Category: chapter 21

21. FISETIN, A SUPPLEMENT THAT MIGHT ADD YEARS TO YOUR LIFE

Colonial Tovar in Venezuela

Summary An exciting supplement showing a lot of potential is Fisetin. Animal studies suggest that taking Fisetin can add 10% to the lifespan and improve health quality. It is not clear yet whether these positive results will translate to humans. Still, since Fisetin does not show side effects, I decided to take it. I am in good company as the well-known longevity expert Dr. Sinclair began taking 500 mg of Fisetin daily a few years ago. The Mayo Clinic is conducting research on the impact of Fisetin on humans.

1. What is Fisetin?

Fisetin is a flavonoid found in many fruits and vegetables. It is mostly in strawberries. It is also in apples, persimmons, grapes, onions, and cucumbers. For those who love strawberries: 37 strawberries are equivalent to what is considered an impactful intake of Fisetin.

What is a flavonoid? Flavonoids are compounds present in many plants, fruits, vegetables, and leaves, with potential medicinal applications. Some refer to them as “vitamin P” (polyphenols or bioflavonoids). Plants use flavonoids for their own growth. They help plants attract pollinators and fight infections. They also give some fruits and vegetables their deep, rich colors.

2. Positive Health Effects of Fisetin

Various cellular and animal studies demonstrate Fisetin’s range of positive health effects. It acts as an (1) antioxidant and (2) senolytic, which is an agent that induces cell death in senescent or unhealthy cells. It also serves as a (3) neuroprotective and memory-enhancing agent. Additionally, it has the ability to mimic calorie restriction.

3. Fisetin Imitates Calorie Restriction

Calorie restriction is widely accepted among the scientific community. Consuming 10 – 40% fewer calories can lead to improved health and longevity.

How? It utilizes various mechanisms, also called “pathways”: (1) It activates sirtuins, which are proteins involved in cellular health. (2) It promotes autophagy as a form of cellular housekeeping that removes “zombie” cells. (3) It increases AMPK activity, an enzyme involved in cellular metabolism.

Research strongly suggests that Fisetin elicits a similar response to calorie restriction, initiating these three pathways as well. The activity of these pathways declines with age. However, mouse models show that Fisetin can boost their activity. This boost keeps the cells youthful.

4. Fisetin as a Senolytic (a compound that eradicates senescent cells)

Senescent cells are old cells with damaged DNA that have lost their ability to divide and contribute to aging. Also known as “zombie cells,” senescent cells do not die; they accumulate and inflame surrounding cells and tissues. Cellular senescence gradually weakens an organism by making it more susceptible to age-related diseases. A study published in the journal Aging showed that Fisetin eliminated about 70% of senescent cells. It did no harm to healthy, normal human cells. To me, this seems like a great result.

5. Fisetin’s Role as an Antioxidant

Oxidative stress, another contributor to the aging process, develops from an imbalance between free radicals and antioxidants in the body. Free radicals potentially damage cells, proteins, and DNA, while antioxidants help neutralize and minimize their harmful effects. Fisetin works as an antioxidant by protecting cells from free radical damage. It also exhibits anti-inflammatory properties by turning off pathways that promote inflammation and decreasing the production of inflammatory compounds. 

Glutathione, a powerful antioxidant, helps protect our cells from oxidative stress and wards off aging-related diseases. As we age, our supply of glutathione declines. But maintaining adequate glutathione levels is crucial. Low levels are linked to a higher incidence of cancer, diabetes, and heart disease. Research indicates that Fisetin may help preserve the body’s supply of glutathione.

6. What Dosage of Fisetin?

There is no definitive answer to this. Some, like Dr. Sinclair, take 500 mg daily with yogurt. Others, like the Mayo Clinic, have a protocol of 20 mg/kg/day for 2 days. They repeat it once after 1 week and then once after 1 month. This “hit and run” protocol is cheaper than taking 500 mg per day, as Fisetin is quite expensive. Clear that the correct dosage is a topic to follow.

7. Safety

The “no-harm” approach is central to my decision to use any supplement. I take several supplements based on “hope” when there are credible indications that they might provide certain benefits. 

However, I only take supplements considered completely safe and that do not interact with any medication. This seems to be the case with Fisetin, as far as I could find out. It’s important to note that what holds in animal models doesn’t always directly translate to humans. This is due to differences in physiology and dosage responses. Therefore, more research is crucial to validate these effects in humans.

8. Weak Points of Supplements

Supplements generally have two weak points:

1. Their production is not officially regulated or controlled by health agencies, so it’s crucial to buy from reputable companies.

2. Many health claims are not scientifically proven.

9. Where Do Supplements Rank in Relation to a Longer and Healthier Life?

Nutrition, exercise, sleep, stress management, and social life are five key elements. These elements, if managed well, contribute to a healthier and longer life. Fortunately, expert recommendations across these categories often align. However, food and exercise can sometimes lead to debates and differing opinions.

Discussions on food and exercise are mild compared to the sixth category: supplements! Supplements are often controversial, with many unproven health claims and contradictory expert opinions. Yet, this is also the most exciting category because we are continually discovering the potential of new supplements.

Take care and live a happy and healthy life,

Robert

21. BERBERINE, A TRULY GREAT SUPPLEMENT (health project99+)

The city of Hoorn in The Netherlands

Summary One of my favorite supplements is Berberine. It has similar positive effects on blood sugar levels as the prescription drug Metformin, but without its side effects. However, I do not take Berberine for its blood sugar management and its other potential benefits. Berberine interests me mainly because it may play a role in slowing aging and extending life expectancy with years. Interesting research is ongoing (see point 9 of this blog).

Berberine is an herb extracted from several different plants, specifically shrubs called Berberis. Berberine originates from an ancient Chinese herb called Coptis Chinensis French. 

1. Six Categories for a Longer and Healthier Life

Nutrition, exercise, sleep, stress management, and social life are five key elements. These elements, if well managed, contribute to a healthier and longer life. Fortunately, expert recommendations across these categories often align. However, food and exercise can sometimes lead to debates and differing opinions.

Discussions on food and exercise are mild compared to the sixth category: supplements! Supplements are often controversial, with many unproven health claims and contradictory expert opinions. Yet, this is also the most exciting category because we are continually discovering the potential of new supplements.

We live in the age of AI. I am convinced, or at least hopeful, that AI will spur an exponential growth of new medicines, that it will also lead to the development of many new supplements and new ways to proof their effectiveness.

2. Weak Points of Supplements

Supplements generally have two weak points:

1. Their production is not officially regulated and controlled by health agencies, so it’s crucial to buy from reputable companies.

2. Many health claims are not scientifically proven.

3. The Importance of Remaining Critical

I try to remain critical. Take Resveratrol, for example. Fifteen years ago, it was heralded as a miracle supplement. Later, it turned out to be a false alarm. Its half-life is only about 1 hour. This makes any positive effects very short-lived. I took Resveratrol for a few years until I discovered this fact, and I consider it a waste of money.

4. Berberine (proven claims)

Berberine has been scientifically proven to lower blood sugar as effectively as Metformin. It helps in weight loss. It also improves heart health. individual users as Berberine.

I have been taking Berberine for a few years now. It offers similar benefits as the officially approved medicine Metformin. However, I stopped taking Metformin. I experienced side effects, such as bloating, nausea, and stomach cramps.

A combination of Berberine and metformin can enhance the effects of these two medications. Research has shown their combination can improve blood sugar control. Also, Berberine can make it easier to tolerate metformin with fewer metformin side effects. Therefore, if your doctor says it is okay to take both Berberine-metformin, you can go ahead and do so.

On YouTube, the comments sections of videos where doctors discuss Berberine are quite interesting. Generally, the comments are positive, and many emphasize the absence of side effects. Among the supplements I follow, few receive as many positive reviews from users as Berberine does.

5. Claims (Not proven but with interesting indications from several trials)

Berberine may reduce inflammation in various ways, suggesting it could be used to treat inflammatory conditions like arthritis. It may also offer additional benefits. It could potentially aid in treating conditions such as depression and nonalcoholic fatty liver disease. Some studies suggest it might even help reverse arterial plaque (if true this would be a true miracle) and address hormonal issues. All interesting, but not proven.

6. Safety

The “no-harm” approach is central for me when deciding to take any supplement. I take several supplements based on the hope and indicating they might provide certain benefits. However, I only take supplements considered completely safe and that do not interact with any medication.

7. Half-life time of Berberine

Berberine has a half-life of several hours. This characteristic makes it ideal to take at a dosage of 500 mg twice daily. It’s best taken with meals.

8. How long does it take for Berberine to lower A1C (that indicates your blood sugar level)

Most studies have examined Berberine’s effects over 90 days. We can assume that noticeable effects likely take about three months. In contrast, Metformin works much faster, typically yielding full benefits within 4-5 days. However, the overall impact is similar between the two.

9. A bit more on life extension potential of Berberine

Metformin (and Berberine) are believed to mimic some biological effects of caloric restriction. This is a well-studied method for potentially increasing lifespan. In animal models, Metformin-treated mice often showed signs of improved health span. They lived healthier lives with fewer age-related diseases. These improvements include better metabolic health markers and reduced instances of age-related conditions.

It’s important to note that what holds in animal models doesn’t always directly translate to humans. This is due to differences in physiology and dosage responses. Therefore, more research is crucial to validate these effects in humans. The TAME (Targeting Aging with Metformin) study is a significant clinical trial aiming to assess Metformin’s effects on aging-related diseases. It is anticipated that the results for Metformin will be comparable to those for Berberine.

Enjoy a happy, healthy and long life,

Robert, your health friend,

21. OMEGA-3 SUPPLEMENTS, OFTEN NO NEED TO TAKE THEM (health project99+)

Somewhere in the East of Venezuela

Summary: 1. Omega-3 fatty acids are important for your health; all your cells use them. 2. Most people are deficient, but the solution is easy for most (change of diet, not taking supplements). 3. Taking high amounts of Omega-3 fatty acids is recommended by many on internet, but this is something you really should check with your doctor. 4. Many supplements are of low quality and can work counterproductive. 5. Higher amounts of Omega-3 fatty acids can have unexpected health consequences like atrial fibrillation.

Your body needs the different Omega-3 fatty acids, especially the EPA, DHA and ALA types. They are essential for a broad range of health benefits. These benefits start with the heart and brain and extend to a healthy cellular structure and function. All your cells use them on a constant basis.

The good news is that you get enough if your diet includes fatty fish twice per week (herring, salmon etc) for the EPA and DHA. For the ALA flax seed or a handful of walnuts daily should be sufficient. The half-life ( = time a compound stays active in your body) of EPA and DHA is approximately 3-4 days. This is excellent. It explains why a few helpings of fatty fish per week give you sufficient Omega-3. This is as suggested by health authorities.

So do you need to take supplements? They are among the most promoted and sold supplements by the industry. However, just like vitamin C, they are easy enough to get through a balanced diet. Really think twice and look at your diet before you decide to take a supplement.

If you do not like fish or are allergic to nuts, supplements might be necessary. I say this with some caution. Omega-3s supplements can be of bad quality, and they often are. They might even cause unwanted effects like triggering attacks of heart rhythm issues. These issues include atrial fibrillation, which has happened to me. 

In blogs like these it is standard practice to refer the reader to his/her doctor. This is often done as part of one’s “cover your ass” policy. However, in the case of Omega-3, it is advisable to do so. Of course, we hope that your doctor is open-minded. We hope they look at supplements and other alternatives in a welcoming way. Which is not always guaranteed.

The Omega-3 index

Experts typically recommend targeting an Omega-3 index between 8% and 12%. Most Americans have on average 4%, much too low and up to 80% are below the 8%. The Omega 3 index is a blood test. It measures the amount of EPA and DHA found in the membranes of red blood cells. A test above 8% is desirable. The solution of course is not taking a supplement, but to improve one’s diet.

Recommended Intake of Omega-3 fatty acids

Various health organizations suggest around 250 to 500 mg combined EPA and DHA per day for adults. This supports heart health. Of course there are differences between children, men, women, patients etc. The figures I use are rough estimates only.

There is no established upper limit for EPA and DHA from dietary sources. However, supplementation guidelines often recommend not exceeding 3,000 mg (3 g) per day. This is to avoid potential side effects. Some go to 5,000 mg (5 g) per day.

Discuss with your doctor what “excessive” means in your case. Taking up to 5000 milligrams per day is considered safe for most people. However, it is definitely not safe for everyone. If you are like me and are susceptible to atrial fibrillation, more than 1000 mg of combined EPA and DHA per day might already be too much.

For ALA there isn’t a specific recommendation. However, on internet I see the following suggestion: 1,600 milligrams per day for adult men. For adult women, it is 1,100 milligrams per day.

Why take more?

Why should you take more than the recommended least quantities? There is a lot of interesting research going on that indicate (not proven!) that higher amounts of Omega-3 fatty acids can contribute to a longer and more healthy life.

One example from reliable internet sources

According to new research Omega 3 and Vitamins D and exercise slows biological aging by several months. Older adults who took 1 gram of polyunsaturated omega-3 fatty acids from algae slowed biological aging. They mixed it with vitamin D (2,000 international units per day) and 30 minutes of exercise three times a week. This combination slowed biological aging by approximately 2.9 to 3.8 months over 3 years.

While omega-3 alone reduced biological age, the combination of all three interventions had an even greater impact. A reduction of a few months in biological aging may seem modest. However, this could have meaningful public health benefits. These include a lower prevalence of certain age-related conditions.

Further research has also suggested that a combination of omega-3, vitamin D, and exercise may lower the risk of cancer.

But as always, approach these conclusions with caution as further research is needed. Very few claims are 100% scientifically proven. 

What I saw on internet are interesting discussions, a lot of promises, but little proven. Treatments are accepted to slow down aging at the molecular level. However, there is no 100% proof that this leads to a longer life. Similarly, there is no guarantee of better health. Still, many hopeful signs.

If you take Omega-3 supplements

Omega-3 supplements are best consumed with meals, particularly meals containing dietary fats, as this enhances absorption.

Check which brands are reputable. Many are not and the supplements they sell are often oxidized and can be damaging to your health. Preferably buy fish oil, not in capsules, in a dark bottle. Store the oil (or capsules) in the fridge, especially when open. You can do that only for 4 weeks. Fish oil is rich in omega-3 fatty acids, which can easily oxidize in heat, light and air

Oil tends to be absorbed better but can be very expensive. You rely on your digestive system to effectively break down the capsule before it can absorb the omega-3. Most brands use pork or beef gelatin, which is very tough and thus harder to break down.

Best sources for Omega-3s fatty acids.

Natural sources should suffice. For EPA and DHA especially cold water fish like herring and wild salmon. Also eggs can contribute. For ALA flax seed, chia seeds, walnuts.

As I said, it is important to know what was the food of the herring or salmon you eat. The nutrition of farmed salmon is very different from the food of wild salmon. As a result, it has much less EPA and DHA.

The same applies to eggs. Eggs from pasture-raised chickens contain 120 mg of DHA and 23 mg of EPA per large egg. This is more than six times the amount provided by the eggs of grain-fed chickens.

For herring (Atlantic), a 100-gram serving typically contains approximately 770 mg of EPA and 1,000 mg of DHA. For salmon (Atlantic, farmed), a 100-gram serving usually provides around 400-700 mg of EPA and around 700-1,000 mg of DHA.

All easy to calculate. Consuming 300 grams of fatty fish per week provides approximately 5,000 milligrams of EPA/DHA. This amount easily puts you above the minimum needed, which is approximately 2,000 to 3,500 milligrams for the week. Add a few eggs and one can be sure not to be Omega-3 deficient.

Half-life

I already mentioned the long biological half-life of EPA and DHA. This means the time it takes for half of a substance to be eliminated from the body. 

For EPA the half-life is estimated to be around 37 to 82 hours. Half-life of DHA is much longer ranging approximately from 72 to 144 hours.

Often you read about a preferred ratio of EPA and DHA of 2:1. Achieving this ratio is difficult, especially if you rely on natural sources only. However, it is more important to ensure adequate overall intake of both omega-3 fatty acids. This is more crucial than focusing on the precise ratio of EPA to DHA. The half-life of ALA is not known.

Bio-availability

The bio-availability of nutrients refers to the extent and rate at which they are absorbed and utilized in the body. For EPA and DHA Omega-3 fatty acids EPA and DHA the natural sources tend to have very high bio-availability. When consumed as part of whole foods, they are present in the form of triglycerides, which are well absorbed. (note: Triglycerides are a type of fat (lipid) found in your blood).

Potential Risks of Excessive Intake

Bleeding Risk: Doses at the high end of omega-3 fatty acids (over 3,000 mg per day) can increase bleeding risk. This is because of their blood-thinning effects. This is especially important for individuals taking anticoagulant medications. Like many people I take these.

Immune Function: Some studies suggest that very high doses of EPA and DHA might suppress the immune system. However, this is not typically reached through diet or normal supplementation. A dysfunctional immune response can lead to a viral or bacterial infection.

Gastrointestinal Effects: Not surprisingly excessive amounts may lead to gastrointestinal discomfort, such as diarrhea, indigestion, or fishy aftertaste. This is the case with many supplements.

Vitamin E and Oxidative Stress: High doses of fish oil may increase oxidation levels. This effect is because of EPA/DHA. This can deplete vitamin E. Some supplements include vitamin E to counteract this.

Pregnancy and Breastfeeding: Pregnant or breastfeeding women should be cautious with fish oil supplements to avoid excessive intake. They should also aim to meet recommended levels for fetal and infant development.

Interactions with Medications: Those on blood thinners, aspirin, or high-dose anti-inflammatory drugs should consult with a healthcare provider. Omega-3 can exacerbate their effects.

What is the use of EPA, DHA and ALA?

EPA (Eicosapentaenoic Acid) plays a crucial role in reducing inflammation and is involved in the production of signaling molecules called eicosanoids, which have various important effects on cardiovascular health and immune system regulation.

DHA (Docosahexaenoic Acid)  is a vital structural component of cell membranes, particularly in the brain, eyes, and nervous system, where it supports cognitive function, vision, and overall neural development.

ALA (Alpha-Linolenic Acid) serves as a precursor to EPA and DHA, providing an essential source of omega-3s in plant-based diets, and is involved in energy metabolism and various physiological processes, although its conversion to EPA and DHA in the body is relatively inefficient.

This is it. A long one, but it helped me a lot.

Enjoy a happy and healthy life and stay critical!

Robert, your health friend

When I still had to wear ties

21. GLUCOSAMINE: A SUPPLEMENT FOR YOUR JOINTS (health project99+)

1: Supplements are just one aspect of pursuing a longer and healthier life. 2: The internet is flooded with many supplements and incredible claims, so it’s important to be wary of these, also when written by me:). Often, when something seems too good to be true, it likely is. I know no one ever does it. However, you might wish to consult your doctor and ask for example about possible interactions with medicines you use.

I personally use over ten supplements daily. Some, like Glucosamine, because they work well for me, even if not fully backed by research, although I would prefer that of course. There’s also a category of “hope” supplements, supported by ongoing research and developments in AI. I take these “hope” supplements only after ensuring they do no harm to my body. In worst case scenario only to my wallet.

My goal as always is to write this all down for my own benefit. And share my insight and experience (for what it is worth) with you.

1. Glucosamine and Osteoarthritis/painful joints

Glucosamine is widely used to alleviate “osteoarthritis,” also known as “degenerative joint disease” or “wear-and-tear arthritis.” This condition involves the gradual deterioration of cartilage in the joints. Cartilage? That is the flexible connective tissue found in joints and other parts of the body. It provides the smooth, slippery surface for motion, reducing friction and absorbing shock. Great if it works, painful if it does not. When you age this connective tissue erodes and cause your joints to hurt when you move. Unfortunately I know all about this.

Many people over 60, and a growing number of younger individuals, suffer from joint problems. This is due in part to factors like joint injuries, genetic predisposition, and….increasingly obesity. It’s predicted that by 2050, over 50% of Americans will be obese. Osteoarthritis commonly affects the knees, hips, hands, and spine, causing pain, stiffness, and reduced mobility.

2. What is Glucosamine?

Glucosamine is a naturally occurring compound in human cartilage and is often used as a dietary supplement for joint health. It plays a crucial role in building and maintaining cartilage.

It’s important to note that the body’s endogenous production of Glucosamine is a complex process. Levels may fluctuate based on various factors. These include age, health status, and physical activity levels.

To understand how much naturally occurs in the body, extensive biochemical analysis is required. This analysis is more detailed than what is typically done outside of research settings. It is clear however that many people do not produce enough Glucosamine. For those, supplements might be useful.

3. My own experience in taking Glucosamine (=very positive)

The effectiveness of Glucosamine varies among individuals. Studies provide mixed results. However, it has been very beneficial in my experience. During periods when I stopped taking it, my arthritis issues resurfaced but disappeared quickly once I resumed.

4. Glucosamine and Chondroitin taken as a supplement

Glucosamine and chondroitin are often taken together for joint health since they may work synergistically to support cartilage, reduce pain, and enhance joint function. Chondroitin, also to be found in human and animal cartilage, is used as a supplement to manage osteoarthritis symptoms, but in practice taken only together with Glucosamine, while Glucosamine is often used as a stand alone supplement.

Supplements typically provide 1,200 to 1,500 milligrams per day of Glucosamine and 500 milligrams of Chondroitin.

5. Benefits of Glucosamine (summary from internet sources)

1. Glucosamine may reduce joint pain, especially in osteoarthritis patients, improving joint functions.

2. It might aid in maintaining and potentially repairing cartilage.

3. Users often report enhanced joint flexibility and reduced discomfort.

4. Glucosamine may have inflammation-reducing properties.

5. Preliminary studies suggest potential benefits for other conditions, like rheumatoid arthritis.

6. Safety and Side Effects (also from internet)

Glucosamine and Chondroitin are usually safe. However, side effects can occur.

1. Possible digestive discomfort. 2. Allergic Reactions, particularly in those allergic to shellfish, as many supplements are shellfish-derived/ 3. Increased Blood Sugar: Concern for individuals with diabetes, though recent research suggests minimal impact. 4. Potential interaction with medications like blood thinners. 5. Blood Pressure**: Some report mild increases in blood pressure. 6. There are rare reports of headaches, drowsiness, or skin reactions.

Let us hope you do not need Glucosamine or any other supplement.

Live a happy and healthy life,

Robert, your health friend,

On dushi Curacao