Category: chapter 21

21. STAY HEALTHY: 100 GLASSES OF RED WINE DAILY OR …RESVERATROL/ PTEROSTILBENE?(health project99+)

Kenya, preparing for the great migration

Dear reader,

Some 20 years ago Resveratrol was the supplement to take. It was heavily promoted by longevity experts like Dr Sinclair. Resveratrol was also found naturally in wine. As a result, wine lovers jumped on the band wagon. More wine, for health benefits only of course.

To obtain a dose of Resveratrol that might have health benefits, one would need about 100 mg per day. This would require drinking approximately 100 to 1,000 glasses of red wine per day. I do not know about you, but drinking 100 glasses of red wine does not go hand in hand with longevity. This is true even for former diplomats.

In the end I decided for Pterostilbene and I stopped taking Resveratrol.

1.My thoughts about supplements in general

Before delving into the details of Resveratrol, let me first outline my general approach of this health project99+. The five key factors for longevity are: (1) diet, (2) stress management, (3) quality of sleep, (4) exercises and strength training, and (5) an active social life. 

By excelling in these five areas, you significantly increase your chances for a longer and healthier life. Supplements are the sixth category and, in my opinion, offer the most intriguing avenue for intervention.

Supplements provide hope—hope for a much longer life. Many studies are underway, and life is too short to wait for the results of all of them. Promising findings are emerging at an increasing pace, thanks in part to advancements in AI. I am among those open to taking certain supplements, even though their claimed effects are not yet scientifically proven. I adhere to the “do no harm” principle and choose to give them a try.

2.What can Resveratrol do? At first sight a lot.

Resveratrol is a natural polyphenol (see note below this blog on polyphenols). It has been detected in more than 70 plant species. It is especially found in grapes’ skin and seeds. It acts against pathogens (stuff that can make you ill), including bacteria and fungi. 

Many studies have demonstrated that Resveratrol possesses a very high antioxidant potential. It has other bioactive effects, like anti-inflammatory, anticarcinogenic (cancer), cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective. 

Longevity experts have been interested in Resveratrol since the early 2000s. Their interest increased particularly following research that suggested its potential role in promoting health and longevity. One study found that Resveratrol could trigger sirtuins. Sirtuins are proteins that are believed to play a crucial role in aging and metabolic regulation. Resveratrol was also linked to calorie restriction, an intervention that has been linked to increased lifespan.

3. One big problem with Resveratrol

Its half-time is low (max a few hours, some studies talk about 15 minutes) and its bioavailability is very limited. Some talk about a few percentages only, others about a maximum of 20%. This means that your body processes most of the supplement before it can do its work. The remainder that works lasts a very short time only. Very disappointing. This covers a wider theme that one should always consider when taking supplements. Omega-3 fatty acids last three days and most of the intake is being used.

4.Pterostilbene comes to the rescue/what is Pterostilbene?

Pterostilbene is a natural substance found in small quantities in vegetables and fruits such as blueberries. Those quantities, however, are so small. You need to take supplements for it to have an effect. Pterostilbene is chemically similar to Resveratrol. Both are compounds known as stilbenes. It is rapidly emerging as a supplement to watch.

5. Differences between Resveratrol and Pterostilbene

Pterostilbene is considerably better absorbed by the gut compared to resveratrol. Pterostilbene has a bioavailability of about 80 percent, compared to 20 percent for Resveratrol. Some studies suggest that the bioavailability of Resveratrol may be even as low as 1-3%.

Pterostilbene also has a longer half-life, which may allow it to be effective at lower doses. Around 2 hours for Pterostilbene and 15 minutes up to one hour for Resveratrol.

Studies have already reported that Pterostilbene can be superior to Resveratrol for certain health conditions. It has shown promise for improving cardiovascular health. Pterostilbene may also enhance glucose levels and cognitive function. One minus is that there are far fewer studies on Pterostilbene than on Resveratrol.

6. Pterostilbene and Longevity/What does Pterostilbene do? A lot

Many studies demonstrate beneficial effects of pterostilbene on health and the aging process. The benefits of pterostilbene are promising, and supplements are likely safe for most people. Still, much more research has to be done. Results with mice is one step, with humans another.

  • Pterostilbene reduces inflammation and improves DNA repair. It activates sirtuins which are enzymes that repair DNA and improve metabolism. These enzymes can extend health span and lifespan.
  • Pterostilbene is also an autophagy inducer. Autophagy is the process that clears up cellular waste that accumulates in the cells. During aging, autophagy is reduced. Pterostilbene can also trigger AMPK. AMPK is an important energy sensor in the cells. This activation, in turn, inhibits mTOR, a strong inhibitor of autophagy.
  • Pterostilbene increases the production of powerful antioxidant enzymes, protecting the cells against oxidative damage. Pterostilbene can improve brain functioning and can protect the brain.
  • Pterostilbene has also been shown to increase levels of other antioxidants. These antioxidants are linked to everything from improved detoxification to reduced oxidative stress in mitochondria. Mitochondria are the energy powerhouses of our cells. They play a role in most age-related diseases. They also make sure you have enough energy to function optimally.2. It may help fight or prevent cancer.
  • Several animal studies have found that supplementing with pterostilbene lowers blood glucose levels. This suggests that this antioxidant may play a role in protecting against diabetes. It may also improve insulin sensitivity.
  • Some evidence even suggests that Pterostilbene and Resveratrol may mimic the effects of calorie restriction. This practice has been shown to increase life span and help prevent age-related disorders.

7. Side Effects of Pterostilbene

Both can on rare occasions have some side-effects. They vary from gastrointestinal symptoms and headaches to fatigue. Rare interactions can occur with some medicines, like blood thinners or medications that are metabolized by the liver. Various studies show that Pterostilbene improves many other biomarkers of cardiovascular health, including lowering blood pressure. This could be problematic for people with already low blood pressure or those on antihypertensive medications.

A recent study suggests a small but significant increase in cholesterol. This change may occur at the normal dose of 100 mg of Pterostilbene. This effect is observed at least for people with a higher-than-normal BMI. But as mentioned before, more studies are necessary. Conducting human trials with all the variables is quite difficult.

8. My experience

After finding out more about Resveratrol I decided to swap it for Pterostilbene. I take several other supplements, so it is difficult to say if and how it works. I find the studies convincing. I never experienced any side effects. A question I want to explore further is how to have the positive influence of Pterostilbene the whole day. Its half-life is 2 hours. This implies that it only works 4 hours per day if you take two per day.

Some experts also believe that pterostilbene and resveratrol are better when consumed together. They act synergistically to promote health and prevent a variety of diseases. This is why you’ll often find them packaged together in supplements. I have not seen much about this, so I only take Pterostilbene.

Enjoy your life, think about the big 5, do not forget your pills,

Robert, your health friend

Note: you often read about “polyphenols”. This is a large and diverse group of 8000 compounds with potential health benefits. They occur as  compounds in plants and are known for their antioxidant properties and potential health benefits. They do not directly influence the plant’s growth, development, or reproduction. However, they play important roles in protecting plants from ultraviolet radiation, pathogens, and herbivores.

Note. However, as with many compounds, the exact half-life can vary based on factors such as the dosage, individual metabolism, and form of pterostilbene (e.g., whether it is taken as a supplement or comes from food sources). Additionally, pterostilbene is reported to have improved bioavailability compared to resveratrol, which may influence its effects in the body.

21. NICOTINAMIDE RIBOSIDE (=NR/NAD+), A SUPPLEMENT THAT BENEFITS HEALTH AND LONGEVITY (health project99+)

Somewhere in Southern Turkey

Dear reader,

I already wrote about three other life-extending supplements (berberine, fisetin and spermidine). Research is ongoing, but indications for all three are promising. This blog is about a fourth one, Nicotinamide riboside (NR). It is perhaps less known than the famous NMN. Still, it is probably more effective and is for sale in most countries (which NMN is not). I recently switched from NMN to NR.

NR intervenes on cellular level and compensates for the decline of certain cellular functions as we age.

1.My thoughts about supplements in general

Before delving into the details of NR, let me first outline my general approach. The five key factors for longevity are diet and hydration. Stress management is also essential. Don’t underestimate the importance of quality sleep and regular exercise. Finally, keep an active social life. By excelling in these five areas, you significantly increase your chances for a longer and healthier life. Supplements form a sixth category and, in my opinion, offer the most intriguing avenue for intervention.

Supplements provide hope—hope for a much longer life. Many studies are underway, and life is too short to wait for the results of all of them. Promising findings are emerging at an increasing pace, thanks in part to advancements in AI. I am among those open to taking certain supplements, even though their claimed effects are not yet scientifically proven. I adhere to the “do no harm” principle and choose to give them a try.

2.What is Nicotinamide riboside (NR)?

NR is a supplement with a potential life extending function. It is a form of vitamin B3. It is an efficient precursor to NAD+. It is the subject of many studies exploring its benefits for health and longevity. It exists in our daily diet as niacin and niacinamide and found in small amounts in milk. NR is efficiently taken up by cells, where it is converted into nicotinamide adenine dinucleotide (NAD+).

3.And what is nicotinamide adenine dinucleotide (NAD+)?

NAD+ is a coenzyme found in all living cells. It plays a crucial role in cellular metabolism, serving as an essential electron carrier in redox reactions. NAD+ is involved in several important biological processes, including energy production of cells, DNA repair, sirtuin activation and cell signaling. (More information on precursors, coenzymes, redox reactions, sirtuin activation, and cell signaling is provided at the end of this blog).

NAD+ is crucial for cellular metabolism and repair. It is a fundamental target for interventions. These interventions aim to promote long-term health. (I know it sounds like an advertisement, sorry about this).

4. Levels of NAD+ decline with age. This decline has sparked interest in its potential therapeutic use for conditions related to aging. It is also being considered for energy metabolism. Additionally, it may help with various degenerative diseases. The concept is easy: more NR will lead to better level of NAD+.

5.A bit more about the functions of NAD+

NAD+ is a fundamental component of our energy metabolism, essential for converting food into usable energy. It contributes to ATP, the energy currency of the cell. 

NAD+ is involved in the role of enzymes like PARPs (Poly ADP-Ribose Polymerases). These enzymes repair damaged DNA. As a result, they maintain the integrity of the genome.

NAD+ activates sirtuins, which are a class of proteins. These proteins regulate cellular health, aging, and longevity. Some scientists suspect that cells and humans last longer. They suspect humans age more slowly as sirtuin-1 in their cells is better able to carry out its function. They believe this could be achieved by increasing the concentration of NAD+ in cells.

NAD+ also acts as a precursor for the synthesis of molecules like cyclic ADP-ribose, which are involved in cell signaling.

6.There is more to NR than only contributing to higher levels of NAD+

Over 100 preclinical studies have been published on NR (nicotinamide riboside). We’re starting to see numerous publications on disease states. Some are just age-related indications. Others are actually disease states. Remarkably, there is incredible consistency with positive results.  

Animal models have shown that NR can increase NAD+ levels. They might exert potential benefits related to aging, energy metabolism, and cellular health. However, human studies are still developing.

There are peer-reviewed published clinical studies on inflammation-related disorders. They range from the lungs to the brain, muscle, and heart. Diseases related to mitochondrial function seem to benefit. One of the most notable diseases is Parkinson’s disease. It is also the furthest along in benefiting.

7.Some last words about NR, NMN and NAD

NR and NMN are close enough to consider both. Chemically they are the same, but NMN has an extra phosphate group, which makes NMN bigger. This phosphate group has first to be eliminated before it can enter a cell, unlike NR that can enter directly.

NMN is not for sale in many countries. This includes The Netherlands. This is one (but not the only) reason why I go for NR. 

Be careful with NAD boosters. Companies sell NAD, which is a bad idea. The NAD molecule is a very large molecule. When you ingest it, it enters the bloodstream. It tries to get into the cell and fails. That try, which is dramatic with NAD, a little less dramatic with NMN, causes friction and inflammation. 

The phosphate does eventually breaks off. The NAD molecule breaks apart into smaller molecules. One of these molecules is actually NR. This NR enters into the cell very cleanly and efficiently. It then eventually converts back into NAD once inside the cell. 

8.Is NR safe?

NR is generally considered safe when used appropriately and has a good safety profile based on current studies. If you have a history of liver disease, do not take nicotinamide — even at low doses.

Enough food for thought I would say. Take care and live a happy and healthy life!

Robert, your health friend

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Explication of some of the terms used in bullit no 3.

Precursor = In biochemical terms, a precursor is a compound that participates in the chemical reaction that produces another compound. For example, amino acids are precursors to proteins, and cholesterol is a precursor to steroid hormones.

Co-enzyme = A coenzyme is a non-protein organic molecule that binds to an enzyme and is essential for the enzyme’s activity. Coenzymes work by helping enzymes catalyze reactions that occur in cells. They often act as carriers for chemical groups or electrons, facilitating the transformation of substrates (the molecules upon which enzymes act) into products. Many coenzymes are derived from vitamins, which is why vitamins are crucial for maintaining cellular function and overall health. NAD+ is one of the best-known coenzymes.

Redox = Redox is short for reduction-oxidation, which refers to a type of chemical reaction involving the transfer of electrons between two species. These reactions are essential to many biological and industrial processes and can be characterized by changes in the oxidation states of the species involved. Redox reactions are fundamental to many processes, such as cellular respiration, photosynthesis, combustion, corrosion, and various industrial chemical processes.

Sirtuin activation = NAD+ is een molecuul dat belangrijke enzymen in de cel in staat stelt om hun werk te doen. Daarbij zitten ook enzymen die biochemici sirtuïnes noemen. Een hele belangrijke is sirtuïne-1. Dat enzym stelt menselijke cellen in staat om zichzelf te repareren.

Cell signaling = Cell signaling is the complex system of communication that governs basic cellular activities and coordinates cell actions. It is a vital process by which cells communicate with each other and respond to external and internal stimuli. This communication is essential for the development, function, and survival of all cells and organs in living organisms.

21. SPERMIDINE: THE ZOMBIE CELL KILLER (health project99+)

Pelicans in the Caribbean

Before writing about the next specific supplement (spermidine), allow me to describe my vision. As always, I will explain the place of supplements in the whole chain of life-improving and extending measures.

1.Introduction

You have the big five. I do not mean  the African safari animals, but the five groups of interventions that are important for longevity. The big five for longevity are food/drinks, stress, sleep, exercise and social life. Do these five well, and you increase your chances for a longer and more healthy life. You will especially boost your chances for a much longer healthy lifespan. Do not underestimate the importance of this last point. Studies indicate that more than half of the people above 60 in the Western world face serious health problems. These issues prevent them from enjoying the remaining 20+ years of their life as they should and could.

2. Potential of supplements in general

So what about supplements? The so-called 6th wheel on the wagon. Some supplements are there to reinforce the good work within the big 5. Some are often useless, like vitamin C or Omega-3. However, other supplements offer hope. Hope for a much longer life. Many studies are ongoing and life is too short to await the results of all of them. Promising results are coming in in an accelerating way, also thanks to AI. I am one of those who is open to taking certain supplements. Their claimed effects are not yet scientifically proven. I follow the no-harm principle and go for it. 

Earlier I write about two lesser-known supplements that give me much hope: berberine and fisetin. Fisetin might add 10 – 40% to the lifespan and improve health quality as well. It also mimics the effects of intermitted fasting. Berberine supports blood sugar management and its other potential benefits. It interests me mainly because it may slow aging. It could extend life expectancy by years, not just months.

This time I write about spermidine, a supplement I take once daily (5 mg).

3. What is spermidine?

Spermidine is present in all organisms, including plants, animals, and microorganisms. In humans, it can be obtained from dietary sources such as whole grains, soy products, aged cheese, and mushrooms. Other sources include legumes and certain fruits and vegetables. It is also synthesized endogenously in the body.

4. Its name? Yes, indeed

The name “spermidine” originates from its discovery in semen. Spermidine is a polyamine compound that was first extracted from seminal fluid, which led to its name. The Latin word “sperma” means semen. “Spermidine” was named this way because it was initially identified as a significant component in sperm cells.

5. Spermidine: I go for autophagy

Spermidine is a longevity agent in mammals due to various mechanisms of action, which are just beginning to be understood. It is a naturally occurring polyamine compound found widely in living cells. It stabilizes DNA and facilitates protein synthesis. These actions make it essential for maintaining cellular functions.

The claims about spermidine are manifold; for me the most appealing part is the role it plays in autophagy. Autophagy is a cellular process that involves the degradation and recycling of damaged cellular components, helping to maintain cellular health. Spermidine may contribute to improved cellular function by promoting autophagy. This improvement could play a role in slowing down the aging process. It may also potentially increase lifespan. I am all in favor of this!

It is not only autophagy what spermidine influences. Research suggests that by promoting autophagy, spermidine might contribute to increased lifespan and cardiovascular health. It may also offer neuroprotection, including cognitive function, and metabolic health. More human studies are needed to confirm these effects. There is also evidence found for impact on other mechanisms. These include inflammation reduction, lipid metabolism, and regulation of cell growth and proliferation. 

6. What are polyamines?

Polyamines are organic compounds characterized by having two or more amino groups. They are essential for cellular functions and are found in all living organisms. The most common polyamines in biological systems are putrescine, spermidine, and spermine.

7. Why take spermidine?

Your body produces spermidine and food provides it as well. However, as we age, the body’s ability to synthesize spermidine decreases. This reduction may contribute to some age-related cellular and physiological changes. This decline is part of why researchers are looking into spermidine supplementation. They are exploring dietary sources to promote healthy aging. These sources may support cellular health. For me it an important reason to take this supplement with, as said, the main focus on autophagy. “Clean those dead cells” is a slogan that appeals to me. I am very willing to take the necessary supplements.

8. Spermidine uses in treatment of diseases.

In recent years, spermidine has attracted attention for its potential health benefits, particularly in the context of aging and longevity. Spermidine is reported to reverse the aging process and enhance cardiovascular in animal studies. Aged mice administered spermidine had healthier hearts and improvements in metabolic activities. Numerous research studies have investigated the anti-aging properties as well. Several animal studies have demonstrated that administering spermidine can aid in the prevention of certain cancers. It seems that first human studies confirm the findings of animal research.

The body’s spermidine synthesis decreases with age. It becomes progressively difficult for your body to activate autophagy without an adequate spermidine level. This contributes to aging. This can be regenerated for older adults by consuming a diet rich in spermidine or, more effectively, by taking supplements. Synthetic spermidine mimics the naturally occurring molecules in every way. 

9. Side Effects? 

Because spermidine is a naturally occurring substance in the body, it is thought to be completely safe. Long trials have shown that the supplement has no adverse side effects. This is true even when taking high doses, up to 6 milligrams daily.

10. Dosage?

There is a debate among specialists about the required dosage. Global estimates of spermidine consumption range between 5 mg and 12 mg per day via dietary sources.

As mentioned spermidine is a naturally occurring polyamine found in various foods, particularly certain vegetables. Some of the vegetables with the highest spermidine content include broccoli. Cauliflower also contains a few mg per 100 grams of fresh weight of vegetables.

Dr. Sinclair takes about 1 mg of spermidine per day. I do 5 mg per day.

11. 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 spermidine, 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. So, more research is crucial to confirm these effects in humans.

13. Weak Points of Supplements (in general)

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. My advice is not to be guided by price.

2. Many health claims are not scientifically proven.

14. Which is better, NMN or spermidine?

Spermidine powder inhibits aging via autophagy, but NMN powder can have anti-aging benefits by increasing NAD+ levels in the body. Scientists suggest there may be synergistic benefits when NMN and spermidine are combined. This combination might be a potential strategy for enhancing health in elderly people. Interesting and something I follow closely.

Take care and live a happy and healthy life,

Robert, your health friend

Flamingos in the Venezuelan estado de Falcon

21. FISETIN, A SUPPLEMENT THAT MIGHT ADD YEARS TO YOUR LIFE (health project99+)

Colonial Tovar in Venezuela

Summary An exciting supplement showing a lot of potential is Fisetin. Animal studies suggest that taking Fisetin can add 10% (some claims are much higher) to the lifespan and improve health quality. It also mimics the effects of intermitted fasting. 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.

3a. 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.

3b. 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.

4. 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.

5. 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.

6. Weak Points of Supplements (in general)

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. My advice is not to be guided by price.

2. Many health claims are not scientifically proven.

7. Where do supplements rank in the path 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