We are often asked why we didn’t include specific “anti-aging” ingredients in NOVOS’ longevity formulations.
For example, why didn’t we include quercetin, nicotinamide riboside (NR), astragalus, or EGCG in NOVOS Core or Boost?
There are various reasons why we don’t include certain ingredients in our formulations.
First, there are stringent requirements that must be met for an ingredient to be adequate for consideration in a NOVOS product, which you can learn more about here.
There are also additional reasons why we may decide against specific ingredients. Here are some of the more common reasons why some popular ingredients were not included:
- There are not enough studies demonstrating that the ingredient can extend lifespan, ideally in multiple species (e.g., EGCG or curcumin)
- The studies demonstrating lifespan extension are not done in normal healthy organisms, but in animals with specific mutations that are not representative of normal aging (e.g., coenzyme Q10)
- There are not sufficient studies demonstrating that the substance acts on one or multiple hallmarks (mechanisms) of aging
- Contradictory studies (e.g., acetyl-cysteine)
- Better alternatives are available (e.g., fisetin vs. quercetin)
- Inadequate safety data or data that indicates the possibility of damage caused by the substance (e.g., quercetin).
Below you will find a list of ingredients we have studied and purposely not used in our NOVOS Core and NOVOS Boost formulations, and our reasons why.
It’s crucial to note that science — the acquisition of knowledge through experimentation — is a continually evolving field. As a company, NOVOS and its scientific team of researchers and formulators are open-minded to changing positions on ingredients as new scientific evidence becomes available and exceeds our high standards of scientific scrutiny.
The analysis presented below is based on the current best available evidence.
New scientific findings that may further solidify our position or lead to an altered consideration will be continuously posted on this page.
Table of Contents
- Quercetin (vs. fisetin)
- EGCG and green tea extract (vs. theanine)
- Curcumin (turmeric)
- Resveratrol (vs. pterostilbene)
- Astragalus and telomerase activators like TA-65
- Co-enzyme Q10 (coQ10)
- Nicotinamide riboside (NR) (vs. NMN)
- MCT (medium chain triglycerides)
- Antioxidants
- Beta carotene and carotenoids (including crocin)
- Apigenin
- Blueberry extracts and procyanidins
- Vitamin A, vitamin E, and other vitamins and minerals
- Alpha-lipoic acid (ALA) and R-lipoic acid
- Berberine
- NAC (N-acetyl-cysteine or N-acetyl-L-cysteine)
- Trimethylglycine (TMG or betaine)
- Glutathione
- Pyrroloquinoline quinone (PQQ)
- Acetyl-L-carnitine (ALCAR)
- Whey protein
- D-ribose
- Ergothioneine
- Astaxanthin
“Anti-aging” Supplements Less-Than-Ideal or Counterproductive For Human Anti-Aging/Longevity
1. Quercetin (vs. Fisetin)
Quercetin is often touted as an anti-aging substance, given it can clear senescent cells.
However, after careful analysis, we prefer fisetin over quercetin.
Fisetin looks very similar to quercetin, but contrary to quercetin, fisetin has more convincing studies showing it can extend lifespan and mitigate aging (R,R,R,R,R).
After consulting with our Scientific Advisory Board, which contains subject matter experts on both quercetin and fisetin, we determined it would be best to use a continuous, relatively low dose of fisetin, rather than a very high “pulsed” senolytic dose of quercetin every few weeks to “clear” senescent cells. High doses of quercetin could damage healthy cells (not only senescent cells), especially stem cells.
The lifespan studies with fisetin used a continuous lower dose of fisetin (R). At lower concentrations, fisetin has potent anti-inflammatory effects and has epigenetic, mTOR-inhibiting, and other anti-aging benefits (R,R,R).
Learn more about the anti-aging benefits of fisetin here.
2. EGCG and Green Tea Extract (vs. Theanine)
Epigallocatechingallate (EGCG) is a substance found in green tea. EGCG can, in some studies, extend lifespan, especially in more simple organisms like C elegans (R). Unfortunately, in more rigorous mice studies, EGCG and green tea extract didn’t extend lifespan (R).
Although EGCG may have other uses, for the sake of human longevity, we prefer theanine.
Theanine is also a substance found in green tea and has demonstrated various interesting effects on aging and protecting cells against damage, such as reducing Advanced Glycation End products (AGEs) (R,R) and cellular stress (R,R,R,R). Theanine has been shown to extend lifespan (R,R,R).
Theanine also has the added benefits of improved cognition and reducing stress (R,R).
Learn more about the anti-aging benefits of theanine here.
3. Curcumin (Turmeric)
Curcumin is a substance found in turmeric. In some studies, it can extend lifespan, but in more rigorously conducted experiments in mice, it unfortunately didn’t extend lifespan (R). In other words, the jury is still out there.
Curcumin may offer various health benefits, however. For example, it can reduce inflammation (“inflammaging“) and also help to reduce protein clumping, an important aging process.
It’s also worth noting that many supplements boast of extremely high levels of bioavailability for their curcumin, some touting levels approximately 2,400% higher than natural absorption. However, more is not necessarily better; we all know the age-old Paracelsus-derived adage, “The dose makes the poison.” To our knowledge, there is currently inadequate research to demonstrate that such high levels of curcumin absorption would in fact be beneficial in the long term.
4. Resveratrol (vs. Pterostilbene)
Resveratrol is not short of controversy and has certainly not lived up to longevity expectations, especially in humans. Early studies showed that resveratrol (made famous by researchers like Dr. David Sinclair for its presence in grape skin and red wine) can extend lifespan in various animals (R,R,R,R). However, recent or better-conducted studies have shown that resveratrol doesn’t extend lifespan (R,R), nor does it have favorable effects in humans.
One reason for this could be that resveratrol is broken down very quickly in the body. Resveratrol’s half-life is only 14 minutes, meaning that after 14 minutes, already half of the resveratrol is eliminated by the body; at an hour, more than 90% of resveratrol has been broken down.
On the other hand, a similar molecule to resveratrol, also in the stilbene family of natural compounds is pterostilbene (highly present in blueberries), which can circulate in the body for much longer – as long as 105 minutes (versus 14 minutes for resveratrol), according to experiments in multiple animal species. This is because pterostilbene contains only one hydroxyl group, compared to the three hydroxyl groups of resveratrol. Hydroxyl groups make it much easier for the body to get rid of a molecule.
Pterostilbene is considerably better absorbed by the gut compared to resveratrol. Pterostilbene has a bioavailability of about 80 percent, compared to 20 percent for resveratrol. This means that pterostilbene is about four times better absorbed compared to resveratrol.
Pterostilbene is also more lipophilic, which enables it to more readily pass through cellular membranes and into the target cells than resveratrol.
As if that wasn’t adequate reason to choose pterostilbene over resveratrol, pterostilbene also contains three methyl groups, which can assist the epigenome with methylation, and with the production of an endogenous longevity molecule, NAD+.
In our assessment, and that of many scientific labs, pterostilbene is the superior molecule.
Learn more about pterostilbene here.
5. Astragalus And Telomerase Activators Like TA-65
Astragalus is a small plant that contains substances that could lengthen telomeres.
Shortening of telomeres contributes to aging, especially in fast-dividing cells and in stem cells (learn more here about some common misconceptions about telomeres and aging).
However, despite some studies showing lifespan effects of Astragalus in simple organisms like silkworms (R), at this stage, there is not yet sufficient scientific evidence to incorporate it in NOVOS’ formulations.
Other studies found no effect of Astragalus on lifespan, or found that a high dose of Astragalus can actually reduce lifespan in some organisms (R).
TA-65 is an “anti-aging” supplement made from extracts of the Astragalus membranous plant. The company that sells TA-65, T.A. Sciences, claims it can lengthen telomeres.
However, studies in mice show that TA-65 did not extend lifespan. According to the authors, “TA-65 administration for 4 months did not change statistically the mean or maximal lifespan of female mice under our experimental conditions.” (R)
While this study found that TA-65 lengthened telomeres in mice (despite not extending their lifespan), another study found that TA-64 did not extend telomeres in chickens (R).
That is why we opted for other, more interesting substances that can also lengthen telomeres, like lithium (R,R,R,R) and magnesium (R).
These substances have much more studies supporting life-extending effects and can slow down aging in various ways (not only by extending telomeres).
6. Co-enzyme Q10 (coQ10)
Many companies sell co-enzyme Q10 (coQ10) as an anti-aging supplement. However, co-enzyme Q10 is likely not a proper anti-aging substance.
Yes, there are studies that show very high doses of coQ10 doses could perhaps somewhat reduce the progression of Parkinson’s disease or heart failure (R,R) — or not (R).
However, given co-enzyme Q10 is an antioxidant, it could actually reduce lifespan (learn more how antioxidants can accelerate aging here).
Various studies in animals show that co-enzyme Q10 does not extend lifespan and can actually shorten lifespan (R,R).
Other studies demonstrate that mice or other organisms that have less or dysfunctional co-enzyme Q10 actually live longer instead of having shorter lifespans (R,R,R).
There are also studies showing that co-enzyme Q10 can extend lifespan, but often these studies have not been well conducted, or they use organisms that are not an ideal representation of normal aging.
For example, they use mice with rare mutations, making them deficient in co-enzyme Q10; giving co-enzyme Q10 in this “artificial” context will of course help.
Lastly, the interventions testing program (ITP) tested a similar compound, MitoQ (a better-absorbed nutrient that is based on coQ10), and didn’t find a life extension effect (R).
With that said, there are many doctors who prescribe coQ10 to their patients. It is important to always work with your doctor.
7. Nicotinamide Riboside (NR) (vs. NMN)
Nicotinamide riboside (NR) is often promoted as an “anti-aging supplement.” It is pushed a lot by companies because its production process is patented (contrary to many other supplements, like NMN).
Many companies claim NR can slow down aging and extend lifespan. However, studies show that in normal healthy animals (so not animals with a strange mutation that accelerates aging), nicotinamide riboside (NR) does not extend lifespan (R).
Therefore, we prefer NMN instead of NR, for reasons we explain in detail here.
8. Medium Chain Triglycerides (MCT)
MCTs are saturated fatty acids of medium length. They can be found, for example, in coconut oil.
Medium chain triglycerides can serve as an alternative source of energy, for example during fasting or for brain cells. These fatty acids have a propensity for being converted into ketones by the liver.
Despite the excitement surrounding ketones, giving mice MCTs didn’t extend lifespan (R).
Further, ketones on their own have not been found to extend lifespan. Rather, processes, like fasting or reduction of mTOR activation and insulin secretion via low protein and carb intake, are likely to be the factors influencing longevity.
9. Most Antioxidants
First, it’s important to distinguish between different types of antioxidants. In the purest sense, an antioxidant is counteracting an oxidant, which can cause damage via oxidation. If excess oxidation accumulates, inflammation can occur.
However, there are many substances characterized as antioxidants that are not actually such in the pure sense of the word. Instead, these “antioxidant” molecules cause small amounts of damage, or oxidation, which then stimulates the body to upregulate its own antioxidant defenses (e.g., glutathione, superoxide dismutase, etc.). This process is known as hormesis, so these “antioxidants” are hormetic antioxidants. Examples include EGCG, curcumin, berberine, etc.
Let’s start with the “pure” form of antioxidants, like vitamin E, exogenous glutathione, coQ10, etc.
Despite many people believing that antioxidants can slow down aging and extend lifespan, unfortunately, most antioxidants do not slow down aging, nor extend lifespan.
Many large studies have shown that people who take antioxidants do not live longer. In some cases their lifespan can be shortened or there is increased mortality (R,R,R).
This can be explained in various ways. When cells are exposed to antioxidants, they don’t make their own antioxidant enzymes, which are much more powerful than the antioxidant effects of antioxidant supplements. Also, orally administered antioxidants cannot reach ideal concentrations in specific compartments in our cells (like in the mitochondria).
Other studies demonstrate that taking antioxidants after exercise blunts the health effects of exercise (R). This is because exercise produces a healthy amount of acute cellular stress via free radicals. These free radicals serve as signaling molecules — information — that the body uses to come back better and stronger. If an antioxidant intercepts these free radicals, the body does not receive this crucial information that is needed to deliver adequate repair in the form of muscle growth or improved fitness.
In some cases, antioxidants can increase the risk of cancer and help cancer cells to spread around the body (to metastasize faster) (R,R,R,R,R).
This makes sense: cancer cells divide and multiply a lot and spend less energy on proper antioxidant defenses. Taking extra antioxidants can actually help cancer cells to survive and multiply faster by protecting them against free radical damage.
We wrote more about antioxidants and aging here.
10. Beta Carotene And Other Carotenoid Supplements (Including Crocin)
Beta carotene is a carotenoid and a precursor to vitamin A. Carotenoids give carrots, pumpkins, and other fruits and vegetables their typical orange color.
Carotenoids have been associated with various health benefits. But can carotenoid supplements increase lifespan?
Likely not. Taking beta carotene supplements has been associated with reduced lifespan, increased mortality, and a greater risk of getting cancer and dying of cancer (R,R,R).
One explanation could be that taking large doses of beta carotene hinders the absorption of other carotenoids. The transport proteins in the gut that take up carotenoids get oversaturated with only beta carotene, so they cannot take up other carotenoids.
Corcin is also a carotenoid and an antioxidant. As mentioned before, many antioxidants do not extend lifespan or can even shorten lifespan.
Also, to our knowledge, there are no convincing in-vivo studies demonstrating that corcin can extend lifespan.
11. Apigenin
Apigenin is a flavonoid found in parsley, celery, and chamomile.
Flavonoids can have various beneficial effects on health and aging. Apigenin is an interesting and promising molecule for health and longevity (R,R).
However, we prefer fisetin to apigenin. Fisetin is related to apigenin (they are both flavonoids). But there is more research demonstrating that fisetin extends lifespan and acts on aging mechanisms compared to apigenin (learn more here).
You can also just drink chamomile tea, which contains apigenin (and many other healthy substances) and has been shown to be associated with longer lifespans (R).
12. Blueberry Extracts And Procyanidins
Blueberry extracts contain various healthy substances, such as proanthocyanidins, cyanidins, and pterostilbene.
Blueberry extracts could lengthen lifespan, according to some studies (R,R).
Specific substances found in blueberries, like pterostilbene, can have various beneficial effects on health and longevity, but only in doses much higher than found in blueberry extracts (R,R,R,R,R).
Therefore, we recommend eating blueberries on a daily basis and taking specific longevity substances like pterostilbene in supplement form.
13. Vitamin A, Vitamin E, And Other Vitamins And Minerals
Most vitamins and minerals unfortunately do not extend lifespan (R,R,R).
However, vitamins, minerals, and other micronutrients are still important for optimal health.
A deficiency in specific vitamins and minerals can shorten lifespan. But taking extra vitamins and minerals while not being deficient does not extend lifespan.
We explain more about the role of vitamins and minerals in health and longevity here.
14. Alpha-lipoic Acid (ALA) And R-lipoic Acid
Alpha lipoic acid is often promoted as an anti-aging substance.
There are studies demonstrating the beneficial effects of alpha-lipoic acid (ALA), mainly in rodents but also in humans. For example, ALA could perhaps reduce the progression of Alzheimer’s disease (R) and improve metabolic diseases like diabetes (R).
But what about lifespan?
Studies show that alpha-lipoic acid can actually reduce lifespan (R).
This makes sense. Alpha-lipoic acid is a strong antioxidant. ALA can perhaps reduce some damage that is happening during, for example, Alzheimer’s disease (like oxidative stress), but as an antioxidant, it lowers the cell’s own antioxidant defense mechanisms, which might actually speed up the aging process.
15. Berberine
Berberine is often touted as a supplement that can improve insulin resistance. Berberine can also activate AMPK, an important metabolic regulating protein associated with improved insulin sensitivity for example. However, berberine is an alkaloid, which often are quite toxic compounds.
In our opinion, there are not enough studies showing that long-term berberine intake is safe, or even better, that berberine can extend lifespan in multiple different organisms.
We wrote more about berberine versus metformin here.
16. NAC (N-acetyl-cysteine or N-acetyl-L-cysteine)
N-acetyl cysteine (NAC) is a strong antioxidant. Many studies show that antioxidants do not extend lifespan and can even accelerate aging, as we explain here.
This can help to explain the contradictory studies with NAC. Some studies show that acetyl-cysteine extends lifespan, mostly in simple organisms (R,R,R), but also in mice — however, in mice, the results are open to interpretation (R).
However, other studies show that NAC can actually shorten lifespan (R).
There are also studies demonstrating that N-acetylcysteine increases the spread (metastasis) of cancer (R,R).
This could make sense: cancer cells are fast-dividing cells that don’t regulate their metabolism well, so they produce lots of free radicals. Antioxidants like NAC mop up these oxidants, something which can be very helpful for free-radical-ridden cancer cells.
So to err on the side of caution, we currently do not advise taking N-acetyl-cysteine.
17. Trimethylglycine (TMG or Betaine)
Trimethylglycine (TMG), also called betaine, is a substance that is sometimes recommended for health or longevity purposes, mainly to improve methylation (which is the process of adding small molecules called methyl groups to the DNA to regulate gene expression).
TMG was one of the many substances we looked into when formulating our foundational anti-aging product NOVOS Core.
However, we refrained from adding trimethylglycine to our formulation for several reasons. For example, in some patients, TMG can cause side effects, especially in the long term, such as disturbed sleep or gastro-intestinal issues.
Also, in the context of methylation (which is very important), TMG is a more downstream molecule in methylation pathways. We therefore recommend taking more upstream methylators, like choline and/or phosphatidylcholine (that way, the body can choose itself how much methylation donors it wants to create), and a B vitamin complex.
We explain more about choline and phosphatidylcholine on this page (see section 9 about choline).
We added glycine not specifically as a methyl donor but because of other reasons, for example glycine can help to protect the epigenome, especially in mitochondria, and has anti-inflammatory and various positive metabolic effects and extends lifespan in different species. We wrote more about glycine and longevity here.
Also, there are not sufficient well-conducted studies demonstrating that trimethylglycine extends lifespan in normal, healthy organisms.
Proper maintenance of the epigenome, however, is very important for longevity.
That is why NOVOS Core contains alpha-ketoglutarate, vitamin C (AKG and vitamin C work together synergistically, they are both substrates for TET enzymes for example), glycine, microdosed lithium, etc. This is also why NOVOS Boost contains NMN.
These are all molecules shown to help to maintain and protect the epigenome.
18. Glutathione
Glutathione is an antioxidant. It’s a tripeptide, meaning it’s composed of three amino acids (glycine, cysteine, and glutamate). Glutathione occurs naturally in the body and helps cells to protect themselves against free radicals. Quenching free radicals is what antioxidants do.
However, many studies have shown that most antioxidants don’t really work to extend lifespan.
Some antioxidants can even shorten lifespan, while other studies show that often reviled free radicals (the “deleterious” molecules that antioxidants neutralize) can actually extend lifespan, or confer health benefits (R,R,R,R) — in the right doses.
We explain more about the disappointing effects of antioxidants here. We also have a list of antioxidants you should not take for anti-aging.
Another issue with glutathione is that it cannot be absorbed by the gut in one piece. When taken orally, our digestive system cuts the glutathione up into its individual amino acids (this also happens with liposomal forms of glutathione).
Some scientists speculate that the digestion of glutathione is not necessarily a bad thing, given this way you provide the building blocks (amino acids) to create glutathione in your own cells.
While there are some studies showing that glutathione can improve lifespan, often these studies are not very high-quality. More recent studies show that substances like glutathione and even their precursors, like cysteine, can shorten lifespan (R).
All in all, lifespan studies with glutathione and many other antioxidants have been disappointing.
Regarding glutathione specifically, we believe the data is not yet clear enough to conclude whether or not it is beneficial for longevity purposes.
19. Pyrroloquinoline Quinone (PQQ)
PQQ is a strong antioxidant. As we explained earlier, most antioxidants do not extend lifespan, and some can even increase mortality (at least according to well-conducted studies).
There are some small studies that show that PQQ can extend lifespan in C elegans, but so have coenzyme Q10 and many other antioxidants that have later been shown to not extend lifespan in larger, better-conducted experiments (R,R). Other studies show that when coenzyme Q10 is downregulated, organisms actually live longer (R,R,R).
However, PQQ could also exert other effects in cells besides being an antioxidant. We currently believe there is not enough evidence that PQQ can extend lifespan.
20. Acetyl-L-carnitine (ALCAR)
This molecule can be found in our cells, including the mitochondria.
Studies show that acetyl-L-carnitine (ALCAR) can improve some health aspects, like muscle performance, metabolism, energy levels, nerve damage (neuropathy) and perhaps slowing down the early stages of Alzheimer’s disease.
Regarding lifespan extension, there is less scientific evidence. There are other supplements that have better science behind them demonstrating they can slow down aging, as we explain here.
21. Whey Protein
Whey protein is a milk-derived, animal-based protein.
One main finding in biogerontology (the science that studies aging) is that too much animal protein accelerates aging (R,R,R,R,R,R,R,R,R,R,R,R,R,R). We explain more here.
Despite this, many people still advise high animal protein diets. Of course, if you follow a high-protein diet (which also mainly involves cutting back on carbs), you will feel better in the short term and lose weight, too.
This might be good for you in the short term if you’re very overweight and have cardiovascular or metabolic risks. But in the long term, too much animal protein accelerates aging. Therefore, we don’t recommend whey protein for anti-aging purposes.
22. D-ribose
D-ribose is a sugar-like molecule.
There is not a lot of convincing science or well-conducted studies showing that ribose can extend lifespan.
Some studies seem to suggest that ribose can increase energy levels and muscle performance.
23. Ergothioneine
Ergothioneine is an amino acid found in mushrooms. It’s often touted as a strong antioxidant, but this has been mainly observed in vitro (in a lab dish), not in vivo (in organisms).
In vivo, ergothioneine’s antioxidant activities are less pronounced. In vivo, ergothioneine likely does not act as a primary antioxidant but functions more as a secondary antioxidant that kicks into action when primary antioxidants are depleted or when primary antioxidant mechanisms are overwhelmed.
However, ergothioneine likely has many other beneficial effects besides being an antioxidant. For example, ergothioneine could impact fatty acid oxidation or impact tyrosine metabolism.
Various studies show protective effects of ergothioneine in organisms (R,R,R). However, the most interesting studies are ones that can demonstrate lifespan extension; ideally not only median lifespan extension but also maximum lifespan extension.
Currently, very few lifespan studies have been conducted with ergothioneine. One study showed that ergothioneine can extend lifespan in fruit flies (Drosophila melanogaster) (R). However, the study also found that at higher concentrations (10 mM) ergothioneine could shorten lifespan somewhat.
We have not included ergothioneine into our supplements because we would like to see additional lifespan studies, ideally not only done in fruit flies, but also in other simple organisms (like C elegans or yeast) and in more complex organisms like mice.
Ergothioneine has the potential to be an interesting longevity substance. However, given it’s an antioxidant and given that most antioxidants do not extend lifespan and can even shorten lifespan, we would like to see more studies before we would recommend it for longevity purposes.
If you want to naturally increase your uptake of ergothioneine, you can consume more mushrooms, especially porcini mushrooms and oyster mushrooms, which are very high in ergothioneine. Mushrooms in general contain many other substances that are healthy (like spermidine), and we do know that consuming more mushrooms contributes to increased health and longevity.
24. Astaxanthin
Astaxanthin is a promising substance that demonstrates various potential health benefits. It is often touted as a strong antioxidant, but astaxanthin could also mediate its health effects on aging via other, likely more relevant mechanisms, such as increasing autophagy (R), activating pro-longevity genes like FOXO3 (R), and improving mitochondrial function (R).
However, in the end, the most important thing we want to know is whether astaxanthin can also extend (healthy) lifespan. Currently, not a lot of studies have been done demonstrating that astaxanthin extends lifespan.
Some studies done in simple organisms like C elegans (R,R,R) show extension of lifespan, but ideally, we want to see more lifespan studies in additional organisms. Various substances have been shown to extend lifespan in simple organisms, especially antioxidants, but when tested in more complex organisms like mice (ideally, normal ones, not those with intentional genetic defects), we don’t find any lifespan extension effects.
Also, astaxanthin is a carotenoid. Some studies found that administering extra carotenoids like beta carotene shortens lifespan and can increase the risk of cancer and metastasis (R,R,R), despite that beta carotene also extends lifespan in C elegans.
We hold NOVOS formulations to the highest standards of safety and efficacy. Although astaxanthin is promising, it has not yet reached the threshold for inclusion in a NOVOS formulation. For now, until further studies clearly demonstrate more favorable and conclusive lifespan effects, astaxanthin will remain on the sidelines.
So what are some great anti-aging ingredients?
We listed them here.
