Unconventional Longevity

What might be a functional medicine approach to extending the "healthspan?"

Dr. Peter Attia, well-known to people interested in cutting edge science related to longevity, recently published his first book, Outlive, now a non-fiction New York Times best seller. The book is receiving mostly high praise on Amazon and Good Reads.
At this point, most people know the basics of longevity:

eat your vegetables
exercise regularly
treat known conditions
do preventative testing
don’t smoke

We also understand that we want to live not only longer, but also be as healthy as possible hopefully until the end.
Conventional medicine has long taught that there are actionable ways to avoid an early death. Public health has supported “health promotion and disease prevention,” and sets periodic goals for individual preventive services. The US Preventive Services Task Force publishes guidelines after reviewing the latest evidence. A service needs not only to be effective in reducing the harm from a certain disease, it also needs to not cause significant additional harm.

Medicine 3.0

I admit I have not read Outlive, but I have been a faithful listener of 250 or more of Attia's podcasts, since the first one came out in 2018. I am very familiar with his outlook and recommendations.
Attia introduces the concept of “Medicine 3.0.” The idea is that Medicine 1.0 is what happened when we found effective treatments for acute illnesses. Medicine 2.0, which is what most doctors are practicing, addresses chronic illness with certain medications. It also recommends certain diets (for example, the DASH diet for hypertension), and admits that sufficient exercise, stress reduction, and sleep are relevant to avoiding and managing chronic conditions. By Attia’s definition, Medicine 3.0 would build on its precursor by integrating advances in technology, data analytics, and systems biology to deliver truly personalized and precision medicine. Medicine 3.0 would leverage digital health technologies, artificial intelligence, and predictive analytics to optimize health outcomes and enable earlier detection and intervention. Under this banner, Attia also promotes the concept of “healthspan" extension, aiming to prolong healthy and functional life by targeting the underlying mechanisms of aging and age-related diseases.

Interestingly I don’t think this type of medicine is available, many of the tests may be used in research settings but not in clinical settings, and only a few people can afford all the high tech tools, some of which have no proven net benefit. Accordingly, the most common critique of Outlive appears to be that it fails to give practical information.

Functional Medicine and the Healthspan

Attia is not trained in functional medicine, and what he recommends overlaps with but does not encompass all of functional medicine. For example, I have never heard him or any of his podcast guests mention that an “elimination diet” meant to improve the quality and quantity of gut bacteria can powerfully impact cholesterol, including his favorite metric, the apolipoprotein B. But I have observed this repeatedly in my practice. It is almost a surprise when it doesn’t happen. To be fair, there does not appear to be research on this, but I learned it from my teachers in functional medicine.

So as I scanned the several hundred reviews of Attia’s book, I wondered how the functional medicine approach to longevity and the health span would be different. The only study of longevity (actually using the Horvath clock as a proxy for longevity) showed that a specific diet (“Younger You”) resulted in the subjects becoming 3 years younger on average, after an 8-week diet change (Fitzgerald et al, 2021).

Functional medicine has called itself “21st Century Medicine.” The emphasis on lifestyle, systems biology, and abundant lab work is present in both functional medicine and Medicine 3.0.

However, functional medicine also emphasizes the following, and Attia fails to do so, in spite of the fact that there is reasonable evidence for their importance:

Environmental toxins are playing a significant role in ill health, and this is gaining mainstream recognition (Lamas et al, 2023). We are exposed to neurotoxins, immunotoxins, endocrine disruptors, and carcinogenic substances. These need attention.
Many people have inadequate nutrients. While conventional medicine focuses on a few (B12, iron, sometimes vitamin D), and Attia mentions folate and magnesium, we have good evidence for the importance of optimizing several others, including omega 3s, zinc, copper, calcium, coenzyme Q10, and DHEA (see references)
We can improve gut bacteria and biomes throughout the body; there is definitely enough actionable clinical research on this (Wastyk et al, 2021)
We can and should improve intestinal permeability; I don’t remember Attia ever discussing “leaky gut” though it is understood to be a cornerstone problem (Fukui, 2016)
We need to look for and target common persistent infections: for example Herpes simplex 1 (cause of cold sores) is related to Alzheimer’s disease, and treating with antivirals when appropriate likely reduces the risk of dementia (Lopatko Lindman et al, 2021)

A practical proposal

So I would like to propose Medicine 2.5/Functional Longevity: something that uses the science we have, and the tools that are presently available to us, to design a root-cause, personalized approach to longevity and healthspan:

Start with a complete patient history
Add US Preventive Services Task Force recommended testing (mammography, colonoscopy, and more depending on age and sex and risk factors)
Add basic blood testing that insurance normally covers, as justified by pre-existing conditions
Add self-pay testing, depending on interest and level of evidence, including: levels of certain key nutrients, blood and urine heavy metal levels, levels of antibodies to certain common infections that might tell us whether they are still too active, and other actionable markers
Consider microbiome testing: it is in development, but it is an option that can be explored. At any rate, some of the research-proven ways of improving the microbiome can be undertaken even without testing.
Use available Medicine 3.0 tools, like the continuous glucose monitor, body composition DEXA scan, and the continuous monitor for heart rate variability, to gain insight into these important parameters
Individualize diet recommendations
Learn stress reduction tools: heart rate variability (HRV), a marker of stress, is related to many diseases and to survival itself. So we should be well-versed in ways to improve HRV. We have an option for continuous HRV measurement.
Use low tech interventions optimally: overnight fasting is one such intervention. Attia does not recommend fasting for longer than 14 hours due to possible muscle loss. That is definitely something that can be individualized. Another is the fasting-mimicking diet: a tool for improving cholesterol levels, insulin resistance, and overall, favorably altering the microbiome to improve symptoms of various autoimmune diseases, and also response to chemotherapy (Longo et al, 2021)
Individualize exercise. Attia spends a lot of time exercising, including several hours weekly in Zone 2 training (moderate intensity steady-state cardio). On the other hand, Stacy Sims, PhD, an exercise researcher who specializes in women’s physiology, says that Zone 2 training is not so important for postmenopausal women, while other types of exercise take on more importance. Too much exercise reliably brings on low heart rate variability, a risk factor for many diseases.
Pay close attention to additional systems biology approaches, such as sufficient stomach acid, to make sure the stomach can serve all the roles it specializes in; dental care, hearing testing, eye care — senses are an important part of keeping the brain cognitively healthy.

The Root-Cause Approach

When it comes to the core parameters of longevity, functional medicine takes more of a root-cause approach than I ever hear discussed in Attia podcasts. Or sometimes, an approach that leverages the body’s pre-existing pathways to health. Here are some key parameters to optimize when aiming for a longer healthspan, and how one would address them using a root-cause approach. None of these work for everyone, and some should only be attempted after other steps have been taken.

1. Blood pressure: diet, exercise, elimination diet, stretching, nitric oxide supplements — and of course medication if all else fails. Treated hypertensives are never as healthy as normotensive people
2. High LDL or high apolipoprotein B: diet, exercise, fasting-mimicking diet, elimination diet, fiber, consider the impact of saturated fat, or the impact of carbohydrates
3. Homocysteine: B vitamins, elimination diet, omega 3 supplements
4. Glucose and insulin/insulin resistance diet, exercise, sleep, elimination diet, fasting-mimicking diet, stress reduction, improving HRV, increasing plant-based foods, ketogenic diet — it really depends on the person
5. VO2 Max: coenzyme Q10 and other mitochondrial nutrients, exercise
6. Bone health: calcium, vitamin D, exercise, diet, sleep, homocysteine, gluten-sensitivity, leaky gut and inflammation
7. Colon health: optimize gut bacteria, diet, exercise, elimination diet, probiotics, fermented foods, fiber (but in what order? That is dependent on the individual)
8. Muscle mass: exercise, diet (enough protein), reducing inflammation, sleep
9. Improving sleep: monitoring HRV, supplementation, making practical changes to sleeping environment and to preparation for sleep
10. Overweight: fasting-mimicking diet, 13-14 hour overnight fasting, elimination diet, exercise, toxins
11. CPR and other markers of inflammation: elimination diet, probiotics, sleep, stress reduction, exercise, cur cumin or anti-inflammatory herbs.

MORE DETAILS ON OUR UNCONVENTIONAL LONGEVITY PROGRAM HERE.

REFERENCES

https://pubmed.ncbi.nlm.nih.gov/33844651/
Fitzgerald KN, Hodges R, Hanes D, Stack E, Cheishvili D, Szyf M, Henkel J, Twedt MW, Giannopoulou D, Herdell J, Logan S, Bradley R. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY). 2021 Apr 12;13(7):9419-9432. doi: 10.18632/aging.202913. Epub 2021 Apr 12. Erratum in: Aging (Albany NY). 2022 Jul 27;14(14):5959. PMID: 33844651; PMCID: PMC8064200.

https://pubmed.ncbi.nlm.nih.gov/29922669/
Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflamm Intest Dis. 2016 Oct;1(3):135-145. doi: 10.1159/000447252. Epub 2016 Jul 20. PMID: 29922669; PMCID: PMC5988153.

https://pubmed.ncbi.nlm.nih.gov/37306302/
Lamas GA, Bhatnagar A, Jones MR, Mann KK, Nasir K, Tellez-Plaza M, Ujueta F, Navas-Acien A; American Heart Association Council on Epidemiology and Prevention; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; and Council on the Kidney in Cardiovascular Disease. Contaminant Metals as Cardiovascular Risk Factors: A Scientific Statement From the American Heart Association. J Am Heart Assoc. 2023 Jul 4;12(13):e029852. doi: 10.1161/JAHA.123.029852. Epub 2023 Jun 12. PMID: 37306302.

https://pubmed.ncbi.nlm.nih.gov/35310455/
Longo VD, Di Tano M, Mattson MP, Guidi N. Intermittent and periodic fasting, longevity and disease. Nat Aging. 2021 Jan;1(1):47-59. doi: 10.1038/s43587-020-00013-3. Epub 2021 Jan 14. PMID: 35310455; PMCID: PMC8932957.

https://pubmed.ncbi.nlm.nih.gov/33614892/
Lopatko Lindman K, Hemmingsson ES, Weidung B, Brännström J, Josefsson M, Olsson J, Elgh F, Nordström P, Lövheim H. Herpesvirus infections, antiviral treatment, and the risk of dementia-a registry-based cohort study in Sweden. Alzheimers Dement (N Y). 2021 Feb 14;7(1):e12119. doi: 10.1002/trc2.12119. PMID: 33614892; PMCID: PMC7882534.

https://pubmed.ncbi.nlm.nih.gov/34256014/
Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, Robinson JL, Elias JE, Sonnenburg ED, Gardner CD, Sonnenburg JL. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021 Aug 5;184(16):4137-4153.e14. doi: 10.1016/j.cell.2021.06.019. Epub 2021 Jul 12. PMID: 34256014; PMCID: PMC9020749.

General Nutrients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138658/
Quan Z, Li H, Quan Z, Qing H. Appropriate Macronutrients or Mineral Elements Are Beneficial to Improve Depression and Reduce the Risk of Depression. Int J Mol Sci. 2023 Apr 12;24(8):7098. doi: 10.3390/ijms24087098. PMID: 37108261; PMCID: PMC10138658.

Specific Nutrients
Omega 3s
https://pubmed.ncbi.nlm.nih.gov/36795219/
von Schacky C, Kuipers RS, Pijl H, Muskiet FAJ, Grobbee DE. Omega-3 fatty acids in heart disease-why accurately measured levels matter. Neth Heart J. 2023 Feb 16. doi: 10.1007/s12471-023-01759-2. Epub ahead of print. PMID: 36795219.

Zinc
https://pubmed.ncbi.nlm.nih.gov/32258830/
Qu X, Yang H, Yu Z, Jia B, Qiao H, Zheng Y, Dai K. Serum zinc levels and multiple health outcomes: Implications for zinc-based biomaterials. Bioact Mater. 2020 Mar 31;5(2):410-422. doi: 10.1016/j.bioactmat.2020.03.006. PMID: 32258830; PMCID: PMC7114479.

DHEA
https://pubmed.ncbi.nlm.nih.gov/32745490/
Wang F, He Y, O Santos H, Sathian B, C Price J, Diao J. The effects of dehydroepiandrosterone (DHEA) supplementation on body composition and blood pressure: A meta-analysis of randomized clinical trials. Steroids. 2020 Nov;163:108710. doi: 10.1016/j.steroids.2020.108710. Epub 2020 Jul 31. PMID: 32745490.

https://pubmed.ncbi.nlm.nih.gov/33220453/
Hu Y, Wan P, An X, Jiang G. Impact of dehydroepiandrosterone (DHEA) supplementation on testosterone concentrations and BMI in elderly women: A meta-analysis of randomized controlled trials. Complement Ther Med. 2021 Jan;56:102620. doi: 10.1016/j.ctim.2020.102620. Epub 2020 Nov 18. PMID: 33220453.

Copper
https://pubmed.ncbi.nlm.nih.gov/21321490/
Prodan CI, Rabadi M, Vincent AS, Cowan LD. Copper supplementation improves functional activities of daily living in adults with copper deficiency. J Clin Neuromuscul Dis. 2011 Mar;12(3):122-8. doi: 10.1097/CND.0b013e3181dc34c0. PMID: 21321490.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554529/
Klevay LM. The contemporaneous epidemic of chronic, copper deficiency. J Nutr Sci. 2022 Oct 11;11:e89. doi: 10.1017/jns.2022.83. PMID: 36304823; PMCID: PMC9554529.

Pregnenolone
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200497/
Brown ES, Park J, Marx CE, Hynan LS, Gardner C, Davila D, Nakamura A, Sunderajan P, Lo A, Holmes T. A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression. Neuropsychopharmacology. 2014 Nov;39(12):2867-73. doi: 10.1038/npp.2014.138. Epub 2014 Jun 11. PMID: 24917198; PMCID: PMC4200497.

https://pubmed.ncbi.nlm.nih.gov/32119096/
Naylor JC, Kilts JD, Shampine LJ, Parke GJ, Wagner HR, Szabo ST, Smith KD, Allen TB, Telford-Marx EG, Dunn CE, Cuffe BT, O'Loughlin SH, Marx CE. Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial. JAMA Netw Open. 2020 Mar 2;3(3):e200287. doi: 10.1001/jamanetworkopen.2020.0287. PMID: 32119096; PMCID: PMC7052727.

Magnesium
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637834/
Schwalfenberg GK, Genuis SJ. The Importance of Magnesium in Clinical Healthcare. Scientifica (Cairo). 2017;2017:4179326. doi: 10.1155/2017/4179326. Epub 2017 Sep 28. PMID: 29093983; PMCID: PMC5637834.

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7/16/2018 23 Comments

Patients on the Bredesen Protocol/ReCODE

Dr. Dale Bredesen published his End of Alzheimer’s book about a year ago in the summer of 2017. The group MPI Cognition began referring patients to providers trained in the Bredesen Protocol soon thereafter.

I have begun work with close to 30 patients for either prevention or reversal of cognitive decline. I have learned many things along the way, and have streamlined my approach, introduced practices to make it more comprehensive, as well as interventions to get to the root cause of the dysfunctions that lead to cognitive decline.

There is so much to teach each patient that I have finally written a 70 page Handbook that provides much detail. It will soon be available on this website for $9.95. I will update the link when I upload it.

Here are some lessons I have learned.

THREE ASPECTS OF COGNITION
I’m not talking here about underlying causes, but about what it looks like on computer testing.
We use online computer cognitive testing to understand the pattern of people’s cognitive struggles. The program is called “CNS Vital Signs.” It is a only a 30-minute assessment and therefore cannot give us nuanced information. However, people seem to be declining in one aspect of cognition and sometimes not the others, as far as I have been able to see. It tends to be one of the following:

the speed of understanding, processing information, and responding: low scores in scales such as “motor speed,” “reaction time,”, and “psychomotor speed.”
the formation of memories: “verbal memory” (remembering words) seems to sometimes behave quite differently from “visual memory,” which is memory for going back to places you’ve previously visited, and remembering where you parked your car.
organization, focus, attention, reasoning

WHO IS AVERAGE?
Many people who come to my office to optimize cognition were previously functioning at very high levels, typically in the “above average” range. Scores in the “average” and “below average” category for them represent cognitive decline. The good thing is that they are still in a position to partner with me to understand and be motivated to follow the program. They are not dependent on their spouse or adult child.

If I’ve learned anything, it’s how much easier it is to do this work when the decline is still relatively mild.

WHAT HAPPENS ON THE PROTOCOL
The first few weeks after the initial visit, people are often overwhelmed and confused. The testing we use is complicated and unfamiliar. We have to be in contact so I can answer questions and we can move forward. Thus I have now added an hour to go over the report and recommendations from the first visit.

At the results follow up visit, we go over test results and I show people what we will address first and how. Within a few more weeks, we see changes in energy and in any chronic medical conditions.
Subsequent visits see us revisiting the basic medical issues, “deprescribing” (getting off) medications that stand in the way of health, and adopting protocol recommendations as new lifestyle habits. We also see new problems emerge and have to address those.
Most people say they are thinking better within about 2-3 months. Memory has improved: how quickly people can access words that used to escape them, or the ability to multitask, engagement with other people, sleep, headaches sometimes, digestion almost always, anxiety level sometimes, and overall energy often.

I have follow up data on only 4 patients at present. The improvements so far are very exciting and we’re not even done! I will tell each of their stories briefly in the next blog post.

THE SPEED OF NERVE IMPULSES
I worry that people with below average motor speed or reaction time will be at high risk of falls, injuries, or if they are driving, of auto accidents. One of the correlations so far has been the role of toxins. I often see high lead and mercury levels among patients seeing me for cognitive decline. I had not seen such high levels with patients who were not affected cognitively. Indeed there is research to show that lead (from the leaded paint and gasoline of the past, or from recent exposures such as working with stained glass, handling ammunition, and others) actually slows down impulse conduction speed from one end of the nerve cell to the other. Neurons talk to each other slower. Thus of course one perceives the world slower, processes inputs slower, and responds slower. When that gets much too slow, organization and memory are affected too. Literally people seem to be forgetting what they were about to do.

There is evidence that carefully removing toxic metals leads to an improvement in this process. I have not yet had the chance to verify this for myself because it takes 9 months to a year to significantly reduce heavy metals. And before I even start the process, I have to make sure a patient is healthy enough for the testing itself (testing can involve the use of a medication that chelates heavy metals, that is it goes looking for them and pulls them out, and if it finds a large quantity, we can measure it in the urine). Treatment involves removing these metals a little at a time so they never overwhelm the body’s detoxification capacity, as they would redistribute and cause further harm. It is done through a combination of sweating (infrared sauna for example) and the use of supplements, herbal remedies, and medications.

PRESENCE OF SEVERAL UNDERLYING CAUSES AT ONCE
All my cognitive decline patients have several harmful processes going on at the same time. The groups defined by Dr. Bredesen are a good framework for me, but none of my patients have had only inflammation, or only high blood sugar, or only lead or mold. My sense is that by themselves, these may cause illness, but rarely cognitive decline. For example, I would see patients with leaky gut and fatigue or joint pain, or autoimmune disease, but mentally they were as sharp as ever.

In my experience, cognitive patients have a pile-up of several impacts, and I believe they all contribute. Patients are typically inflamed: one patient has celiac disease, several had very high levels of antibodies to gluten. They typically also have excess glucose, some vitamin deficiencies, a few hormone deficiencies, and most likely either a heavy metal, mold exposure, reactivated Epstein-Barr virus, or exposure to Lyme disease. While it is conceivable that some of these impacts are not bothering them, I don’t see how I can leave any in place and just work on others. I believe that what I am seeing is that while there are many paths to becoming cognitively impaired, it isn’t actually noticeable until a critical mass of body functions are affected.

I have seen patients come from other providers who were not thorough in addressing all the pieces above. I think that is unfortunate because the longer we wait, the harder it is to reverse the damage already done. Having seen the number of different things that are wrong with each person, my concern would be that I am doing too little, not too much, from the start.

I have also seen patients come from providers who were not using the “optimal” ranges for lab values in Dr. Bredesen’s book. I don’t think we have the luxury of relaxing these ranges, quite yet. Just my 2 cents’. I also worry about the use of weak supplements, doses that are too low, or herbal shortcuts. I fear that even if they work, these leave people vulnerable to setbacks.

THE NEED TO USE FUNCTIONAL MEDICINE
The dysfunctions we uncover are all related to each other. For example, the most significant cause of high blood glucose is inflammation. The most common source of inflammation is increased intestinal permeability (leaky gut). Patients with excessive intestinal permeability cannot efficiently detox heavy metals, and other toxins. Heavy metals of course cause high blood glucose, and inflammation. So the patients are running several sets of interlocking vicious cycles, and the work we do is to extricate them systematically from these situations. Thankfully, functional medicine offers guidance for this. None of these links are commonly recognized or addressed in conventional medicine. I don’t believe I could do this work without an excellent foundation in functional medicine.

In addition to interlocking vicious cycles, patients are also on medications that lock in their dysfunctions. For example, many have heartburn and take proton pump inhibitors, which worsen the absorption of a number of nutrients. The first job is to heal the underlying cause of the heartburn. This has to happen as we replenish the most critical nutrients and reverse inflammation. Again, the functional medicine tools allow me to move forward. Before I studied functional medicine, I used to have patients on chronic proton pump inhibitors that simply could not get well. I did not know how to guide them to digestive wellness.

MAKING AND KEEPING PEOPLE WELL
We have to find alternatives to conventional medical treatment that work just as well if not better. For example, it won’t do to put patients on non-steroidal anti-inflammatory drugs (NSAIDs), on acid blockers, on anti-anxiety medications, on medications for sleep, on statins (they worsen glucose regulation, harm mitochondria, and interfere with myelin synthesis), on antibiotics (unless there is a life-threatening situation), and more. But we can’t leave people untreated for any of the conditions for which these would normally be prescribed. Again, functional medicine comes to the rescue: these conditions have diet and lifestyle solutions.

We have to keep patients safe while they are focusing on reversing their cognitive decline. Fractures, surgeries, illnesses, stressful life events, new mold or Lyme exposure, and ongoing environmental toxin exposures, all must be avoided if at all possible, or their impact must be reduced. It becomes necessary to discuss how to avoid household toxicants, how to avoid getting colds, how to better address a conflict with another person (all that is in the e-book), and more.

At the same time, our interventions must be safe. Many patients need to start a ketogenic diet, because ketones are a better source of energy for the brain in decline. But the ketogenic diet clearly poses major challenges. Excessive weight loss, loss of enjoyment, friction with family and friends, and loss of social contact due to not being able to enjoy some of the previously enjoyed foods - all these can be harmful.

We need to proceed efficiently, cautiously, quickly, be comprehensive, incredibly organized, forgiving, optimistic, strategic, and compassionate. I won’t lie, it is a challenging field!

CONCLUSION
I’m in awe, every day, of the dedication and sense of agency of my patients. I hope that everyone at least learns about this protocol so they can take immediate action when they suspect the start of cognitive decline. We should remove the stigma of impaired cognition, so we can address the topic with each other and support each other in making lifestyle changes. I believe this is what we all have to do to create the end of Alzheimer’s.

23 Comments

12/22/2017 52 Comments

Group Programs to Reverse/Prevent Cognitive Decline

Since training with Dr. Dale Bredesen, and since the publication of his book, I have seen more than a dozen patients wanting to focus on cognition. It is not an easy program, but patients are feeling better in a variety of ways, and some are starting to feel cognitively sharper as well. It is a long program, and there are many aspects to look at - after fixing the nutrient deficiencies and the hormone imbalances, many people need more work on heavy metals, mold and chronic infections.

TWO PROGRAMS
I am launching a group version to try to lower costs for people who are having fairly mild symptoms. There are two programs.

PLEASE NOTE!!

If you are in danger of losing your work or other important part of your life, please seek out a practitioner as soon as you can. The list of practitioners is available from MPI Cognition, as well as on the Institute for Functional Medicine web page (you have to look up individual practitioners in your area).
If you have serious medical issues (insulin-treated diabetes, recurrent hospitalizations, severe illness from exposure to mold) you will not want to wait to follow a treatment plan online. By necessity, the online course will be slower and less well-targeted to your needs than any work with a good local practitioner.
If you have the funds available, the online course will not be better than a local practitioner.

FOR LOCAL RESIDENTS
For California residents who live locally here in the San Francisco Bay Area, and are willing to drive to my office, I am offering a two-part program consisting of the following:

1. An initial day long class that will involve detailed discussion of the protocol, individual visits with me, individual cognitive testing using CNS Vital Signs, and ordering of lab testing appropriate for each person's situation. Access to high quality affordable supplements will be offered.

2. A second day about 2 months later, to go over the lab results as a group and explain what to do for each one, answer questions, and finish explaining details of the protocol. More supplements are often used at this stage.

The cost of this program is $1200-1400 per participant, provided we can put together enough participants. I will ask patients to fill out questionnaires ahead of time, and I will spend 20 minutes with each person and give you requisitions for labwork and supplements at reduced prices, optimizing costs.

FOR PEOPLE WHO ARE NOT LOCAL
For patients who live too far to attend a local course, I am offering an online course with monthly group video calls for 1 year. That will take people step-by-step through the entire Bredesen protocol. In this case, patients will have to use their local providers or other methods to get lab testing ordered, as I cannot order testing for patients who are out of state. Also, while this may help a person diagnose a problem, like leaky gut or mold illness, these diagnoses don't always resolve well with self-treatment and may require a local provider in addition to the online course.

FOR PEOPLE WHO ALREADY HAVE A BREDESEN-TRAINED PROVIDER
The online course may be helpful in supporting anyone who is already doing the Bredesen protocol with their local provider.

I will go over this online program in more detail in a free video broadcast January 10 at 5 PM Pacific time. The link to this video is here. There will be no video playing in this spot until the date of the video, but then if you have missed that time you can watch the video at the same link anytime after January 10.

The online course costs $500 per participant, assuming we can enroll enough participants.

CONTACT US
There is much interest, and we are starting small. Please leave your email address here to a newsletter list that will focus only on group programs to reverse/prevent cognitive decline.

52 Comments

9/21/2017 12 Comments

Awakening from Alzheimers

Today is the first day of a series of videos about preventing and reversing cognitive decline. The website is here:
http://event.awakeningfromalzheimers.com/

Today's episode was a start, briefly discussed the importance of reviewing a person's medications to make sure there isn't a combination that might worsen cognition, and the importance of optimizing blood sugar and sleep. I believe this is going to be worthwhile, and easy to watch. There are many episodes, and it will be an investment, but so far, it looks informative.

12 Comments

9/5/2017 353 Comments

The End of Alzheimer’s by Dr. Dale Bredesen: A Book Review

In November 2014, neurologist Dale Bredesen M.D., published the first article on reversing cognitive decline. Using a combination of approaches centered on lifestyle and supplements, 9 out of a total of 10 patients reversed their dementia, and 6 of them even went back to work (1).

I was very excited when I read that article, especially because Dr. Bredesen’s approach fits so well within a functional medicine framework. I couldn’t wait to put it into practice and wrote a blog post about it (some-approaches-can-reverse-cognitive-decline.html).

Since then, I have taken Dr. Bredesen’s 3-day training for health care providers who want to apply the Bredesen protocol (now called “ReCODE”, for “reversal of cognitive decline”). I have also been seeing several patients for a few months and noticing some encouraging early results. A few patients are just starting to receive results of blood tests that will help us focus our efforts at reversal.

In August 2017, Dr. Bredesen published his book “The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline.” The book promptly sold out on Amazon but should be in stock again in early September. It is also available as a Kindle version, which is what I got. Though I had already spent many hours studying this information and organizing it to make it usable, I still found the book highly valuable. I also read it with an eye to considering whether it might be possible for many people to implement ReCODE on their own.

WHAT YOU NEED TO DO
What is the ReCODE approach? Basically you put into place universally beneficial habits (sleep, exercise, diet, stress reduction), and add supplements, alongside repairing dysfunctional processes (digestion, hormone function, processing of toxins) to the point that a number of blood test values are “optimized.” The ranges used by conventional labs are not sufficient here – we are looking to reverse illness so everything has to be “optimized.” And then you add supplements and herbs which in sufficient doses are known to enhance cognitive function. As you will see, the devil is in the details, but if you understand cognitive decline, it’s obvious that this would be the way to go.

“The End of Alzheimer’s” starts by reviewing the current beliefs about dementia – as summarized, for example, on the web page of the Alzheimer's Association – stating that basically, Alzheimer’s Disease is considered incurable and lacks effective medications to manage its symptoms. A search for “Bredesen” on the Association’s website turns up some references to grants from a decade ago, focusing on basic research rather than clinical research. I could not find the 2014 article mentioned above, and the subsequent clinical articles authored by Bredesen (2), (3).

One chapter of Bredesen’s book focuses on how a dementia patient feels. I loved this analysis: until now, people were not able to report on how things felt while they were in the throes of this disease because they never regained enough clarity to make the comparison. There’s nothing more compelling, once you have recovered a function, than to look back and remember how things were when you had lost it. For example, “Eleanor” recounts:

“Before I reversed, it felt like I had a filmlike gauze over my brain that kept me from really connecting with others and from being able to easily engage in normal conversational back-and-forths. […] I couldn’t have told anyone that all these things were problems last year. I couldn’t put it all together.”

I found this section deeply moving: this is why my colleagues and I are in practice, to make an impact as meaningful as returning a person to their life, their work, and their connections with loved ones. Witnessing that never gets old!

WHAT NOT TO DO
Another chapter outlines what most people do wrong that causes them to get ill, and much of it applies to Alzheimer’s, other dementias, and other conditions that involve inflammation (which is most other chronic conditions, from depression, to autoimmune disease, to joint and muscle pains and digestive issues). It's a funny chapter, and also poignant, because it describes the way we functional physicians go through life – seeing hidden dangers where there was previously routine: the morning mocha and danish pastry, tuna sandwiches, diet sodas, afternoon candy, pasta dinners, and mildewy basements. I have to admit, those were almost daily “exposures” for me for decades. Dr. Bredesen writes:

“The bad news is that the more you see yourself in the lifestyle I described, the more certain you can be that it is already impairing your mental sharpness.”

Actually, I would say, that is the good news. I know firsthand how good it feels to improve your lifestyle even partially. Many people come for a consultation because they are in pain and fatigued, and also concentrating poorly and feeling apathetic. They are not yet demented and there are many steps we can take to prevent that from happening. But their early on-course indicator and source of motivation is that they soon begin to feel better in a variety of ways. It doesn’t always require a complete life transformation. Our bodies can be quite forgiving, and having witnessed this repeatedly, I have no trouble believing that we can reverse dementia.

A theme throughout the book is the near universal negative reaction of respected neurologists and people’s primary care physicians. It seems hard to believe that medicine would be so rigid, but at the same time, that is not entirely a bad thing. It would be a problem if we adopted new treatments without giving them much thought or study. However, from the point of view of functional medicine, a ReCODE type approach is completely in keeping with what we normally do successfully in pursuit of reversing other illnesses. The skepticism toward ReCODE is the same as that regarding reversing type 2 diabetes, or hypertension, or arthritis. Most people’s primary care and specialist physicians are very critical and remain in disbelief. Strikingly, they do not reach out to us to investigate, as though they were not interested. But I believe instead that they simply don’t trust themselves to figure out if something is really working: they would rather wait for an official guideline. The problem with dementia, as with many of the other “incurable” illnesses patients face, is that patients don’t have years to wait, and may even have lost faith in a system swayed by big business interests.

THE SCIENCE BEHIND THE BOOK
Part 2 of the book delves into the science that explains how dementia comes about, and thus how these problems can be tackled and reversed. The science is very well laid out, with useful metaphors – some of which I immediately adopted with my “cognitive decline” patients. I find that knowing how something works improves my motivation to implement a complicated program. Dr. Bredesen compares cognitive decline to the “roof with 36 holes:” it’s raining in your house because the roof has many defects – not just a few. If you fix just two or three, it will continue to rain in your house. Another way I understand it is the problem of “feed-forward cycles” – to interrupt a negative feedback loop, you just need to stop one event from happening. But in a system of interconnected feed-forward cycles, you have to stop most of the links.

So ReCODE is very much the inevitable conclusion of Dr. Bredesen's years of basic research. The novelty here is not the belief that mercury, or mold, or B vitamin deficiencies, or lack of thyroid hormone, can cause dementia. These are well-established medical facts. The novelty is in demonstrating that even small alterations in these parameters (being in the “normal,” but not the “optimal” range) can add up and create devastating decline. Reductionist clinical experiments, where only a single parameter is changed, will often have negative results where a combination of changes would have succeeded. But that, again, is functional medicine, and Dr. Bredesen admits that he was influenced by his wife Aida, an integrative physician. It is Dr. Sid Baker’s old metaphor: if you’re sitting on three thumb tacks, removing one will not make you feel better. The argument from the conventional medicine side is that big enough studies will include enough patients who are lacking only one aspect to get picked up in the statistics. Unfortunately this is not how Alzheimer’s disease develops: you often need more than one impairment to develop it, and reversing it requires you fix them all – thus very few people get better when you address only one of their impairments.

In the book, you will learn about three major types of Alzheimer’s disease, as well as type 1.5, which combines type 1 and type 2. These three types are the ones most easily reversed. Now you begin to have a framework for the tasks that lie ahead, but it will require first figuring out what type you have, and this means laboratory testing.

NUTS AND BOLTS
There is no reason your primary care provider cannot order all the laboratory tests suggested in the book and use Dr. Bredesen’s optimal ranges to pinpoint sources of problems. There is a skill set that comes with fixing some of these deficiencies, but it is certainly a good first step to identify them. Insurance sometimes pays for this, and flexible spending accounts may cover the supplements that help address some of the problems found. But your physician will likely not order and interpret lab tests simply based on a book, because as I mentioned earlier, they are most likely waiting for an official recommendation from the American Board of Internal Medicine, Board of Family Physicians, or equivalent neurology association. And the expert panels are not yet convinced.

So, the question arises as to how realistic it is to think that many people would navigate this protocol on their own. It is a complex endeavor in the face of an emotionally charged situation. Nonetheless, some patients have done so, and I can’t think of any other way to bring about change than to empower patients to feel hopeful, and to pressure their physicians and insurance companies politely and persistently until more get on board.

By combining several direct-to-consumer sources like 23andme and DirectLabs or RequestATest, one can make some headway, assuming hormone status is optimal. If hormone therapy is needed, a physician's prescription for thyroid hormone, for estrogens, for progesterone, and/or testosterone will be required, and any physician would first have to be convinced that they are needed and safe.

The services of a Bredesen-trained health care provider can be expensive, so I would love to see a calculation of how much money patients save when we use tricks we know for less expensive lab tests, specific supplements. We also use our experience and expertise to avoid going down wrong paths. If anyone has already calculated the cost of getting these labs without a physician, please leave a comment.

I used a random few labs to get a quick sense:

TEST IN MY PRACTICE   IF PATIENT ORDERS
total T3 $0-4 Direct Labs: $49
free and total testosterone   $0-15 Direct Labs $79
Hemoglobin A1C $0-4 Direct Labs $119
Homocysteine $0-4 Direct Labs $69
ApoE4 genetic test $1-50 $199 for 23andme

I believe you will spend a lot more ordering labs on your own than through a savvy functional medicine provider, perhaps in the order of $2000 more. Also, you will not be able to get all of them: I could not find the innate immune labs required for a diagnosis of mold impact on Direct Labs.

I imagine that Dr. Bredesen could not write a book where he tells people to go see a functional medicine physician (though he does provide a link in Addendum A). And the truth is I am hopelessly biased, as seeing individual patients is in fact how I make my living. But do take a look for yourself, and make your own decision.

Some of the tests mentioned do require a physician who knows enough integrative medicine to know of (and believe in) testing using Cyrex Labs, interpret integrative stool testing, prescribe the chelator for the urine heavy metal testing, etc. You may need a provider who knows how to take patients off proton pump inhibitors, how to control blood sugar and reverse prediabetes, how to use a low carb/high fat diet safely, treat for mold illness (CIRS – chronic inflammatory response syndrome), Lyme disease and co-infections, and mercury overload.

Those of us who practice functional medicine have had to learn each of the above since our graduation from medical school, as well as keep up with advances as would be required of any physician. The 25 annual hours that are mandated in order to keep our licenses fall far short — this is why we can’t accept insurance rates of reimbursement that are based on a model where a physician sees 20 patients a day.

HOW TO PROCEED
I believe that any hope of making ReCODE more affordable might lie in setting up group visits. Especially at first, it could be much more cost-effective to go through the evaluation and intervention with a group of patients and their caregivers. This will require that enough patients reach out to us to start setting up these groups. Some of my colleagues dream of a ReCODE “center,” where patients could go and attend a series of classes, be seen by physicians in a cost-efficient manner, and quickly be on their way to improving cognition.

“The End of Alzheimer’s” goes on to discuss the steps necessary to follow the protocol in great detail, and some common problems faced by those who have. In person, Dr. Bredesen is positive, encouraging, hopeful. He has witnessed miracles after a professional lifetime of seeing drug treatments fail. He has worked all his life to understand this disease, and the solution to the problem turns out to be a complicated one. As in other endeavors in life, it’s of little use to wish for what is not true to become true. Instead, we ought to “turn around and face in the direction the horse is going.”(4) This is one disease that cannot be solved by a single cutting edge pharmaceutical agent, not in 2017, but you don’t have to just decline and suffer. Commit to the  ReCODE protocol for 6 months, and then decide if what you lose in implementing ReCODE is worth the bargain of saving your brain.

ONLINE APPROACH
I have put together a video outlining how I plan to structure an online course to take patients through a protocol to reverse/prevent cognitive decline structured on Dr. Bredesen's approach.

REFERENCES

(1) Aging 2014 Sep;6(9):707-17.
Reversal of cognitive decline: a novel therapeutic program
Bredesen DE

(2) Aging 2016 Jun;8(6):1250-8
Reversal of cognitive decline in Alzheimer's disease.
Bredesen DE, Amos EC, Canick J, Ackerley M, Raji C, Fiala M, Ahdidan J.

(3) Aging 2016 Feb;8(2):304-13.
I nhalational Alzheimer's disease: an unrecognized - and treatable - epidemic.
Bredesen DE

(4) The Five Things We Cannot Change, David Richo, 2006

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