What are some of the best supplements for longevity?
Which are the anti-aging supplements I take as a medical doctor and longevity hacker?
First, it’s important to differentiate between “longevity supplements” and “health supplements”:
“Longevity supplements” act on the aging process with the aim of slowing down aging and extending lifespan. These are substances like fisetin, microdosed lithium, alpha ketoglutarate (AKG), and so on.
“Health supplements” are vitamins, minerals and other micronutrients that in most cases unfortunately don’t extend maximum lifespan, but that can shorten lifespan and/or reduce quality of life if you are deficient in them. These are substances like vitamin D, potassium, vitamin A, B vitamins, and so on.
Health supplements are still important though. Most people are deficient in these micronutrients, even if they eat “healthy”. Some important reasons why so many people are deficient are the following:
- Our bodies are not well made by nature to properly take up all micronutrients
- Many of our foods are very different now compared to thousands of years ago, or even 100 years ago, containing less micronutrients and/or being more unhealthy
- Nature (evolution) doesn’t care for us to have a long lifespan, so it has not perfected our body to absorb all needed micronutrients for a long, healthy life
- Our modern way of life exposes us to many stressors, requiring us to take in more micronutrients (stress and alcohol require more magnesium and B vitamins, sitting inside the whole day leads to vitamin D deficiency, etc).
- Many official recommended amounts of micronutrients are too low for optimal longevity, and are based on old or crude measurements and research
- Even when eating “healthily”, it’s very difficult to get all required micronutrients via food.
- When we get older, our body becomes less and less able to properly absorb nutrients (e.g. our skin is less able to produce vitamin D, our stomach and gut absorb less micronutrients, and so on).
So in general, “health supplements” are important. You can take the best “longevity supplements”, but if you are still deficient in iodine or omega-3 fatty acids you still will shorten your lifespan and undermine long-term health.
In fact, a lifelong deficiency in just one micronutrient, like iodine, calcium or a specific B vitamin, could substantially wreak havoc on your health and increase your risk of many diseases.
In this article, we will first concentrate on the best longevity supplements, and then discuss the most important health supplements.
By writing “best” longevity supplements, I refer to substances that have the best and most convincing science and data behind them to slow down aging and extend lifespan.
These supplements are often a far cry away from many so-called “anti-aging” supplements that often are very popular but that don’t extend lifespan, or have very little or no science behind them. Some of these could even accelerate aging or increase mortality.
In other words, you might be surprised that you don’t find many antioxidants or popular “anti-aging” vitamins or minerals in this longevity stack: most of these do not slow down aging or extend lifespan. This includes popular “anti-aging” substances like coenzyme Q10, ubiquinol, acetyl-cysteine (ACL), nicotinamide riboside (NR), and many others.
Despite that for some of these ingredients there are scientific studies showing they can indeed extend lifespan, there are many more studies showing they don’t extend lifespan, or even worse, can shorten lifespan. So I would be careful with these supplements.
Other anti-aging supplements I included may also surprise some, but in a positive way, like glucosamine or chondroitin, which are mainly used for joint health, but have been shown to slow aging and extend lifespan in many studies.
So, in no particular order, we have the following science-based anti-aging supplements:
MICRONUTRIENTS VIA FOOD
1. Microdosed lithium
Lithium is a mineral found in rocks. From rocks, it seeps into water, eventually ending up in drinking water.
There are regions in the world where the drinking water is higher in lithium. Interestingly, scientists discovered that in these regions there is less mortality, less Alzheimer’s disease, less suicide, and even less crime (R,R,R,R,R,R,R).
This hinted to researchers that lithium, at low doses, could slow down aging, improve brain health and stabilize or improve mood, explaining why in regions with higher amounts of lithium in the drinking water there seems to be less suicide and crime.
That lithium could reduce the risk of Alzheimer’s is very interesting. Currently, we have no drugs that can significantly impact the disease. Prevention is very important therefore. A study found that people who were exposed to lithium (red graph) had significantly less risk of Alzheimer’s disease and other kinds of dementia (R):
Many of these studies involve people who took lithium as a drug, often because they have bipolar disorder (also called “manic-depressive disorder”).
Normally, people with bipolar disorder have a substantially increased risk of dementia.
However, that people with bipolar disorder who took lithium had actually less risk of dementia could indicate that lithium can significantly reduce the risk of dementia.
However, the doses of lithium given to bipolar patients are far higher compared to the doses of lithium one finds in drinking water, or “micro-dosed lithium”.
In psychiatric settings, doses of lithium are given that are hundreds of times higher compared to the micro-doses for longevity.
For example, to treat bipolar disorder, lithium is given in doses of a few hundred milligram of lithium per day, while in the context of longevity micro-dosed lithium is given, mostly in the range of 0.3 to 5 mg of pure lithium per day.
Despite the much lower doses of microdosed lithium, we see nonetheless that lithium in these dose ranges still has many beneficial effects for health and longevity.
And this especially for brain health. For example, clinical trials in humans in which participants took microdosed lithium showed improvements in Alzheimer’s diseases and mild-cognitive impairment (R,R,R), ideally when the trials last long enough (6 months or longer).
How lithium can slow aging
Lithium positively impacts many fundamental aging mechanisms.
Lithium also induces autophagy (R) which is the breakdown of proteins and other materials that would otherwise accumulate in the cells, an important process contributing to aging.
Does lithium cause kidney damage?
Some people worry that lithium can damage the kidneys.
After all, there have been many studies showing that lithium can damage the kidney.
However, this only when lithium is given in very high doses, in psychiatric settings. There, doses are given that are many hundreds of times higher than micro-dosed lithium for longevity purposes.
At such high doses, and when given chronically for years, lithium could indeed damage the kidneys. However, for micro-dosed lithium this is not the case: these low doses of lithium do not damage the kidneys.
According to Dr. Rujun Gong:
“Lithium may emerge as an effective anti-aging medication for the kidney and potentially other organ systems and help to better preserve the health and well-being of our aging population.”
– Dr. Gong, Division of Nephrology, Department of Medicine Center for Hypertension and Precision Medicine, University of Toledo College of Medicine, USA
In conclusion, low doses of lithium could actually protect the kidneys.
Optimal lithium for longevity dose: 0.3 mg to 5 mg per day.
2. Chondroitin sulfate
Chondroitin is an important component of cartilage, and of the extracellular matrix (ECM).
The extracellular matrix is a crucial substance in our body. It’s the viscous, sticky, gel-like matter in which all our cells are embedded and that functions as the glue that makes stick together our cells.
Without the ECM we would fall apart and be a big pile of individual cells.
The ECM consists of chondroitin, hyaluronic acid, collagen, elastin and other long, strand-like structures that give firmness to our tissues, including our skin and joints. This is also why chondroitin is often taken as a supplement to improve joint health.
However, most people don’t know that chondroitin also is a very interesting anti-aging supplement, which has been shown to activate various pro-longevity pathways, and to extend lifespan (R).
In humans, intake of chondroitin has been associated with reduced mortality (R). It’s one of the very few supplements that is associated with reduced risk of death and improved health.
It’s interesting to note that other molecules that are part of the extracellular matrix (ECM), like hyaluronic acid (which we will also discuss) and glucosamine, also extend lifespan in multiple species and have been associated with reduced mortality and aging-related diseases in humans (see further down).
In other words, these and other studies hint that extracellular matrix components could be interesting lifespan molecules.
In this regard, it’s not surprising that combining chondroitin with these ECM molecules could yield even better effects. For example, combining chondroitin with glucosamine has been associated with 65% reduction in cardiovascular mortality, and a 39% reduction in all-cause mortality in humans (R). Other studies also find reductions in mortality in humans who take chondroitin and glucosamine (R).
How chondroitin slows down aging
There are many ways in which chondroitin can slow aging and keep us healthier for longer.
For example, chondroitin has been shown to reduce inflammation. Chondroitin also can activate genes that encode components of the extracellular matrix. A strong extracellular matrix protects and maintains our cells better, including our stem cells.
Chondroitin can also mitigate atherosclerosis by improving the health of the cells that line the blood vessels (R). This can help to explain why studies show an association with chondroitin intake and significantly reduced risk of cardiovascular mortality in humans (R).
Besides the beneficial effect of chondroitin on lifespan, hearth health and other diseases, it can also improve skin health (R), which makes sense given chondroitin is an important component of the skin.
It’s important to take the chondroitin sulfate form, not the plain chondroitin form (e.g. chondroitin HCl or chondroitin KCl). The chondroitin sulfate is the same form that occurs in our body.
Ideally, one combines chondroitin sulfate with glucosamine sulfate (see further below) for maximum longevity benefits.
Longevity dose: 1200 mg per day (1000 to 1500 mg per day)
3. Glucosamine sulfate
Just like chondroitin, glucosamine sulfate is an important component of the extracellular matrix (ECM), the glue that embeds our cells, gluing them together. Glucosamine is an important component of our skin and joints.
Glucosamine is often promoted as a supplement to improve joint health. However, glucosamine is also a very interesting longevity substance.
Glucosamine and longevity
People who take glucosamine also had less heart disease and cardiovascular mortality (R,R,R,R). A study published in the British Medical Journal (a very reputable medical journal) looked at the data of almost half a million people and found that glucosamine use was associated with 22% less cardiovascular death (R).
Interestingly, one study found a large risk reduction from death from respiratory diseases (a 41% reduction) in people who take glucosamine (R). This could make sense, given lung tissue is a very elastic, flexible tissue which is very dependent on a proper extracellular matrix, which is composed of molecules like glucosamine (and chondroitin).
According to the conclusions of scientists who conducted a large glucosamine study, “regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases”.
It’s even better to combine glucosamine sulfate with chondroitin sulfate. Studies show that this combination can significantly reduce the risk of dying in humans.
How glucosamine can slow aging
Does glucosamine improve joint health?
A little word here about glucosamine supplements for joint problems, specifically osteoarthritis.
As we age, osteoarthritis becomes sooner or later a significant problem for almost everyone. Osteoarthritis is the wearing down of our joints, specifically the cartilage that lines our joints.
There exists lots of contradictory studies about glucosamine and joint health: some studies show that glucosamine can improve joint health, while others don’t show an effect.
Still today people, including doctors, claim that glucosamine supplements do not work to improve osteoarthritis.
To make a long story short, glucosamine very likely also improves joint health, least according to well-conducted studies.
The problem is that many studies done with glucosamine (and which don’t show an effect), have been done in a substandard way. For example:
- The studies often didn’t last long enough; like only a couple of months or even weeks. Mostly, damaged joints take a long time to heal.
- Many studies didn’t use high enough doses.
- Many studies used plain glucosamine (e.g. glucosamine HCL) instead of glucosamine sulfate (the latter form is preferred).
- Many studies use low-quality glucosamine (sulfate) supplements, or they use non-crystalline glucosamine sulfate supplements. High-quality, crystalline glucosamine reaches the joints in higher concentrations much better.
So it’s important to use high-quality, ideally more crystalline glucosamine sulfate supplements for a long enough time to get an effect.
In light of the innumerable animal and human studies showing beneficial effects of glucosamine on aging, improving many aging-related diseases and reducing mortality, it’s very likely that high-quality glucosamine in the right form and dose given long enough would also benefit our joints.
And as mentioned before, ideally glucosamine is combined with other important components of our joints and cartilage, namely chondroitin sulfate and hyaluronic acid, two extracellular matrix substances which also, not coincidentally, have been shown to extend lifespan and improve healthspan.
Ideal dose of glucosamine sulfate (not plain glucosamine): 1200 mg per day (1000 to 1500 mg per day).
Fisetin also has been shown to improve various aging-related diseases, or to improve diseases that involve aging-related mechanisms such as protein accumulation (as in Hungtinton disease for example, in which a specific protein accumulates in the brain).
In a Hungtinton disease model, mice were given fisetin. While the control mice only lived on average for 104 days, the lifespan of the fisetin-fed mice was about 30% longer (139 days) (R).
Huntington’s disease is a deadly neurodegenerative disease in which a protein accumulates in the brain (huntingtin), leading to specific brain regions to die off. During aging, various other brain proteins accumulate (like beta amyloid, tau, TDP-43, and many others).
Is fisetin really a senolytic?
Often, fisetin is touted as a “senolytic” substance, implying it would be able to destroy senescent cells.
This could – perhaps- be the case when fisetin is given in very high doses, e.g. 1200 mg per day in humans during 3 days every month to “kill off” senescent cells.
However, at such high doses, it could be that fisetin (like quercetin) also damages healthy, normal cells, especially stem cells.
After all, many senolytics are “dirty senolytics”, meaning they do not only kill or damage senescent cells but can also kill or damage normal, healthy cells, including stem cells.
Interestingly, in mice lifespan studies, fisetin is given in relatively low doses. At lower doses, fisetin is likely not a senolytic. So it likely exerts its effects via other mechanisms than by being a senolytic.
Fisetin could even have similarly strong anti-inflammatory activity as ibuprofen, a well-known anti-inflammatory drug (called “NSAID” or “Non-Steroidal Anti-Inflammatory Drug”) (R).
Additionally, fisetin inhibits an important pro-aging pathway, namely the PI3/AKT-mTOR pathway (R,R). Inhibiting mTOR has been shown to extend lifespan in multiple species, as we will discuss later on.
Fisetin can also be an “indirect antioxidant”, meaning that it can induce transcription factors (like NRF2) that latch onto the DNA and upregulate the production of our own cellular antioxidant proteins, which is much better than taking direct antioxidants (like some vitamins and other “antioxidants”), which in most cases don’t extend lifespan.
In this regard, fisetin seems to be a special kid on the block regarding flavonoids. Flavonoids are found in healthy foods like fruits, vegetables and green tea for example, and are an important reason why these foods are healthy.
There exist many different flavonoids (e.g.flavonols, flavones, anthocyanidins, isoflavones, flavanones, flavan-3-ols, etc).
However, when looking at dozens of them, only two (fisetin and quercetin) were for example able to maintain glutathione (GSH) levels, which can combat oxidative stress.
Fisetin was also among the very few flavonoids shown to possess neurotrophic activity, for example by increasing the amount of neurites (these are projections from brain cells that make connections with other brain cells) (R).
Fisetin could also be beneficial for brain health and brain aging, for example by inhibiting the accumulation of beta amyloid protein, improving blood vessel health in the brain, and by reducing inflammation in the brain (neuroinflammation) (R,R,R,R,R).
“Fisetin dramatically improved the treatment outcomes of the patients with stroke, as revealed by lower National Institute of Health Stroke Scale (NIHSS) scores. The beneficial effect of fisetin was likely attributable to reduced levels of MMP-2, MMP-9 [matrix metalloproteinases, which are proteins that break down the extracellular matrix], and CRP [a proinflammatory protein] in the serum, as evidenced by strong linear correlations between serum levels of such markers with the NIHSS scores in all enrolled patients.”
5. Nicotinamide mononucleotide (NMN)
Nicotinamide mononucleotide (NMN) is a precursor of a very important compound found in all our cells, namely NAD+ (nicotinamide adenine dinucleotide).
NAD+ is central for proper cellular functioning. It’s a relatively small molecule providing energy to innumerable proteins in our cells so they can carry out their function.
For example, NAD+ is needed for sirtuins and PARP proteins to repair our DNA and maintain our epigenome.
Administering NMN increases levels of NAD+. Many studies show that NMN can improve various aspects of the aging process, such as:
- Improving blood vessel health (R,R,R,R,R).
- Improving stem cell health (R,R).
- Improving metabolism, including glucose intolerance, hepatic insulin sensitivity, lipid metabolism
- Restoring gene expression related to inflammation, oxidative stress and circadian rhythms (R).
- Improve fertility (R).
As you can see, NMN has many beneficial, anti-aging effects.
Let’s first go a bit deeper into the effects of NMN on fertility.
NMN and fertility
NMN has been shown to improve the health of egg cells (oocytes). That’s very interesting, because egg cells are in fact giant stem cells; once fertilized, just one egg cell keeps dividing until it has sprouted the 40,000 billions cells of which a human is composed.
NMN has shown to counteract various aging processes in egg cells, which could imply that NMN could also benefit stem cell health, which indeed seems to be shown by other studies demonstrating that NMN can improve stem cell function (R,R).
Interestingly, there are various case studies in which elderly women who have been in menopause for years, started to ovulate again after taking NMN.
Furthermore, specific companies have been using NMN and NMN analogues to rekindle fertility in old mares, or keep them fertile for longer.
Can NMN extend lifespan?
There are lots of studies showing that NMN can improve various aspects of aging or aging-related diseases in animals. But can it also extend their lifespan?
According to preliminary experiments done by professor David Sinclair, NMN can also extend lifespan in normal, healthy mice.
The words “normal and healthy” are important here, given that in many “longevity” studies diseased animals are used, e.g. animals that have deliberate mutations that cause a specific disease (like Alzheimer’s disease or a mitochondrial disease).
The way these animals age, or even have a specific disease, is often very different from how normal healthy animals age, or how humans have the specific disease in question.
Given NMN can extend lifespan of normal, healthy mice, and not of diseased, abnormal mice is very interesting.
However, even in the case NMN could not extend lifespan, it could very likely make old age a lot more fun. This by reducing or slowing down various aging-related diseases or mitigating aging-symptoms.
Let’s look at some effects of NMN in humans.
Effects of NMN in humans
In humans, NMN has been shown to improve insulin sensitivity in pre-diabetic women (R). This is a good thing, given that during aging, insulin resistance increases, which in turn increases the risk of various aging-related diseases such as heart disease and Alzheimer’s disease, and of aging itself.
NMN also enhanced muscular health in elderly men (R). During aging, muscle health and strength diminishes, which leads to reduced mobility, an increased risk of falls and many other problems.
NMN can also increase endurance in humans, providing more energy and stamina (R).
Can NMN be taken orally (by mouth)?
It’s important to note that in the human studies we just discussed, NMN is taken via mouth (orally), so not injected intravenously or taken sublingually ( dissolved under the tongue).
It also involves normal, plain NMN powder (not liposomal NMN), and is given in most studies in doses of around 250 mg of NMN per day.
I mention this because some people believe that NMN should be taken singlingually or even intravenously, which is not the case.
Lots of people also think that NMN should be taken in liposomal form – which means it would need to be encapsulated in tiny fat droplets to improve its absorption. This is all not necessary. Orally taken, non-liposomal NMN works fine, as these studies demonstrate.
For people still doubting, one of the most renowned specialists in NMN, Harvard Professor David Sinclair, takes normal, non-liposomal NMN during breakfast (so orally, not sublingually).
Professor Sinclair however takes a high dose of NMN – around 1000 mg per day. But such a high dose is not necessarily needed. We see that in most human studies around 250 mg of NMN per day already has beneficial effects (R,R,R).
Nonetheless, it could be that higher doses could be even more beneficial; especially as one gets older.
Therefore, one recommendation is taking around 250 to 500 mg for people in their thirties and forties, and around 600 mg to 750 mg per day for people in their fifties and sixties, and 750 mg to 1000 mg per day for 70-plus people.
However, one should be mindful not to take too much NMN. We see that likely from doses of more than 2000 mg per day the beneficial effects of NMN are actually reduced.
It’s also advised to take NMN in the morning, because NMN taken at noon or in the evening, can give some people too much energy in the sense it hinders them from falling asleep at night.
6. Alpha-ketoglutarate (AKG), the calcium form
Alpha-ketoglutarate (AKG) is a substance found in every cell in our body. It’s actually an important fuel for our mitochondria, the power plants of our cells.
Studies show that alpha-ketoglutarate extends lifespan in multiple species.
In some preliminary human studies, alpha-ketoglutarate could rejuvenate humans, measured via epigenetic clocks (R).
How alpha-ketoglutarate slows aging
Alpha-ketoglutarate is involved in the production of energy. To be more precise, alpha-ketoglutarate is a metabolite of the Krebs cycle, which is the chemical process in the mitochondria that creates most of the energy for our cells.
But AKG has many other functions in the body.
For example, AKG is involved in epigenetic regulation. The epigenome determines which genes are activated or not. A decline in epigenetic function plays an important role in aging, as we explained in the chapter about the causes of aging.
Alpha-ketoglutarate plays an important role in organizing and maintaining the epigenome, given TET enzymes need alpha-ketoglutarate to function properly. TET enzymes are important regulators of the epigenome; they remove methyl groups from DNA. To do this, they need alpha-ketoglutarate. And vitamin C. So in this regard, vitamin C works synergistically with alpha-ketoglutarate.
That’s why vitamin C also has epigenetic effects, and is also an important substance for optimal longevity, as I’ll explain later.
Best form of alpha-ketoglutarate
It’s important to take the calcium form alpha-ketoglutarate, namely “calcium alpha-ketoglutarate”, instead of the regular “alpha-ketoglutarate” (as most supplements contain).
It’s the calcium AKG form that has been used in scientific experiments demonstrating lifespan extension.
Scientists believe that the calcium atom in the calcium alpha-ketoglutarate compound stabilizes the alpha-ketoglutarate, and also slows down its absorption, prolonging its effect.
I take 2,000 mg of calcium alpha-ketoglutarate per day.
Glycine is a small amino acid that occurs naturally in our body.
Studies in humans show that if you give glycine to people, it can reduce inflammation (R,R) , enhance glucose metabolism (R,R,R,R) and improve aspects of aging (R), including degenerative diseases like osteoarthritis and osteoporosis (R).
Glycine also has a calming, relaxing effect. Therefore it’s best to take it before sleep.
Longevity dose for glycine: 2,000 mg per day
8. Hyaluronic acid
Hyaluronic acid is an important substance for our skin and joints.
In fact, hyaluronic acid is found everywhere in the body given that it’s an important component of the glue that makes our cells stick together.
Hyaluronic acid is part of the extracellular matrix (ECM), which surrounds our cells and glues cells together. Without an extracellular matrix, we would be a pile of cells lying on the floor.
Hyaluronic acid has been shown to have interesting lifespan effects. Components of hyaluronic acid like acetyl-glucosamine have been shown to extend lifespan in animals (R). Hyaluronic acid on itself also can extend lifespan (R).
Interestingly, one of the reasons why naked mole rats live much longer than normal rats, is due to the fact they produce more and stronger hyaluronic acid. More specifically, they produce hyaluronic acid with a higher molecular mass (R). This kind of hyaluronic acid protects their cells better, and also reduces the risk of cancer cells metastasizing (spreading) because thicker hyaluronic acid means it’s more difficult for cancer cells to penetrate tissues.
Increasing enzymes that make hyaluronic acid also increases lifespan in mice (R).
However, most people will know hyaluronic acid as an ingredient in skin creams and serums to reduce wrinkles. Given hyaluronic acid is very good at attracting water, it can make our skin more moisturized, making it look less dried-out, and thus younger.
However, when taken orally, hyaluronic acid can also reduce wrinkles – in a better and more fundamental way then via skin creams.
The reason for this is that when taken orally, hyaluronic acid is broken down into smaller components in the gut. These parts are then taken up from the gut into the bloodstream (R,R), reaching our skin cells and nudging them to produce more hyaluronic acid, leading to reduced wrinkles and a younger-looking skin (R,R,R,R).
There are different forms of hyaluronic acid. A good manufacturer of hyaluronic acid is Hyabest (this form of hyaluronic acid has been tested clinically in various studies, demonstrating improvements in skin appearance).
Dose I take: 120 mg of hyaluronic acid before bed.
Magnesium is a mineral with many important functions in our body. Magnesium is needed by hundreds of proteins to function properly. Magnesium sticks to these proteins, enabling them to carry out their function.
Magnesium also protects DNA against damage (R,R,R). It can do this in various ways. Magnesium stabilizes DNA by gently “sticking” to the DNA strand. Magnesium is also an important cofactor for enzymes that repair DNA (e.g. base excision repair enzymes) (R), and binds to the DNA polymerase enzyme, which is needed for DNA synthesis and repair (R).
Studies show that people taking extra magnesium have less DNA damage (R).
Higher intakes of magnesium have also been associated with less inflammation (R).
Unfortunately, most people in the west (some studies estimate 75% of people) do not take enough magnesium.
It’s important to get enough magnesium, and this via foods and supplements. Various healthy foods contain magnesium, such as nuts (almonds and cashews), seeds (especially pumpkin seed and chia seeds), vegetables (spinach), fruits like avocado, legumes, and dark chocolate.
Ideally, you get all your magnesium via food, but even when eating “healthily” it’s difficult to take in sufficient amounts of magnesium on a daily basis (ideally around 350 to 500 mg per day). Therefore, it’s recommended to also take magnesium supplements, especially given the importance of this mineral for health and longevity.
However, most magnesium supplements are not ideal. There exist different forms of magnesium.
Most supplements use the magnesium oxide form. This is not an ideal form. Firstly, magnesium oxide has significant laxative effects. In fact, magnesium oxide was used in earlier times as a laxative.
Due to its laxative effects and given it’s less soluble than many other forms of magnesium, magnesium oxide is often less properly absorbed (though some studies dispute this).
However, most importantly, magnesium oxide is not an ideal magnesium form for longevity. It’s better to use forms of magnesium of which the salt (the molecule to which magnesium is bound) has been shown to extend lifespan and healthspan, such as glycine and malate.
In other words, “magnesium glycinate” and “magnesium malate” are preferred instead of magnesium oxide. Glycine has shown to extend lifespan (as we discussed earlier), as does malate.
Given glycine can also calm down the nervous system, one could take magnesium glycinate in the evening, before bedtime. Malate on the other hand can also provide more energy (it’s a naturally occurring fuel for our mitochondria), so ideally one takes it in the morning. But everyone is different, so try to find out which form of magnesium works best for you.
By taking magnesium malate or magnesium glycinate instead of magnesium oxide, you hit
two health birds with one stone: you both increase your intake of magnesium, and of a healthy longevity substance (like glycine or malate).
However, given one needs to take high amounts of these substances, it’s almost impossible to take them in a supplement (pill) form.
For example, to get around 350 mg of pure magnesium one would need to take around 2,300 mg (2.3 grams) of magnesium malate.
Magnesium malate consists of both a magnesium atom and the malate molecule. In fact, only 15% of the total weight of magnesium malate comes from magnesium, the other 85% of the weight is from the malate molecule.
That would be around 1.15 grams of magnesium malate in the morning, and 1.15 grams of magnesium malate in the evening, so you consume a total of 2.3 grams of magnesium malate powder per day, corresponding to around 350 mg of pure magnesium per day.
Ideally, one consumes around 350 to 500 mg of magnesium per day – the other magnesium comes from food.
Dose I take: around 1.15 gram of magnesium malate in the morning (after breakfast) and 1.15 gram of magnesium malate in the evening (before bed), which corresponds with around 2,300 mg of magnesium malate or 350 mg of pure magnesium.
HEALTH SUPPLEMENTS (VS LONGEVITY SUPPLEMENTS)
I introduced the notion of distinguising between “health supplements” and “longevity supplements”.
Longevity supplements (or “anti-aging” supplements) specifically slow down aging and extend lifespan, ideally maximum lifespan. Examples of such supplements are chondroitin, low-dose lithium, fisetin, alpha-ketoglutarate and so on.
Health supplements on the other hand do not really significantly slow down aging (they do not increase maximum lifespan), but they can shorten lifespan, or make you sick or feel bad when you are deficient in them.
Many health supplements are vitamins, minerals, and other micronutrients that are needed for proper functioning of our body, and thus for proper health, such as vitamin D, vitamin A, vitamin E, zinc, B vitamins, calcium, omega-3 fatty acids, and so on.
Deficiencies in them can shorten lifespan or increase your risk of vairous diseases and ailments. However, giving extra amounts of these substances (like giving extra amounts of vitamin E, omega-3s, etc) does not extend lifespan unfortunately.
I will discuss the most important health supplements almost everyone should take, whether you feel healthy or not, or whether your blood test is normal or not (blood tests are bad at tracking deficiencies of most micronutrients). The reasons for this we explained earlier, such as the fact that our body is not well made to take up all needed micronutrients properly – especially when we get older, that it’s very difficult via diet to take up all these micronutrients in optimal doses for longevity, that often the official dose recommendations are too low, and so on.
So let’s start!
High-quality omega-3 fatty acids
These fatty acids play a pivotal role in heart health, immune health and eye health. Most people are deficient in omega-3 fatty acids.
Sufficient intakes of omega-3 fatty acids also improves sleep and reduces dry skin (and dry eyes).
Therefore, I take at least 1,200 mg of EPA + DHA per day.
On top of taking a daily omega-3 fatty acid supplement I recommend consuming:
– At least 4-5 times per week fatty fish like salmon, mackerel, anchovy, or sardines. Some longevity hackers only consume fish (instead of meat).
– At least 4-5 times per week fish roe (e.g. herring roe, lumpfish roe or salmon roe). Fish roe are are eggs from fish which contain large amounts of phosphatidylcholine-omega-3 fatty acids, which can penetrate much better the blood-brain-barrier than omega-3s from fatty fish.
– At least one handful of walnuts, chia seed and/or flax seed every day. These contain vegetable omega-3s (however, these are much less well converted into animal based omega-3s like EPA and DHA found in fish and fish roe).
A B vitamin complex consists of multiple B vitamins, ideally all of them, like vitamin B1, vitamin B1, vitamin B1, vitamin B1, vitamin B1, vitamin B1, vitamin B1, vitamin B1.
B vitamins play many important roles in the body, especially in metabolism and neuronal and brain function. Given elderly people extra B vitamins could significantly reduce age-related brain shrinking (R,R), but only if enough different B vitamins are given.
Ideally, you take a B vitamin complex with higher doses of B vitamins than recommended by most governments (e.g. 200-300% of the recommended daily allowances – for some B vitamins even more).
Be careful however for vitamin B6: too high doses of vitamin B6 could in the long term cause nerve damage (neuropathy). Therefore, make sure your supplement does not contain more then 25 mg of vitamin B6.
A B supplement I take is Stress B-Complex by Thorne (not sponsored). It contains the same for of folate as found in nature (methyltetrahydrofolate) instead of the more “unnatural” folic acid form found in most supplements. I take 1/3rd of a capsule per day.
Choline is often called the “forgotten B vitamin”. Only quite recently governments realised that this is an important vitamin of which people should take more. Too little intake of choline (as is the case for most people in the west) causes DNA instability, double strand DNA breaks, metabolic problems (like fatty liver disease), liver cancer, reduced brain function and so on. In fact, choline is one of the very few nutrients that when animals are experimentally derived from it can rapidle cause (liver) cancer.
However, there are some studies hinting that choline could increase the risk of heart disease given some bacteria in the gut of some people could convert choline into TMAO, a substance that can cause vascular atherosclerosis.
However, other studies do not show an effect of increased choline intake. Also, specific foods like fish contain a lot of choline, but studies show that high fish intakes are associated with a reduced risk of atherosclerosis.
I take myself choline chloride instead of choline bitartrate. In some people, choline bitartrate can give gut and muscle problems, or cause fatigue (some scientists speculate that the bitartrate can foster an unhealthy microbiome in some people).
I take around 300 mg of choline per day.
Despite consuming yogurt and milk, many people are still calcium deficient. Also, I do not promote consuming animal milk, given this can accelerate aging (R,R,R,R)
Additionally, many people are intolerant for diary products like cheese or yoghurt (dairy contains many immunogenic proteins that trigger the immune system, in the gut or systemically).
However, calcium is important for your health. It is involved in neuronal and muscle conduction and calms the mind. it of course is needed for strong bones too.
Given I don’t consume dairy products, I consume 2×500 mg of calcium. Do not take more than 1200 mg in one go: this can cause too high calcium peaks in the blood, which can accelerate calcification of the arteries, especially if one is vitamin K deficient (see further down below).
But even if you consume dairy regularly, ideally, one still takes calcium supplements given a bit of cheese per day and a glass of milk does not bring on a lot of calcium.
Many people have a vitamin D deficiency. And this even despite being outside quite a lot during the summer (sunlight converts vitamin D in the skin into its active form). The problem is that in the US and in Europe, which are located relatively high above the equator, the sunlight falls indirectly on the surface, and is less able to stimulate vitamin D production in the skin.
Also, the older we become, the less able the skin is to convert vitamin D via sunlight.
Vitamin D is needed for many reactions in the human body. Low levels of vitamin D are associated with an increased risk of heart disease, (auto)immune diseases, bone problems, depression, and so on.
Giving people vitamin D decreases the risk of heart disease and auto-immune diseases and general mortality.
Actually, vitamin D and omega-3 fatty acids (and B vitamins) work synergistically. For example, a study showed that if elderly people take vitamin D, omega-3 fatty acids and regularly exercise, they reduce their risk of cancer by xx %.
Many governments advise a daily intake of around 400 International Units (IU) of vitamin D per day. However, many vitamin D experts and endocrinologists recommend much higher intakes of vitamin D, around 4000 to 5000 units per day.
I take 5000 units of vitamin D in the morning.
If you take vitamin D, you also need to combine it with vitamin K. These two vitamins work synergistically. Vitamin D for example enables the uptake of calcium from the gut, while vitamin K makes sure the calcium ends up in the bones and not blood vessel walls.
Vitamin K can also improve metabolism, including mitochondrial functioning (R). It could also reduce the risk of neurodegenerative diseases (R) and heart diseases (R).
There exist two forms of vitamin K: vitamin K1 and vitamin K2. Vitamin K2 is recommended. Make also sure it’s the right form of vitamin K2, ideally vitamin K4 (and some other forms of vitamin K2).
Also, make sure the dose of vitamin K2 is high enough (many supplements contain too low amounts of vitamin K2): at least 100 ug per day.
I take xxxx every morning.
Slowly build up the intake of iodine. Start with 100-150 micrograms (0.1-0.15 mg) of iodine per day, doubling the dose every two weeks until you reach around 1,000-1,200 micrograms (1 to 1.2 mg) per day.
Iodine drops are convenient in the beginning because one can easily dose these. If the daily dose becomes too high (requiring too many drops), one can switch to iodine pills.
If the pill contains too much iodine (e.g., 4 mg of iodine), get a pill cutter and cut the pill into (four) smaller parts.
Examples of iodine supplements are (not sponsored):
Iodine + iodide droplets: link
Iodine + iodide pills, 6.25 mg (cut into four to five pieces): link
When providing more iodine, the thyroid gland will start to work harder (again). Converting iodine into thyroid hormones generates lots of free radicals. To protect the thyroid gland against this increase in free radical production, take vitamin C, selenium and vitamin E:
- Vitamin C: 2 x 500 mg per day
- Selenium: 1 to 2 Brazil nuts per day, or 100 ug of selenium yeast (not selenium methionine) per day
- Take vitamin E via almonds, hazelnuts, and sunflower seeds (a few handfuls per day)
Potassium is a very important mineral for our body to function properly. The body needs large amounts of potassium on a daily basis. For example, potassium is needed to generate the membrane potential that keeps all our cells working; little pumps in our cell membranes continuously pump potassium inside and sodium outside our cells; it’s estimated that about 30% of our resting energy is just spent at generating energy (ATP) to keep these potassium-sodium pumps working.
Potassium is also needed in many other cellular processes, like xxx and yyy.
Unfortunately, most people in the west do not consume enough potassium, even when they eat healthily.
We see that adding extra potassium to the diet reduces mortality by xx (R,R,R).
So how can one increase potassium in the diet?
Firstly, start replacing your normal salt (sodium chloride) with a mixed salt that contains around 66% to 75% potassium chloride and the remainder containing sodium chloride (normal salt). Salts consisting of 100% potassium chloride tend to taste too bitter for most people.
Secondly, on top of replacing normal salt with potassium salt, one can also take a few grams of potassium chloride per day:
When using 100% potassium chloride:
- After breakfast, add 2,000 mg (2 grams) of potassium chloride in one jar of water or another drink.
- After dinner, add 2,000 mg (2 grams) of potassium chloride in one jar of water or another drink.
Given one gram of 100% potassium chloride contains 524 mg of potassium (and 476 mg of chloride), 2 x 2,000 mg of pure potassium chloride would correspond with 2,000 mg of potassium per day.
When using a mixed salt consisting of 66% potassium chloride and 33% sodium chloride (e.g. LoSalt):
- After breakfast, add 2,000 mg (2 grams) of this mixed salt in one jar of water or another drink.
- After lunch, add 2,000 mg (2 grams) of this mixed salt in one jar of water or another drink.
- After dinner, add 2,000 mg (2 grams) of this mixed salt in one jar of water or another drink.
5.8 grams of LoSalt contain 2,000 mg of potassium. Such a mixed salt would still bring on an extra 750 mg of sodium. To put this into perspective, most countries recommend a maximum intake of 2,300 mg of sodium which corresponds to 6 grams of sodium chloride (classic salt).
It’s important to always add the salt to a large amount of liquid given a too high concentration of potassium chloride can damage the lining of the esophagus or stomach (it’s a salt after all).
Online one can find various warnings that too much potassium is dangerous, often written by people who are not very knowledgeable about medicine. Potassium is very dangerous when injected intravenously (directly into the bloodstream). When taken orally, potassium is not dangerous when taken the amounts mentioned here. Only people with significant renal failure or other rare disorders that make it difficult for the body to get rid of potassium have to be careful with too much potassium.
Many studies show that extra potassium significantly reduces blood pressure, and that it reduces cardiovascular and all-cause mortality.
Vitamin A is an often underestimated vitamin. It’s however a vitamin many people are deficient in. Vitamin A is needed for proper vision and epithelial health. Epithelial cells are cells that line many surfaces in our body, like our skin, the cornea of the eye, gut, lung alveoli, and so on. Vitamin A is needed to keep the gut lining intact (together with vitamin D, zinc and iodine) which is important to prevent leaky gut syndrome, in which the gut epithelial cells cannot keep toxic, unhealthy substances inside the gut, so it leaks from the gut through the epithelial cells in the bloodstream where it can cause inflammation, amont other things.
Vitamin also can help with dry or itchy eyes, which is caused by damage to the epithelial cells that line the outside of the eye, such as the cornea.
There exist two main kinds of vitamin A: animal-derived vitamin A (retinoids) and plant-based vitamin A (carotenoids). For vitamin A to be active in our body, it needs to be converted in the animal-based retionoid form. Plants that look orange like pumpkins and carrots are rich sources of carotenoids, as are legumes like kale and broccoli. Many people believe that getting “vitamin A” from plants is sufficient to make sure they take in enough vitamin A. However, the body is quite bad in converting carotenoids from plants into retinoids, the active form. In fact, studies have shown that giving people huge amounts of carotenoids still does not increase levels of retinoids (R). So therefore, it’s recommended to take the animal-based, active form of vitamin A, namely the retinoid form, like retinyl-palmitate.
As mentioned before, many people do not consume sufficient amounts of animal-based vitamin A, especially in recent times. This was different a long time ago, when people still consumed lots of organ meat; including the liver which is very rich in vitamin A, including in prehistoric times. But even my grandfather regularly ate liver, a thing that people currently hardly do anymore. However, I prefer taking supplements of animal-based vitamin A instead of consuming an animal product like liver.
One has to be careful with taking too much vitamin A. Ideally, one takes around 2500 to maximum 5000 units of vitamin A, In fact, we see in studies that too much vitamin A, like 20 000 unites per day, can lead to problems with bone formation. One reason for this could be that too much vitamin A and too little vitamin D (both vitamins work synergistically) can lead to bone problems. Therefore, I would keep the amount of vitamin A on the lower end.
Vitamin C is a very well known vitamin. It’s often described as an antioxidant, but it has many other effects in the body. For example, vitamin C improves the epigenome and mitochondrial functioning.
I take vitamin C, 2×500 mg per day.
Iron deficiency is one of the most common deficiencies, especially in women.
Classical signs of too little iron are fatigue, difficulty concentrating, muscle aches. Sometimes people are asymptomatic. Also, sometimes people still can be iron deficient despite having normal iron blood levels (R).
However, iron can be a sword cutting at two sides: too little is not healthy and can significantly impair the quality of life, but too much iron causes a lot of oxidative stress, and could increase the risk of diseases like Parkinson’s disease or Alzheimer’s (R) (albeit that too little iron could also increase the risk of Parkinson’s disease (R)).
Therefore, I recommend supplementing with low levels of iron, like around 15 to 20 mg or iron per day. This is way lower than amounts that medical doctors sometimes give to treat iron deficiency, like 80 to 200 mg of iron per day. Such high doses are not recommended, given they can cause significant oxidative stress.
Always combine iron supplements with vitamin C. Vitamin C improves the uptake of iron, and also reduces the oxidative stress in the body.
Zinc is an often forgotten mineral. It however plays important roles in the immune system, skin health and brain health.
I take 15 mg per day of zinc, unless your multivitamin contains a dose similar to this. It’s however important not to take too much zinc (e.g. 40-50 mg per day), given it can cause too much oxidation, and hinder the absorption of other minerals, like copper.
“Should I take a multivitamin?” is a question I have heard a gazillion times. Many doctors have strong opinions about multivitamins: some of them find them them completely useless while others are big proponents of a daily multivitamin. As I will explain here, it’s a complex story.
Firstly, let me start with the main shortcomings of multivitamins and then I’ll tell you why taking one is still ok, on the condition you incorporate it in the right way.
Multivitamins have many shortcomings; such as the following:
[INSERT FROM SOCIAL MEDIA DOC]
This also explains why most multivitamins do not work in clinical studies; they are incomplete (not using all vitamins and minerals and other micronutrients), use the wrong forms, do not last long enough and so on.
So how to solve this? Firstly, one can take a multivitamin to cover the main micronutrients that are delivered in most multivitamins in the right dose and form, like manganese, molybdenum, and so on. Sometimes they also contain enough iron and zinc and cupper, so you don’t have to take these separately.
However, given multivitamins contain too low doses of many other minerals, vitamins and other micronutrients, one need to take these on top of the multivitamin. So taking them separately; these are micronutrients like vitamin D (around 4000 to 5000 units – most multivitamins only contain 400 units), around 350 to 500 mg of magnesium (most multivitamins only contain 50 mg of magnesium), around 800 to 1000 mg of calcium per day (most multivitamins contain only 50 to 100 mg), potassium at least 2000 mg extra per day (most multivitamins only contain 50 to 100 mg), a B vitamin complex (which contains several times the daily recommended amount of B vitamins).
As discussed earlier, taking extra amounts of a specific micronutrient as a supplement still won’t cut it for some ingredients given it’s almost impossible to find the right form as a supplement. This is specifically the case for vitamin E. Most vitamin E in supplement forms is a synthetic or semi-synthetic form. In many supplements vitamin E is in the artificial alpha-tocopherol acetate or succinate form; alpha-tocopherol succinate is even a pro-oxidative substance instead of an antioxidant.
Also, in nature various different forms of vitamin E exist, while most supplements contain only one form. There are some supplements that offer multiple different forms of natural vitamin E (supplements containing tocopherols and tocotrienols), but these still often do not contain all 8 forms of vitamin E found in nature, and often contain why too high doses of vitamin E, like 300 to 400 mg while the recommended amount of vitamin E is around 15 mg.
So the best way to get vitamin E is by consuming vitamin E-rich foods on a daily basis, like almonds, hazelnuts and sunflower seeds. One can add other “vitamin E rich foods” like avocado or green leafy vegetables, but these already contain much less vitamin E than the nuts and seeds I just mentioned. We talk more about this in the section about “vitamin E” below.
It’s estimated that about 90 (?) percent of people do not reach their daily required intakes of vitamin E.
This is not surprising, given most foods contain little vitamin E, and there are only a few foods with “high” levels of vitamin E, but even then one still has to consume quite large amounts of these foods.
Another problem is that most vitamin E in supplements is artificial, semi-artificial, too oxidized or consists of only one form (alpha-tocopherol) and not the 7 other forms of vitamin E found in nature.
For example, lots of supplements contain “vitamin E” as artificial alpha-tocopherol acetate or alpha-tocopherol succinate. However, alpha-tocopherol succinate is not an antioxidant, it actually has pro-oxidant activities (R)!
Therefore, I take vitamin E not via supplements, but via specific foods. I consume around 3 handfuls of sunflower seeds, almonds and/or hazelnuts every day. These foods contain high amounts of vitamin E.
I also consume lots of green leafy vegetables each day, and regularly avocado. But even when consuming these foods, it’s difficult to take in sufficiently high amounts of vitamin E.