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.
Longevity supplements versus health supplements
While many people have a significant interest in longevity supplements, health supplements are also important.
Health supplements contain micronutrients many people are deficient in, even if they eat “healthy”. Some important reasons for this 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).
In other words, 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 undermine your health and increase your risk of many diseases.
So what are the best longevity and health supplements?
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.
Put differently, 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:
LONGEVITY (ANTI-AGING) SUPPLEMENTS
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.
Lithium has been shown to indeed extend lifespan and slow aging in various species (R,R,R,R,R,R).
In humans, lithium intake has been associated with reduced mortality (R,R,R), reduced risk of neurodegenerative diseases like Alzheimer’s (R,R,R) and reduced suicide (R,R).
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).
Lithium, longevity and aging
Lithium positively impacts many fundamental aging mechanisms.
For example, lithium has epigenetic effects, enabling the upregulation of genes that produce healthy proteins, like brain-derived neurotrophic factor (BDNF) (R,R).
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.
In fact, we actually see that low doses of lithium can protect the kidneys against damage and aging (R,R).
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).
Chondroitin, longevity and 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
Glucosamine has been shown to extend lifespan in different organisms (R,R,R).
In humans, glucosamine was one of the very few supplements associated with reduced mortality (R,R).
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).
People who take glucosamine supplements have less risk of various cancers, such as colorectal cancer (R) and lung cancer (R), especially in combination with chondroitin.
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.
Glucosamine, longevity and aging
Many studies in rodents show that glucosamine reduces inflammation (R), including the inflammation that happens in the blood vessel walls which contributes to atherosclerosis (R).
Glucosamine use in humans has been associated with lower proinflammatory proteins in the blood (such as C-reactive protein) (R,R).
Glucosamine also can improve blood vessel health (R). In humans, glucosamine improves the vascular endothelium, which are the cells that line our blood vessels (R).
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.
For example, fisetin is a powerful inhibitor of inflammation (R,R). This is important, given that during aging low-grade inflammation starts to occur everywhere in our body (called “inflammaging”).
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).
Fisetin also has epigenetic effects and can improve metabolism, for example by activating sirtuins (R,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).
In humans, we see that fisetin reduces inflammation (R) and improves the outcome of stroke (R). According to the researchers:
“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.
Unfortunately, during aging, levels of NAD+ in our cells decline (R,R).
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 humans, alpha-ketoglutarate can protect organs during physiological stress, as during operations (R,R,R,R,R,R) or dialysis (R,R,R,R).
Alpha-ketoglutarate also plays a role in collagen synthesis and bone health. It could also slow down osteoporosis in humans (R,R).
In some preliminary human studies, alpha-ketoglutarate could rejuvenate humans, measured via epigenetic clocks (R).
Alpha-ketoglutarate, longevity and 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.
Glycine has been shown to extend lifespan in multiple species (R,R,R,R,R).
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).
Higher levels of glycine have been associated with a reduced risk of a heart attack in humans (R) and a healthier metabolism (R,R,R,R).
Glycine could also help protect the brain against stroke damage (R), and could improve memory (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).
Does oral hyaluronic acid reduce wrinkles and joint problems?
Most people will know hyaluronic acid as an ingredient in skin creams or serums to reduce wrinkles (as I also discuss in the article about best anti-aging skin products). 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).
Given hyaluronic acid is also part of the cartilage and ligaments forming our joints, it can also improve osteoarthritis of our joints, like in the knee (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.
HEALTH SUPPLEMENTS (VS LONGEVITY SUPPLEMENTS)
We earlier discussed the importance of distinguishing 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 “suboptimal” when you are deficient in them.
Many health supplements are vitamins, minerals, and other micronutrients needed for the 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.
Why health supplements matter
Deficiencies in health supplements can shorten lifespan or increase the risk of various diseases and ailments. However, taking extra amounts of these substances (like giving high amounts of vitamin E, omega-3s, etc) does not extend lifespan unfortunately.
Nonetheless, they are very important. All too often I see people who take the latest and most promising anti-aging supplements and drugs, like rapamycin, metformin, alpha-ketoglutarate, microdosed lithium, and so on, while showing overt signs of iodine deficiency (such as having a puffy face and a slow metabolism), iron, vitamin A and zinc deficiency (e.g. pale skin, premature baldness), omega-3 deficiency (dry, coarse skin and a tendency for depression), and so on.
It would be very unfortunate for one to take longevity supplements while being deficient in basic vitamins and minerals. Deficiencies of such micronutrients increases the risk of cancer, Alzheimer’s disease, atherosclerosis, brain atrophy, accelerated aging and many other problems, especially in the long term.
For example, B vitamins (including choline) are needed for proper DNA synthesis and to significantly reduce DNA mutations and even DNA double strand breaks. They also play important roles in epigenetic regulation and energy production.
So you can take all the metformin in the world, but if you still have lots of DNA damage and improper epigenetic regulation you still could get cancer in your sixties and die from it.
Why health suppements (e.g. vitamins and minerals) are underestimated
It never ceases me to amaze me how people tend to underestimate the importance of health supplements. One important reason for this is that people, including doctors, are not very knowledgeable about this important subject. It’s hardly taught in most medical curriculums.
Due to the lack of knowledge regarding the importance of vitamins and minerals for the body (e.g. their involvement in many important biochemical pathways) and the consequences of their deficiencies (e.g. an increased risk of atherosclerosis when one is deficient in iodine, or an increased risk of brain atrophy when being deficient in B vitamins), supplementation tends to be brushed aside.
However, the classical definition of a vitamin is that of being a substance that the body needs and without it would become very sick and die.
Another reason for the widespread negligence of vitamins and minerals for our health are the official government recommendations. They keep spreading the oversimplification that if you “eat a healthy and varied diet, you don’t need supplements”.
As I discussed earlier, this is not the case. Even if you eat healthily, it’s very difficult to get for example sufficient amounts of iodine or vitamin D or magnesium, especially when you are older and for a long, healthy life.
Also, many studies the government bases itself on are very old or look at very crude biomarkers of disease (e.g. overt anemia for vitamin B12 deficiency, but not at DNA double strand breaks for example), so you often need higher levels to also prevent these much more difficult to detect problems that arise from deficiencies. And importantly, almost no one eats an optimal, healthy, varied longevity diet anyhow.
To make a long story short, we should not underestimate the importance of making sure one takes the right amount of vitamins and minerals, and this for their whole life.
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), or whether you eat “healthy” or not.
1. High-quality omega-3 fatty acids
Omega-3 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).
There exist vegetable sources of omega-3s, such as walnuts, chia seed and flax seed. However, only a very small fraction of these vegetable omega-3s are converted in their active forms, namely EPA and DHA.
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 eggs from fish which contain large amounts of phosphatidylcholine-omega-3 fatty acids, which can penetrate far better the blood-brain-barrier compared to 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).
2. B-vitamin complex
A B vitamin complex consists of many different B vitamins, such as vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B9 and vitamin B12.
B vitamins play many important roles in the body, especially for our metabolism, and nerve and brain function. Giving elderly people extra B vitamins could significantly reduce age-related brain shrinking, but only if enough different forms of B vitamins are given (some studies only provide two B vitamins, like vitamin B6 and B12, instead of using a B vitamin complex).
Ideally, you take a B vitamin complex with higher doses of B vitamins than recommended by 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 than 25 mg of vitamin B6.
A B supplement I take is Stress B-Complex by Thorne (not sponsored). It contains the same form of folate as found in nature (methyltetrahydrofolate) instead of the more “unnatural” and more difficult to metabolize folic acid-form found in most B vitamin supplements. I take 1/3rd of a capsule per day (I open the capsule and pour roughly one third of the powder in a glass of water and then close the capsule).
Choline is often called the “forgotten B vitamin”.
Only quite recently some governments realized that choline is an important vitamin, and of which people should take more.
Too little intake of choline (as is the case for most people in the west) causes DNA damage (R,R,R), double strand DNA breaks (R), mitochondrial defects (R), metabolic problems (like fatty liver disease), liver cancer, reduced brain function, and many others. In fact, choline is one of the very few nutrients that when animals are experimentally derived from it can rapidle cause a fatty liver, and (liver) cancer.
Choline is also needed for proper epigenetic maintenance, and for brain function For example, choline is a component of acetylcholine, which is an important neurotransmitter in the brain, and is also a component of phosphatidylcholine, which are fats that make up our brain cell membranes.
Although choline is very important for proper functioning of our body, there are some studies hinting that choline could increase the risk of heart disease. Specific species of bacteria in the gut of some people could convert choline into TMAO (trimethylamine oxide), a substance that can cause vascular atherosclerosis.
However, other studies do not show an association with increased choline intake and heart disease. Additionally, specific heart-healthy foods like fish contain a lot of choline and studies show that high fish intakes are actually associated with a reduced risk of heart disease.
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 the growth of an unhealthy microbiome in some people).
I take around 300 mg of extra choline per day (besides eating fish 4-5 times per week, and a few eggs per week). I take choline chloride (for example this brand – not sponsored) instead of choline bitartrate because the bitartrate form of choline makes me very tired when I take it. I take 15 drops in the morning and 15 drops in the evening of this brand, corresponding to about 490 mg of choline per day.
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. Furthermore, magnesium is 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).
Giving people magnesium improves vascular function (R). A higher magnesium intake has been associated with less risk of heart disease (R,R,R). Magnesium can also improve metabolism in humans (R,R,R,R,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 very 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.
Which form of magnesium is best?
Most supplements use the magnesium oxide form. This is not an ideal form. Firstly, magnesium oxide has significant laxative effects. In fact, in earlier times magnesium oxide was used 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 been 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 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 (to make things even more complicated, magnesium can provide more energy but can also help to relax).
By taking magnesium malate or magnesium glycinate instead of magnesium oxide, you hit two healthy 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.
This is because 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.
In the table below you can see each magnesium compound and how much of the weight of the molecule is actually magnesium:
|Magnesium salt||Percentage magnesium|
Given you need more than two grams of these magnesium compounds per day, it’s difficult to put all this powder in a pill. Also, most “magnesium supplements” contain only little amounts of pure magnesium.
Therefore, it’s best to take magnesium as a powder instead of in pill form, for example magnesium malate powder or magnesium glycinate powder. You can buy a little weighing scale (with an accuracy up to 0.01 gram) like these ones (not sponsored) to weigh the proper amount of powder you need.
This 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.
Ideally, one consumes around 350 to 500 mg of magnesium per day – the other magnesium can come 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 to around 2,300 mg of magnesium malate or 350 mg of pure magnesium per day.
Despite consuming yogurt and milk, many people do not get enough calcium.
It’s even more difficult to get enough calcium when not consuming milk. However, not consuming milk is actually something that I advise, given animal milk accelerates aging in many ways (milk is a strong activator of canonical pro-aging pathways like mTOR, IGF and insulin (R,R,R,R), contains pro-aging substances like galactose (R,R,,R,), and has been associated with increased mortality in humans by independent, non-dairy funded, long-term studies (R)).
Another problem with milk, and dairy products in general, is that it can cause allergies, intolerances, and has immunogenic properties that can trigger the immune system and inflammation, in the gut or systemically.
However, calcium is important for health. It is involved in neuronal and muscle conduction and proper brain function. It also helps to calm nerves and the mind. And of course it is needed for strong bones too.
Given I don’t consume dairy products, I take calcium supplements. I consume 2 x 500 mg of calcium per day. 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 still consume yogurt and cheese regularly, often these foods are not sufficient to get all the calcium you need (so supplements are still advised). Cheese and yogurt are better (healthier) than milk, but still many people are somewhat – knowingly or unknowingly- intolerant of cheese (e.g. causing leaky gut, brain fog, allergies, eczema, asthma, tiredness, producing more mucus in the throat, worsening gastric reflux, and so on).
And instead of animal-based yogurt, I would opt for plant-based, low-sugar yogurt, like soy yogurt, almond yogurt or coconut yogurt.
6. Vitamin D
Many people have a vitamin D deficiency. This even despite being outside a lot during the summer; sunlight converts vitamin D in the skin into its active form.
The problem is that the US and Europe are located relatively high above the equator, so the sunlight falls indirectly on the earth’s surface, making the sun rays less powerful and less able to induce vitamin D production in the skin.
Also, the older we become, the less able the skin is to create vitamin D via sunlight.
Vitamin D is needed for many things in the human body. Vitamin D regulates hundreds of genes and 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, auto-immune diseases, and 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 no less than 61% (R).
Many governments advise a daily intake of only 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, from this brand (not sponsored).
7. Vitamin K
If you take vitamin D, you need to combine it with vitamin K. These two vitamins work synergistically.
For example, vitamin D increases 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 also improves metabolism, including mitochondrial functioning (R,R). It could also reduce the risk of neurodegenerative diseases (R) and heart diseases (R).
According to Dr. Samir Kapadia from the Cleveland Clinic in the USA and Dr. Essa Hariri from Maastricht University in the Netherlands:
“There is an alarmingly high prevalence of vitamin K deficiency and suboptimal recommended intake among the general population in the USA. A growing body of evidence supports the potential role of vitamin K2 in cardiovascular health. Vitamin K2 helps regulate the homeostasis of soft tissue calcification through activation of an anti-calcific protein known as matrix Gla protein (MGP). Studies demonstrate a strong association between vitamin K deficiency, as assessed by plasma inactive MGP, and arterial stiffness, vascular and valvular calcification, heart failure and cardiovascular mortality. Increased vitamin K2 intake may reduce arterial stiffness, slow progression of vascular and valvular calcification, lower the incidence of diabetes and coronary artery disease, and decrease cardiovascular mortality. Further efforts are necessary to establish vitamin K2 as a safe, cost-effective, and efficacious supplement for preventing and improving cardiovascular outcomes.”
Which form of vitamin K2 is best? MK-4 versus MK-7
There are two main forms of vitamin K: vitamin K1 (phylloquinone) and vitamin K2 (menaquinone).
Vitamin K2 is recommended over vitamin K1.
Vitamin K1 is found in plants (e.g. green leafy vegetables) and can be converted in the gut by bacteria into the bioactive form, vitamin K2. More specifically, vitamin K1 is converted by bacteria into a specific form of vitamin K2, namely menaquinone 7 (MK-7).
However, there exists different forms of vitamin K2, such as menaquinone 7 (MK-7) and menaquinone 4 (MK-4), and others.
Our bodies can make MK-4 from vitamin K1 (but only in very low quantities). However, our bodies cannot make MK-7. Bacteria (like some species found in our gut) can convert vitamin K1 into MK-7.
MK-4 is especially good in reducing the risk of bone fractures, as has been shown in multiple clinical trials in humans. A meta-analysis of different clinical trials showed that already 45 mg of MK-4 could decrease hip fractures by 73%, vertebral fractures by 60%,and non-vertebral fractures (e.g. wrist, ribs, etc) by 81%.
MK-7 on the other hand has been associated with reduced inflammation and lower cardiovascular risk (for example by reducing vascular calcification).
Vitamin MK-7 is also found in high levels in natto, which are fermented soy beans and is a Japanese delicacy.
Studies show that at least half of people in the west are deficient in vitamin K2 (as measured by undercarboxylated osteocalcin; given this biomarker is not perfect, likely this percentage is an underestimation).
When taking supplements, make sure you take the proper forms of vitamin K2, ideally a combination of vitamin MK-4 and MK-7.
Also, keep in mind there is the natural form of MK-7, the “trans form”, while there is also the synthetic, “unnatural” form of MK-7, called the “cis form”. Many supplements contain both the cis and trans form, which is not ideal: it’s better to take a supplement containing only the natural trans form of MK-7.
Also, make sure the dose of vitamin K2 is high enough (many supplements contain too low amounts of vitamin K2): at least 45 ug of vitamin MK-4 and 100 ug of vitamin MK-7 per day.
Note: if you take anticoagulation medication, such as warfarin, you should be careful with taking vitamin K supplements. Anticoagulants like warfarin inhibit the function of vitamin K, to make the blood less coagulable. But don’t worry, taking vitamin K2 supplements in the doses advised here doesn’t cause coagulation (in fact, many studies show that higher levels of vitamin K2 are associated with reduced heart disease). However, anticoagulants like warfarin impeding vitamin K2 function can cause significant side-effects, like too much arterial calcification (because vitamin K2 promotes the uptake of calcium into the bones and not into the artery walls).
An example of a vitamin K supplement containing the correct two different forms of vitamin K2 in high enough doses is Super K from Life Extension (not sponsored).
Iodine deficiency is very common. Studies estimate that at least 70% of people do not consume enough iodine, but likely this number is higher.
In fact, unless you eat seaweed regularly, chances are very, very high you are iodine deficient, because you hardly find iodine in any foods (by the way, seaweed consumption, via seaweed or kelp supplements, is also not advised because the amounts of iodine in seaweed or kelp supplements can be too high or fluctuate too much, despite what the labels says).
The reason why most people are iodine deficient is because iodine is so little found in foods. Eggs contain a little bit of iodine. And fish. But these levels are too low. Bread contains iodine because it has been added to it. In fact, given iodine deficiency was such a severe health problem in the past, governments made it mandatory to add iodine to bread and salt. However, often bread contains too little iodine, especially in amounts needed for optimal health and longevity. And iodine in salt evaporates quickly after the salt jar has been opened. Also, an increasing number of bakers are replacing iodine in bread with bromide (at least in countries like the US – other countries, like the UK, banned this practice), leading to even more iodine deficiency (also because bromide counteracts iodine in the body).
To make things worse, salt and bread should be consumed less, given too much salt and bread are not that healthy, which however could aggravate iodine deficiency even more.
In fact, iodine deficiency has been a problem for tens of thousands of years for our species. Diseases caused by too little iodine, like goiter, hypothyroidism and severe mental retardation in children were very prevalent.
Iodine in health, disease and longevity
Iodine is needed for proper function of the thyroid gland, which is a master regulator of our metabolism. The thyroid gland produces thyroid hormones (which contain iodine). These hormones travel to every cell in our body, and regulate gene expression and impact cell metabolism, growth and innumerable other mechanisms.
Iodine is also needed for brain development and brain function. Before governments put iodine into bread and salt, many children were born with severe mental retardation, called “cretinism”.
Given the importance of iodine in brain development, some scientists believe that even mild, subclinical deficiencies of iodine during pregnancy and childhood can still lead to suboptimal brain maturation, which translates in a somewhat lower IQ or more risk of AD(H)D (R,R) (these things are however very difficult to research, especially given it’s difficult to even properly measure iodine deficiency in the first place – as I will discuss later on).
Deficiencies in iodine can lead to a slow thyroid gland (hypothyroidism), a very common problem – but can also in some cases lead to a too fast thyroid gland, called hyperthyroidism.
However, too little iodine is also thought to play a role in many cancers such as stomach cancer, breast cancer, and prostate cancer, as many studies in humans suggest (R,R). And depriving rodents from iodine increases their risk of cancer, while giving cancer-prone rats iodine cuts down their cancer rate by half (R).
That iodine could play a role in breast cancer should not come as a real surprise, given that the second largest supply of iodine in the body (after the thyroid gland) is female breast tissue – likely to make sure a newborn child gets enough iodine for proper brain development, among other things. Also, a classical sign of iodine deficiency are lumps in the breast, called fibrocystic breast disease (FBD), which can be remedied by taking high levels of iodine.
The role of iodine in stomach cancer could also make sense for several reasons, one being that stomach cells concentrate iodine in order to protect themselves against damage.
Too little iodine can also increase the risk of atherosclerosis (R). Old studies done with rodents showed that putting these animals on an iodine-deficient diet causes massive atherosclerosis. And giving them iodine while putting them on an unhealthy, atherosclerosis-promoting diet protects them against heart disease.
Why it is so difficult to measure iodine deficiency
Despite that iodine deficiency is very prevalent, it’s underdiagnosed in many people. One reason for this is that it’s difficult to properly measure iodine deficiency.
Mostly, TSH (thyroid stimulating hormone) levels are measured via a blood draw. However, TSH levels are a crude measurement of iodine deficiency or thyroid problems.
Furthermore, TSH levels can fluctuate widely during the day.
So a normal TSH level doesn’t mean your thyroid gland is spick and spam. Furthermore, even if your TSH levels would have been accurately measured, the cut-off values are likely not optimal. Most labs will state that TSH levels above 4 uIU//ml is a sign of a slow thyroid gland, while many endocrinologists claim that actually TSH levels above 2 uIU//ml can already be a sign of hypothyroidism.
A better test to detect iodine deficiency is an iodine challenge test. In this test, a large dose of iodine is given, and then iodine secretion in urine is measured over 24 hours. But even this test is not perfect (and only very few doctors have even ever heard of this test).
How much iodine should I take? How to take iodine supplements properly?
Most governments recommend taking 150 to 200 ug (microgram) per day of iodine.
However, these values are mainly based on avoiding serious problems stemming from too little iodine, like goiter, which is an enlarged thyroid gland mostly caused by iodine deficiency.
Some medical doctors believe much larger doses of iodine are needed for optimal health, up to even several milligrams per day (so thousands of micrograms per day). They claim that these values are not that far-fetched, given for example there are regions in Japan where people consume on average 2,000 to 3,000 ug (2 to 3 mg) of iodine per day.
I would recommend taking at least a few times the minimum amount that many governments advise (150 ug/day), so around 300 to 450 ug per day.
However, it’s important to slowly build up your intake of iodine.
Start with 100-150 micrograms (0.1-0.15 mg) of iodine per day, doubling the dose every three weeks until you reach around 300 to 450 micrograms 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), you can switch to iodine pills.
If the pill contains too much iodine (e.g., 1 mg of iodine), get a pill cutter and cut the pill into smaller parts.
Examples of iodine supplements are (not sponsored): Iodine + iodide droplets: link
Importantly: when starting to take more iodine, the thyroid gland will start to work harder. After all, the thyroid gland will produce more thyroid hormone, but a side effect of this process is the production of lot’s of free radicals.
These free radicals can damage the thyroid gland. In fact, this process is one of the reasons why the thyroid gland (and other glandular tissues) are generally so prone to auto-immune diseases.
Glandular tissues have to produce lots of substances, and as a side-effect of this production process also lots of free radicals are produced, which damage the glandular cells.
Given their close proximity to blood vessels (glandular cells need to secrete hormones or other substances into the blood), these cells come easily in contact with circulating white blood cells. The white blood cells notice and attack these damaged “unnatural” cells, which leads to an immune reaction, further damaging the cells.
For example, antibodies are produced against the thyroid gland, such as thyroid peroxidase (TPO) antibodies, thyroglobulin antibodies, or TSH receptor antibodies. This can lead to auto-immune diseases, like Hashimoto’s disease (a too slow thyroid gland) or Grave’s disease (a too fast thyroid gland because the antibodies latch onto receptors on the thyroid cells that activate the thyroid cells).
To complicate things more, too little iodine can lead to malfunction of the thyroid gland, which can also lead to damage to the thyroid gland, prompting the production of antibodies against the thyroid.
Some people have increased thyroid peroxidase (TPO) antibodies while having normal TSH levels. Many doctors will say there is no problem given “TSH levels are normal”. However, increased TPO antibodies are often a sign of an improper functioning thyroid gland, often due to years or decades of iodine deficiency.
Anyhow, to protect the thyroid gland against an increase in free radical production when suddenly extra iodine is taken, it’s important to take extra vitamin C, selenium and vitamin E, which can neutralize this free radical production:
- 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 one of those minerals many people, including medical doctors, tend to ignore.
That’s not a good thing because potassium is crucial for optimal health and longevity. Our body needs large amounts of potassium on a daily basis.
In fact, potassium is one of the main sustainers of life. Potassium is needed to generate the membrane potential that keeps all our cells working and alive. Little pumps in our cell membranes continuously pump potassium inside our cells and shuttle sodium outside our cells.
These pumps make it possible that cells contain about 30 times more potassium inside than outside (and about 10 times more sodium outside our cells than inside). This “membrane” potential sustains life.
For example, neurons can fire and heart cells contract because in less than a few milliseconds suddenly large amounts of sodium flow into the cells (sticking to and activating many proteins), while large amounts of potassium flow outside the cells. A few milliseconds later, this membrane potential is restored again when sodium is pumped out and potassium is pumped into the cells.
This influx of sodium atoms leads to important changes in the cell. For example, sodium atoms, which are positively charged, will stick to more negatively charged regions of proteins which then change shape, enabling them to perform their function (for example, membrane channels open up to let specific substances inside the cell).
It’s estimated that about 30% of our energy expenditure in rest is spent on generating energy (ATP) to keep these little sodium-potassium pumps working (!).
As I explained earlier when talking about our cellular power plants, the mitochondria, ATP is a molecule that can also stick or interact with proteins to change their shape, enabling them to perform their function. ATP briefly sticks to the sodium-potassium pumps helping them to pump sodium into and potassium out of the cells.
In fact, one of the main purposes of our mitochondria is to use the oxygen we breathe and the food we eat to create ATP to keep these sodium-potassium pumps working.
The most common way we die is because of lack of oxygen (for example, when one has a heart attack, the blood flow that transports oxygen to tissues stops). This lack of oxygen brings the mitochondria in a dire situation given that mitochondria need oxygen to produce ATP. Huge amounts of ATP are needed every millisecond to keep our sodium-potassium pumps working. So when there is no ATP made due to lack of oxygen, this leads to a massive influx of sodium into the cells and a potassium efflux outside our cells, which is not restored again (pumping sodium out an potassium back in), causing an “equilibrium” over the cell membranes, which causes the cells to malfunction and to die.
Potassium is needed in many cellular processes. Potassium is an important part of the electric signal that makes neurons and brain cells fire, muscle and heart cells contract, and that enables the functioning of important proteins (such as pyruvate kinase, an important enzyme involved in carbohydrate metabolism).
Unfortunately, most people in the west do not consume enough potassium.
Despite many “experts” claiming that increasing potassium intake is not really necessary (see further down), we see that adding even small amounts of potassium to the diet significantly reduces disease and mortality.
For example, a study with more than 10,000 participants found that for each 1,000 mg of extra potassium intake, the risk of heart disease was reduced by an impressive 18% (R).
Another study with 20,000 people showed that replacing normal salt (sodium chloride) with only a small amount of potassium salt (potassium chloride) reduced cardiovascular events by 13%, stroke by 14%, and mortality by 12% (R). Likely, if one would have replaced even more normal salt with potassium salt these results would be even more impressive.
These and many other studies hint that potassium especially has a big impact on improving blood vessel health, mainly by reducing hypertension (high blood pressure), which leads to less cardiovascular disease, and especially to a reduced risk of strokes (R).
Misconceptions about potassium deficiency
Despite the clear benefits of extra potassium intake, one can often read online, including even on health websites from prestigious medical institutes or universities, that one does not really have to worry about potassium given that “potassium deficiency is rare”.
A popular argument for this is that potassium “is found in many foods”, so it’s assumed that people get enough of this mineral. But that’s not the case. The FDA clearly warns that most people do not consume enough potassium. People in the west on average consume around 2,500 mg of potassium per day. The FDA recommends taking at least 4,700 mg per day (the “daily value” of potassium).
However, likely this amount should be even higher for optimal health and longevity. For example, looking at prehistoric times (when we were hunters-gatherers), people likely consumed around 7,000 to 15,000 mg (7 to 15 grams) of potassium per day (!) (R).
Furthermore, many clinical trials show that even adding a little bit of extra potassium to people’s diet, as in the form of potassium salt (potassium chloride), leads to a significant reduction of heart disease, stroke and mortality. Clearly, most people do not consume potassium for an optimal, long life.
Another main reason why many people still claim that potassium deficiency is “rare”, is that most people have normal potassium levels in the blood.
The problem however is that one can be deficient in potassium despite having “normal” blood potassium levels. Blood potassium levels don’t change easily, and also don’t say a lot about potassium levels in different tissues other than blood.
Blood potassium levels often become only abnormal when you have (very) serious problems, like kidney failure, severe dehydration, badly controlled diabetes, severe diarrhea, excessive sweating, or take specific medications (such as ACE inhibitors, angiotensin II receptor blockers, or taking lots of laxatives).
So measuring potassium levels in the blood is not a good method to “diagnose” potassium deficiency. Given blood potassium levels are normal in most people, it’s often erroneously assumed that potassium deficiency is a rare thing.
Does too much potassium cause heart problems?
Online one can find many warnings that too much potassium is very dangerous. It’s claimed that too much potassium can cause heart problems, like heart rhythm disorders and even cardiac arrest and death.
Unfortunately, this kind of wrong advice is often bandied about by people who are not very knowledgeable about medicine.
They base themselves on studies showing that injecting potassium can lead to severe heart rhythm disorders and cardiac arrest. In fact, potassium is one of the substances in lethal injections used for capital punishment. The high amount of potassium injected into the body causes massive cardiac arrest (remember that potassium leaving cells – and being pumped back into cells quickly again allows nervous cells to send signals and muscle cells to contract – a sudden high peak of potassium disrupts this process).
Potassium is indeed very dangerous when injected intravenously (directly into the bloodstream). But when taken orally, potassium is not dangerous, especially when taken the amounts mentioned here. When you take potassium orally, it’s slowly absorbed from the gut in the bloodstream. So there is no dangerous, sudden huge peak of potassium in the body as is the case with an injection.
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 when taken orally. But this is not the case for most people.
Many studies actually show that extra potassium intake reduces blood pressure, and cardiovascular and all-cause mortality.
Another reason why many self-proclaimed health experts still believe that too much potassium is dangerous is that they heard that the FDA has strict guidelines on potassium supplements.
Manufacturers of potassium supplements can only put 99 mg of potassium in their capsules (which is very little, knowing people need to ideally consume at least 4,700 mg of potassium per day). Many people concluded that this is because too much potassium can cause heart problems, kidney problems, and so on.
But this is not why the FDA has restricted the amount of potassium in capsules. The main reason is that when a capsule with too much potassium bursts open in the gut, it can damage the gut lining (causing burns). Potassium is a salt after all, and when a too large capsule bursts open in your gut it could locally cause too much damage. That’s why the FDA has restricted the amount of potassium in capsules.
Therefore, it’s better to take potassium as a powder, instead in capsule form, and dissolve this powder in a sufficiently large glass of fluid, so the potassium is diluted.
Potassium versus sodium in heart disease and hypertension
For decades, the medical field has overly concentrated on sodium to reduce hypertension and heart disease.
Innumerable people with heart disease and hypertension have been put on severe sodium-restriction diets, often with quite disappointing results.
This is because sodium is only a piece of the hypertension puzzle. Potassium plays an important role too.
Too much sodium indeed can cause hypertension (and other problems, like inflammation (R)), but only restricting sodium intake is an oversimplification.
Besides restricting sodium (but not too much, as I’ll discuss in a moment), one should also make sure people consume (much) more potassium. After all, potassium reduces hypertension. In fact, potassium and sodium work together to keep your blood pressure in balance.
The problem with our western diets is that they contain too much sodium and too little potassium. Manufacturers add lots of sodium to their foods to make them taste better, especially to soups, pizza’s, bread, sandwiches, tacos, savory snacks, cold cuts, chicken, canned foods (such as canned fish or legumes), and so on. So try to avoid these foods, or read the labels carefully to check sodium levels.
So while the amount of sodium in our diet has drastically increased, the amount of potassium has drastically decreased. This makes sense, given potassium is mainly found in healthy foods, of which many people started to eat less and less, such as vegetables, fruits and legumes.
However, some scientists believe that medicine has been focusing too much on reducing sodium intake, ignoring potassium intake. Some believe that reducing sodium intake too much can be unhealthy too, given sodium, just like potassium, has many important functions in the body (for example, helping our nerves and muscle cells to fire).
And indeed, more and more studies suggest that restricting sodium too much could actually increase the risk of a heart attack (R,R,R,R) (despite sometimes indeed reducing hypertension).
Restricting sodium too much could also increase the risk of insulin resistance for example (R,R,R,R).
How to get more potassium
So how can you increase your potassium intake?
Of course, the most important thing is to increase the amount of potassium-rich foods in your diet. These are not coincidentally foods that are also healthy, such as vegetables, fruits, legumes and nuts.
Another great way to increase potassium intake is by replacing your normal salt (sodium chloride) with a mixed salt that contains around 66% to 75% potassium chloride and the remainder being still sodium chloride (normal salt). Salts consisting of 100% potassium chloride tend to taste too bitter for most people.
You can use a lot of salt containing 66% potassium chloride and 34% sodium chloride given this way, you will always still consume around 3 times more potassium than sodium, which is a good ratio.
Thirdly, on top of replacing normal salt with potassium salt, one can also take extra potassium powder per day, as in the form of potassium chloride for example.
Keep in mind that potassium chloride consists of a potassium atom and a chloride atom. So 100 grams of potassium chloride contains 52 grams of potassium and 48 grams of chloride.
In other words, to get a specific amount of potassium, you need to take around double the amount of potassium chloride.
You can easily buy potassium chloride online or in many health stores.
When using 100% potassium chloride:
- After breakfast, add 2,000 mg (2 grams) of potassium chloride in one jar of water or another drink. This corresponds to around 1,000 mg (1 gram) of potassium.
- After dinner, add 2,000 mg (2 grams) of potassium chloride in one jar of water or another drink. This corresponds to around 1,000 mg (1 gram) of potassium.
When using a mixed salt consisting of 66% potassium chloride and 34% 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 grams of potassium. However, such a mixed salt would still contain 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 – which consists of about 40% sodium and 60% chloride).
As mentioned before, given by using such a mixed salt you always take about 3 times more potassium than sodium, your ratio of potassium-sodium is ok.
It’s important to always add these salt to a large amount of liquid given a too high concentration of potassium chloride or sodium chloride can damage the lining of the esophagus or stomach (they are salts after all).
10. Vitamin A
Vitamin A is also an often underestimated vitamin.
Vitamin A is needed for proper vision and epithelial health. Epithelial cells are cells that line many surfaces in and on 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 they leak from the gut through the epithelial cell lining in the bloodstream where they cause inflammation, among many other (bad) things.
Vitamin A also can help with dry or itchy eyes, which is caused by damage to the epithelial cells that line the outside of the eye (the cornea).
There exist two main kinds of vitamin A:
- Animal-derived vitamin A, called retinoids, and
- Plant-based vitamin A, called carotenoids.
For vitamin A to be active in our body, it needs to be converted in the animal-based retinoid form.
Vegetables 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. However, the body is quite bad at 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. Therefore, as a supplement, it’s preferable to take the animal-based, active form of vitamin A, namely the retinoid form, like retinyl-palmitate, instead of the carotenoid form.
As mentioned before, many people do not consume sufficient amounts of animal-based vitamin A, especially in recent times. This was different a while ago, when people still consumed lots of organ meat; including liver, which is very rich in vitamin A. Even my grandfather regularly ate liver, something that people currently hardly do anymore.
However, I prefer taking supplements of animal-based vitamin A instead of consuming an animal product like liver. Ideally, one takes around 2500 to maximum 5000 units of vitamin A per day.
One has to be careful with taking too much vitamin A. We see in studies that too much vitamin A, like 20,000 units or more per day, can lead to problems with bone formation for example. One reason for this is that vitamin A and vitamin D need to be in balance with each other; too much vitamin A and too little vitamin D can lead to bone problems. Therefore, I would keep the amount of vitamin A at the lower end.
11. Vitamin C
Vitamin C is often described as an antioxidant, but has many other, more important, effects in the body. For example, vitamin C improves the epigenome and mitochondrial functioning.
Especially vitamin C’s role in epigenetic health is interesting. Vitamin C works together with the anti-aging supplement alpha-ketoglutarate (AKG); both vitamin C and alpha-ketoglutarate are needed for TET enzymes to function properly, which are important enzymes involved in the maintenance of the epigenome.
As discussed earlier, a decline of the epigenome plays an important role in aging, it’s in fact one of the causes of aging.
I take vitamin C two times 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 can be iron deficient despite various iron deficiency biomarkers being normal (R).
However, iron can be a sword cutting at two sides: too little is not healthy and can significantly impair quality of life, but too much iron can also be unhealthy: it causes a lot of oxidative stress, and could increase the risk of diseases like Parkinson’s disease or Alzheimer’s (R,R) – albeit that too little iron could also increase the risk of Parkinson’s disease (R,R).
Therefore, I recommend supplementing with low levels of iron, like around 15 mg of iron per day. This is way lower than amounts that medical doctors sometimes give to treat iron deficiency, like 80 to 300 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 important mineral for health. It’s needed for proper immune system function, skin health and brain health, among many other things. Many proteins in our body need zinc to function properly, including proteins involved in DNA synthesis and protein production.
Typical signs of zinc deficiency are eczema-like lesions in the skin, hair loss, wounds that heal slowly, decreased sense of taste and smell, and diarrhea. Especially vegetarians are at high risk of not consuming too much zinc.
Zinc intake can reduce inflammation (R) and oxidative stress (R).
People with low levels of zinc have more risk of infections like pneumonia (R), and supplementing elderly people with zinc could improve immune function (R).
Zinc is also important for brain health. People with Alzheimer’s disease often have deficiencies in zinc (but also in many other substances), and supplying zinc could slow down the progression of Alzheimer’s (R).
However, as is the case for all other metals, one has to be careful not oversupplementing with zinc, which can be harmful. Do not take too much zinc (e.g. 40-50 mg per day), given too much zinc can cause too much oxidation, and hinder the absorption of other minerals like copper.
Therefore, one can take 15 mg per day of zinc, unless one’s multivitamin contains a dose of zinc similar to this.
14. A multivitamin
“Should I take a multivitamin?” is a question I have heard a gazillion times.
Doctors often have strong opinions about multivitamins: some of them find supplements completely useless (“they are only good for making expensive urine”), while others are big proponents of a daily multivitamin. As I will explain here, it’s a complex story.
First, let me start with the many shortcomings of multivitamins. Next, I’ll tell you why taking a multivitamin is still ok, on the condition that you incorporate it in the right way into your longevity routine.
Problems with most multivitamin supplements
Most multivitamin supplements are far from ideal. They have many shortcomings:
- Most multivitamins contain too low doses. For example, they contain too little potassium (e.g. 80 mg of potassium, while one needs to consume at least 4,700 mg of potassium per day), too little calcium (e.g. 50 mg of calcium, while one would need to consume 1,000 mg of calcium per day), too little magnesium (e.g. 70 mg of magnesium; ideally one consumes 350 to 450 of magnesium per day), too little vitamin D (most supplements contain maximum 400 units of vitamin D, instead of ideally 4,000 to 5,000 units per day), and so on.
- Most supplements contain the wrong forms of vitamins and minerals. For example, they contain (semi)synthetic vitamin E and not natural vitamin E. This (semi)synthetic vitamin E is in most cases “alpha-tocopherol acetate” or “alpha-tocopherol succinate”. Ironically, alpha-tocopherol succinate can actually be a pro-oxidant and have lysosomal toxicity (R,R). Most supplements contain folic acid instead of folate. Folate is the preferred form; it’s the natural form of vitamin B9/B11, and is better metabolized than folic acid (more specifically, ideally supplements contain methyltetrahydrofolate, and this as a glucosamine salt). Most supplements contain magnesium oxide, while magnesium malate or magnesium glycinate are preferred, as I explained earlier when talking about the best magnesium supplements. Many supplements also contain selenium methionine, while selenium yeast is better (given it contains different types of selenium; which brings us to the next point).
- Most supplements do not contain the different types of a micronutrient occuring in nature. For example, most supplements contain only one type of vitamin E (alpha-tocopherol) and not the 7 other types of vitamin E that also exist in nature, such as beta-tocopherol, gamma-tocopherol, alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, and so on. In fact, when a supplement contains lots of “vitamin E” of only one form (e.g. alpha-tocopherol), it can actually hinder the absorption of the other forms of vitamin E, which is not good. Something similar goes for omega-3 fatty acids: in nature, omega-3 acids can be found in phospholipid form, triglyceride form and lysophosphatidylcholine (LPC)-form. These forms have different effects in the body (for example, the LPC-based omega-3s can penetrate the brain-blood-barrier much better). Ideally, a supplement would contain all these different forms.
- Many supplements use wrong combinations, like combining micronutrients that inhibit each other’s absorption. For example, they contain calcium and iron, while calcium inhibits the absorption of iron. Or they contain zinc and copper, while zinc inhibits the absorption of copper. However, some multivitamins try to compensate for this by increasing doses. Also, despite they can inhibit each other’s absorption, a specific amount of these minerals is still taken up (but often less than the amount mentioned on the label).
- Some supplements contain too high doses of specific substances. For example, they contain too high doses of vitamin B6, which can cause nerve damage in the long term. In the US the tolerable upper intake level of vitamin B6 for adults is 100 mg, while in Europe it’s 25 mg (however, other B vitamins can be safely taken in very high doses). Other supplements contain too high doses of vitamin E, or too high doses of antioxidants which might impede the production of our own antioxidant enzymes, which could actually accelerate aging.
- Many supplements do not contain important micronutrients. For example, they only contain four types of B vitamins, while many other B vitamins exist.
- They use the wrong ratios of micronutrients (e.g. a too low dose of vitamin D and a too high dose of vitamin A).
- They use low quality micronutrients, like low-quality glucosamine or too oxidized vitamin E or too oxidized omega-3 fatty acids.
These important, very common problems with multivitamins also help to explain why most multivitamin studies actually don’t show any benefits.
It’s then not that surprising that many medical doctors are weary of supplements, given many supplement studies indeed do not show effects.
But this doesn’t mean that vitamin and mineral supplements are worthless or ineffective. In the first place this means that many supplement studies have big shortcomings and design problems. In many supplement studies, the wrong forms, combinations, ratios, and low-quality supplements are used. So it’s not surprising that many vitamins and minerals do not seem to have an effect.
Besides these problems, there are other important shortcomings with supplement studies, explaining why supplement and multivitamin studies fail.
Problems with supplement studies
Some other important reasons why supplement studies do not show positive effects on health or longevity can be the following:
- Many supplement studies do not last long enough, e.g. they last a few months or years, not decades. But it takes decades for heart disease, Alzheimer’s, and other diseases to arise; so giving someone B vitamins for 6 months is likely not going to make a big impact on a disease that took decades to form.
- Too late. Many studies start when the disease has already progressed too far. For example, scientists give a supplement to see if they can impact Alzheimer’s disease. But giving micronutrients is in many cases too late. When people have the symptoms of Alzheimer’s disease (like forgetfulness, confusion, etc), dozens of brain cells have already died off, and a lot of other damage in the brain has happened. Supplements are not going to conjure back those dead brain cells. Ideally, one would give these micronutrients 15 years before Alzheimer’s originates; but such a study would be prohibitively long and expensive to run.
- Many studies use only one or a few micronutrients, while many micronutrients work together synergistically. For example, to test if B vitamins can slow down brain atrophy, some clinical trials used only two B vitamins instead of using more B vitamins (given many B vitamins work synergistically – and B vitamins on their turn work synergistically with omega-3 fatty acids for example (R,R)). For a study examining the effects of vitamin A, often only vitamin A is given, while vitamin A works together with vitamin D to perform various important functions. It’s like trying to see if wheels are useful for cars. If you only use one wheel on a car, you will conclude that wheels are not useful for cars because the car of course cannot drive properly with one wheel. It’s only when you use four wheels that the car drives very well, and that wheels are indeed very important for cars to function properly.
- Patients are often already treated with lots of medication, reducing the potential effect a supplement may have. For example, some trials do not show beneficial effects of omega-3 fatty acids on heart disease (I will not go deeper into this highlighting that lots of these trials use a too low dose, too oxidized omega-3s, not the ideal forms, etc). However, the patients in lots of these trials already take high amounts of medication which can already significantly reduce their risk of a heart attack, such as blood-pressure drugs, cholesterol-lowering drugs, aspirin, ACE-inhibitors, anti-inflammatories, etc. So adding omega-3 fatty acids to this mountain of medication that already significantly reduces the risk of a heart attack can make that an additional positive effect of omega-3s is too small to be noticed.
- The use of crude biomarkers of disease and health. Medicine is still in its infancy, meaning we cannot yet treat most diseases properly, and that it’s difficult to just even “diagnose” or “measure” diseases. For example, it’s very difficult to accurately measure the severity of Alzheimer’s disease. There exist all kinds of Alzheimer’s ratings scales, which ask patients questions like which day we are, or ask them to draw a clock with a specific time on it, and so on. But as you might have guessed, this is not very accurate. If people had a bad night of sleep, or just returned from a sugar-rich food-coma inducing meal, or just had a cup of coffee, this can impact these test results significantly. Even looking at clinical endpoints, such as heart attacks or hospitalisations is not that accurate given not all of them are reported, or they are wrongly reported, and so on.
- Medicine is messy. Many confounding factors exist that increase or decrease the risk of a specific disease. Many supplements (and drugs) fail, not necessarily because they are not effective, but because there are so many confounding factors that can skew the data. For example, in one study, a drug doesn’t work. But when the same drug is tested in another country, it does work. The reason is that in the other country there is more sunlight, so higher vitamin D levels, which impact how the drug works in the body. In other cases, an artificial sweetener does not impact blood sugar levels. However, if you further analyze the study, you find that in 20% of people the artificial sweetener does cause significant dysregulation of their blood sugar levels; depending on the kind of gut microbiome participants have.
As you can see, it’s very difficult to conduct a proper clinical trial. Therefore, if a study doesn’t show an effect of a supplement (or drug), that doesn’t necessarily mean that the supplement (or drug) doesn’t work. So many other factors can have contributed to this “failure”. However, if a supplement does show an effect (e.g. supplement x reducing risk of heart disease), this is more likely a significant effect, given despite all the confounding factors which can mess up the result, there is still this result bubbling up surrounded by an turbulent ocean of data.
An extra compounding factor is that many studies are sponsored by companies. Scientific studies have shown that when a study is sponsored by a company, there is many times more likelihood the study is in favor of the result the company wants to see.
To make a long story short, multivitamins and supplements have lots of shortcomings, and so do the clinical trials conducted with these supplements.
Best way to take a multivitamin
I have been bashing multivitamins a lot. This doesn’t mean that multivitamins are useless.
One can still take a multivitamin. It’s a way to make sure you take in sufficient amounts of micronutrients which can be found in the right dose and form in most multivitamins, such as manganese, molybdenum, copper, zinc, iron, and so on.
However, given most multivitamins contain too low doses of many other minerals, vitamins and micronutrients, one needs to take these on top of your multivitamin. This means taking:
- Extra vitamin D (around 4,000 to 5,000 units per day – most multivitamins only contain 400 units)
- Extra magnesium (350 to 450 mg of magnesium – most multivitamins contain too little magnesium)
- Around 800 to 1000 mg of calcium per day (most multivitamins contain only 50 to 100 mg)
- A B vitamin complex (which contains several times the daily recommended amount of B vitamins)
- Extra iodine (most supplements only contain 75 or 150 ug of iodine – ideally one takes at least around 300 to 450 ug of iodine per day)
- Potassium at least 2000 mg extra per day (most multivitamins only contain 50 to 100 mg).
However, even taking these extra amounts of specific vitamins and minerals still won’t cut it for some substances.
These are substances that almost no supplement provides in the right form and dose. This is the case for vitamin E. It’s advised to take vitamin E not via supplements but via food given that almost all supplements do not contain the right form and doses of vitamin E (as I explain later in the part about vitamin E).
About 90 percent of people do not reach their daily required intakes of vitamin E.
Interestingly, if you measure vitamin E levels of people in their blood, most people have “normal” vitamin E levels.
This should not be surprising though, given blood tests are not good in tracking vitamin and mineral deficiencies, as I explained in another chapter.
What also should not be surprising is that so many people are deficient in vitamin E. Not a lot of foods contain vitamin E. And even the foods with the most vitamin E still do not contain that much vitamin E. So it’s very difficult to get enough vitamin E on a daily basis.
Therefore, some people resort to vitamin E supplements. However, this is also not ideal.
The problem with vitamin E supplements
Most vitamin E supplements do not contain natural vitamin E, but synthetic or semi-synthetic forms of vitamin E.
This “vitamin E” is artificial “alpha-tocopherol acetate” or “alpha-tocopherol succinate”.
This is not ideal. In fact, alpha-tocopherol succinate is even a pro-oxidative substance instead of an antioxidant (R). It can also cause lysosomal and mitochondrial destabilization (R).
Because of its toxicity, some scientists even proposed to use alpha-tocopherol succinate to treat cancer given cancer cells are especially vulnerable to this kind of toxicity.
Anyhow, it’s clear that these synthetic variants of vitamin E have very different effects than the natural vitamin E.
Furthermore, in nature various different forms of vitamin E exist, while most vitamin E supplements contain only one form of vitamin E, namely alpha-tocopherol.
However, in nature there exist 8 forms of vitamin E, like alpha-tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, alpha-trienol, beta-trienol, gamma-trienol, and delta-trienol.
So if you take a vitamin E supplement, you in most cases only take one form of vitamin E (alpha-tocopherol), and then even very likely the artificial form.
Even worse, if you only take one form of vitamin E, especially in high doses, this form can inhibit the absorption of the other forms of vitamin E you get via food, further increasing deficiencies of these natural forms of vitamin E.
There are some supplements that offer multiple different forms of natural vitamin E (supplements containing mixtures of different tocopherols and tocotrienols), but these still often do not contain all 8 forms of vitamin E found in nature.
Another problem is that these supplements often contain way too high doses of vitamin E, like 300 to 400 mg of vitamin E while the recommended daily amount of vitamin E is around 15 mg.
These problems with vitamin E could also help to explain why vitamin E supplementation, especially in high doses, can increase mortality (R).
Given it’s so difficult to take the proper, natural forms of vitamin E via supplements, it’s best to take vitamin E via food. However, this is easier said than done.
The best way to take vitamin E
The best way to get vitamin E is by consuming vitamin E-rich foods on a daily basis.
Foods rich in vitamin E are almonds, hazelnuts and sunflower seeds.
However, even these “vitamin E-rich” foods do not contain that much vitamin E, so you need to eat a lot of them. Therefore, I would recommend eating two or three handfuls of almonds, hazelnuts and/or sunflower seeds per day.
On top of these, you can add other “vitamin E-rich foods” like avocado or green leafy vegetables, but these already contain much less vitamin E compared to the nuts and seeds I just mentioned.
That’s why almost after every meal I eat almonds or sunflower seeds (they are good in reducing any remaining appetite you still hadd).
And almost every morning I eat avocado (snippets), for example together with blueberries, quinoa flakes, walnuts, mixed with vegetable yogurt (e.g. almond yogurt or soy yogurt) or vegetable milk (e.g. cashew milk, almond milk, soy milk, etc). This is an easo-to-prepare and very healthy breakfast, with extra vitamin E from the avocado.