SIRT1 activation: When can I best take resveratrol, pterostilbene, curcumin and quercetin for optimal effect?

sirt1 golf meepakken

Key takeaways:

✓ Preferably consumed in the morning, or evening, but not during the day.

✓ Consume with water, with a small meal (breakfast).

✓ Want to increase SIRT1 whilst fasting? Consume with an oil such as MCT C8, which has no negative impact on your period of fasting.

✓ Not immediately before, or until 8 hours after intensive strength training (An article on this topic will follow).

Read more about the mechanism behind resveratrol here.

Find the best, evidence-based formulas to activate SIRT1 here.

Why is the moment of consumption of SIRT1 activators important?

There is no unequivocal conclusion in scientific research regarding the best time when one should take resveratrol for optimal results. The factor time of consumption is hardly included in the studies that have been done so far. Furthermore, in studies, participants are often given resveratrol or a related compound like pterostilbeen twice a day or even more frequently. As a result, you can’t say anything about differences in effect when ingested in the evening or morning.

The counterpart of SIRT1, mTOR, is suppressed by calorie restriction, meaning either: eating below caloric maintenance level, or through periods of fasting. Resveratrol has the potential to suppress mTOR, either by activation of AMPK or SIRT1 (2). mTOR is a protein that plays a role in protein synthesis and cell growth. To create a good balance between cell growth and cell protection, it is useful to stimulate both mechanisms at certain times. Uninterrupted cell growth is unfavorable, because cancer cells are then given free rein in their development.

It is therefore useful to activate SIRT1 and thus regularly suppress the mTOR mechanism, to alternate cell growth with cell protection. This effect has been frequently demonstrated in scientific research. For example, resveratrol as a SIRT1 activator is known to reduce the growth of leukaemic t-cells (3). However, too much SIRT1 activation might not be in your best interest. The accompanying autophagy is great, to a certain extent. One can go pretty long without eating, but if someone is lean and malnourished, it might be useful to stimulate cell growth rather than cell preservation. This will help hormonal balances or excessive weight loss.

Finding perfect balance between mTOR and SIRT1

At Elixir Life, we are in favour of a lifestyle that alternates activation of SIRT1 and mTOR in order to reap the benefits of both mechanisms. SIRT1 and mTOR can be seen as the yin and yang of cell growth and cell protection.

In case of illness, it may be useful to focus on SIRT1 activation, rather than to continuously stimulate mTOR. mTOR is stimulated by insulin, which means that eating generally stimulates mTOR, while SIRT1 is stimulated by calorie restriction. Because both mTOR and SIRT1 initiate useful bodily functions, we want to healthy people help finding the right balance between activation of SIRT1 and mTOR. This can be achieved by alternating periods of time during the day (or week, if you prefer), where both processes are optimally exploited. This gives the body the opportunity to recover and grow after intensive strength training, but also gives the body the chance to clean up unwanted cells and make healthy cells more resistant to stress.

yin yang balans sirt1 mtor
With our products we try to balance gene expression by activating SIRT1

Because resveratrol, pterostilbene, quercetin and curcumin initiate certain bodily functions, it may be useful to take products that stimulate this process at times when these functions would normally take place in the body. You don’t take sleeping pills after waking up and you don’t drink coffee before going to bed. People generally benefit more from taking supplements or stimulants to support bodily functions as they would naturally occur. Try not to fight the waves.

Natural activation of SIRT1

To determine the best intake time of resveratrol, pterostilbeen, curcumin and quercetin, we need to take into account the process that is being stimulated by these antioxidants. Resveratrol, pterostilbeen, curcumin and quercetin are so-called polyphenols, which are produced by plants to protect themselves from stressors such as viral or bacterial infection. In humans, these antioxidants are known to activate SIRT1. This NAD+ dependent protein, which is important for cellular homeostasis, becomes more active in the body under numerous conditions.

resveratrol sirt1 ampk mtor
When AMPK upregulates SIRT1, mTOR is suppressed.

AMPK activates SIRT1 in times of stress (4), sending a signal to the body that it must protect itself in order to survive these stressors on a cellular level. There are several forms of stress, which ultimately lead SIRT1 expression. One such stressor is a lack of nutrients in the bloodstream, caused by calorie restriction. As such, by consuming fewer calories than one needs to maintain his or his mass, or by implementing periods of fasting, one can stimulate SIRT1 (5). Although other forms of stress also increase SIRT1, calorie restriction appears to be one of the main forces stimulating SIRT1 expression in healthy individuals.

In addition to stimulation by stress factors, SIRT1 is also stimulated by the presence of NAD+. The body can synthesize this coenzyme in several ways. Such as through physical activity like weightlifting. When excercising, NADH is released and recycled into NAD+ (6). In addition, NAD+ can be stimulated by the presence of NAD+ precursors such as niacin, niacinamide or nicotinamide mononucleotide (nmn) (7). Because SIRT1 relies on NAD+ for its deacytelase activities, ultimately resulting in more ATP production in mitochondria, it is useful to combine SIRT1 activators with NAD+ precursors. Our evidence-based formulas make use this synergy.

What do SIRT1 levels look like throughout the day?

The SIRT1 protein is activated under stress. One such stressor is the lack of nutrients. If the body no longer receives nourishment, this is stressful for the body. The body deals with this stress, by using energy for cell protection versus cell growth. For said purpose, damaged cells are converted into energy through a process called autophagy, rather than taken from nutrients in the bloodstream. Owing to this process, people can survive quite a long time without eating anything at all.

Because the body sees calorie restriction or fasting as a major stress factor, SIRT1 values are largely regulated by nutrient availability. Many studies measuring SIRT1 levels are done in rats, as rats can easily be sacrificed after an experiment to accurately measure SIRT1 levels. The DNA sequence of rats is very similar to that of humans, this makes research on rats very suitable to learn more about how processes likely to take place in humans.

In one such study on rats, SIRT1 values were measured in rats following a low-calorie diet for nearly 12 months (8). The experimental group that ate only 60% of the calories consumed by rats in the control group, had significantly higher SIRT1 levels at the end of the experiment. Figure 1. displays SIRT1 levels in the brain, fat tissue, kidney and liver of rats in both the experimental and control group.

After showing that SIRT1 levels are higher in rats that follow a diet that is low in calories, serum of these rats was used in cells derived from humans to test whether or not this would increase SIRT1 levels in human cells.

Serum from both the experimental group (CR), as well as the control group (AL) were used to treat human embryonic kidney cells in vitro. Cells developing after receiving serum from the experimentel group (CR), had SIRT1 levels that were rougly twice as high as in cells receiving serum from the control group (AL).

Figure 1.: SIRT1 levels in the brain, fat tissue, kidney and liver of sacrificed rats. AL = ad libitum, CR = calorie restriction Actin is used both as placebo and control. Source: http://science.sciencemag.org/, 19-08-2020

In other studies, rats were were fed ad libitum for two months (9). After two months, the rats were split into two groups, where the experimental group was limited to drinking water for a time period of 24 hours. The control group had access to food, like they had before. After 24 hours, the livers were removed from the rats in the experiment. Following a 24 hour fast, rats in the experimental group showed SIRT1 levels twice as high as rats in the control group.

We now know that SIRT1 levels are higher when rats are consuming a reduced amount of calories for an extended period of time. We also know that when rats fast for 24 hours, SIRT1 levels are much higher in rats that ate ad libitum. SIRT1 values can therefore be quickly stimulated by fasting, where calorie restriction seems to be a good strategy to activate overall SIRT1 levels in the long term.

SIRT1 12h fast
Figure 2.: The estimated SIRT1 curve for 24 hours, for someone who eats between 08:00 and 20:00.

If the human body reacts to calorie restriction and fasting in the same way as rats, we could predict our SIRT1 values throughout the day. For example, let’s take someone who eats his meals between 08:00 and 20:00. Said person is basically fasting from 20:00 in the evening to 08:00 the next morning. Figure 2 resembles what the SIRT1 curve would look like in such a case, based on what we know from studies done on rats.

When is the best time to take sirt1 activators?

If someone fasts for a longer part of the day, SIRT1 values will reach a higher peak and last longer. The SIRT1 curve for someone eating between 14:00 and 20:00 would then look more like in Figure 3. The same effect can also be achieved by supplementation with a SIRT1 activator such as our very own Strong Heart. In order to make the most of such SIRT1 activating supplement, fasting can be combined with SIRT1 activators to enhance the positive effects of fasting. An estimate of what such a SIRT1 curve would look like can be seen in figure 4.

SIRT1 16h fast
Figure 3.: SIRT1 values reach a higher peak and last longer, if one fasts for a longer period of time throughout the day. The same effect can also be achieved by supplementing a SIRT1 activator such as Strong Heart at breakfast.
SIRT1 16h fast plus resveratrol
Figure 4.: SIRT1 values can be stimulated during fasting, for an enhanced fasting effect.

Elixir Life and SIRT1 activation

SIRT1 uses NAD+ for its deacytelase activities. If NAD+ is readily available, SIRT1 can perform its activities more easily. In addition, NAD+ has been shown to active in SIRT1, by supplementation with a NAD+ precursor such as niacinamide (10). Besides precursors, NAD+ can use others resources too. As such, NADH that is released during physical activity can provide NAD+ with the electrons it needs. One can therefore also expect some SIRT1 activity during the day, through physical exertion. In figures 2, 3 and 4, this phenomena has been included in the curve.

Just as a grapes produce resveratrol in response to viral infection, the human body would activate SIRT1 in response to such a stress factor. So you can expect that exposing the body to all kinds of stressors leads to an increase in SIRT1. Exposing it to such factors can lead to useful cellular adaptations, making the body stronger. However, for such an adaptation to take place, the cell must survive the stressor. This means it’s useful to perform physical excercise one can actually recover from, so that cells can adapt accordingly. On the other hand, running a marathon without proper training, or having a COVID-19 patient coughing all over your face, may not be a good idea. Such a stress factor is probably too much for the immune system to cope with, resulting in cell damage rather than adaptation.

Conclusion

It seems useful to include the intake time as a variable in future research studying the effects of SIRT1 upregulators. 

Based on the scientific evidence available as of writing, we hypothesized that SIRT1 is best stimulated when SIRT1 values naturally reach their peak. This means that the products of Elixir Life are probably best taken in the morning, by most individuals. SIRT1 activators can be consumed with water, at breakfast, allowing the resveratrol to soak in with the nutrients of your meal. Alternatively, stimulate your SIRT1 values during your morning fast to enhance the positive effects of fasting. Resveratrol is best absorbed into the bloodstream, in the presence of other nutrients, especially fatty acids. To increase the bioavailability of resvertrol during a fast, it could be taken in combination with an oil that doesn’t negatively effect your fast, such as MCT C8 oil.

As a fasting mimicant, resveratrol could be taken at night to kickstart your overnight fast. This seems more useful for those fasting in the evening. The best time to use resveratrol is highly dependent on one’s own lifestyle. We hope that the information in this article will help optimize your SIRT1 activator intake time. Still have doubts as to when you had best take our supplements? Feel free to contact us.

Elixir Life and SIRT1

Elixir Life’s formulas are specifically designed to activate SIRT1, with the aim of keeping our cells healthy. Doing our own research allows us to create evidence-based formulas based on the latest scientific findings. This allow us to stay ahead of our competition, both in effectiveness of our supplements and price.

When designing our products, we take in consideration all the flaws of standard products. We use quality ingredients of the highest possible standardization rate for our products. The ingredients used in our formulas are all flawlessly in sync. Allowing you to stack them for a stronger, more diverse effect.

ResveraShield is a great resveratrol supplement for general health and heart health. Bright Mind is our curcumin formula with a twist, designed to make your brain cells more resilient. Strong Heart is our flagship product, our one pill miracle specifically designed to boost the cardiovascular health. Like ResveraShield, it upregulates SIRT1, NAD+ and AMPK.

Literature
  1. Hu, Y., Liu, J., Wang, J., & Liu, Q. (2011). The controversial links among calorie restriction, SIRT1, and resveratrol. Free Radical Biology and Medicine, 51(2), 250-256.

  2. Tillu, D. V., Melemedjian, O. K., Asiedu, M. N., Qu, N., De Felice, M., Dussor, G., & Price, T. J. (2012). Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain. Molecular Pain, 8, 1744-8069.

  3. Jiao, G. E., Yan, L. I. U., Qiang, L. I., Xia, G. U. O., Ling, G. U., Gui, Z., & Zhu, Y. P. (2013). Resveratrol induces apoptosis and autophagy in T-cell acute lymphoblastic leukemia cells by inhibiting Akt/mTOR and activating p38-MAPK. Biomedical and Environmental Sciences, 26(11), 902-911.

  4. Cantó, C., Jiang, L. Q., Deshmukh, A. S., Mataki, C., Coste, A., Lagouge, M., … & Auwerx, J. (2010). Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell metabolism, 11(3), 213-219.

  5. Kanfi, Y., Peshti, V., Gozlan, Y. M., Rathaus, M., Gil, R., & Cohen, H. Y. (2008). Regulation of SIRT1 protein levels by nutrient availability. FEBS letters, 582(16), 2417-2423.

  6. Jang, S. Y., Kang, H. T., & Hwang, E. S. (2012). Nicotinamide-induced mitophagy event mediated by high NAD+/NADH ratio and SIRT1 protein activation. Journal of Biological Chemistry, 287(23), 19304-19314.

  7. Grolla, A. A., Miggiano, R., Di Marino, D., Bianchi, M., Gori, A., Orsomando, G., … & Angeletti, C. (2020). A nicotinamide phosphoribosyltransferase–GAPDH interaction sustains the stress-induced NMN/NAD+ salvage pathway in the nucleus. Journal of Biological Chemistry, 295(11), 3635-3651.

  8. Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., … & Sinclair, D. A. (2004). Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. science, 305(5682), 390-392.

  9. Hayashida, S., Arimoto, A., Kuramoto, Y., Kozako, T., Honda, S. I., Shimeno, H., & Soeda, S. (2010). Fasting promotes the expression of SIRT1, an NAD+-dependent protein deacetylase, via activation of PPARα in mice. Molecular and cellular biochemistry, 339(1-2), 285-292.

  10. Shen, C., Dou, X., Ma, Y., Ma, W., Li, S., & Song, Z. (2017). Nicotinamide protects hepatocytes against palmitate-induced lipotoxicity via SIRT1-dependent autophagy induction. Nutrition Research, 40, 40-47.

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