Exercise? What for?
Unpacking the effects of nutraceuticals in tandem with exercise
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I know that nutraceuticals like resveratrol have the possibility to improve my vascular health. If this were so, and if I were to take these drugs, is there even a need for me to exercise anymore?
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Uncovering the mystery
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What are Nutraceuticals?
A short recap for you
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A Brief Summary
Nutraceuticals is a term derived from the words “nutrition” and “pharmaceuticals". [1] The term makes reference to nutritional supplements (nutrients) that bear dietary ingredients which could include minerals, vitamins, amino acids or metabolites among others. These products are then consumed with the aim of fulfilling health benefits other than nutrition. [2]
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Resveratrol
One of the nutraceuticals of interest that we will be focusing on is resveratrol, a phenolic substance presenting grapes and wine, as well as in peanuts, soy, berries, and Itadori tea. [3] Resveratrol has been used in Chinese medicine for hundreds of years and is currently being touted as a health-enhancing nutritional supplement in the western world. It is especially well-known for its anti-oxidative properties as well as its potential anti-ageing effects.
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Resveratrol and the Vascular System
Resveratrol in particular has drawn attention from researchers for its potential to retard the effects of ageing in the vascular system, with the range of observed benefits including an increased vasoactivity and an increased antioxidant capacity. [4]
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Nutraceuticals & Exercise
Defining the relationship
Resveratrol has been reported to improve vascular health in ageing models in two major ways. The first is via the improvement of the vasoactive balance which is mainly achieved via the increased availability of vasodilatory factors such as NO, in the blood. [5] This then works to improve the endothelial function in blood vessels which have suffered from a decrease in the vasoactive balance due to the ageing process. The second way in which resveratrol works to reverse vascular ageing is through the relief of oxidative stress via the lowered expression enzymes that produce superoxides and the heightened expression of antioxidant enzymes. [6] ,[7]
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What is noteworthy here is that exercise has similar effects on vascular ageing. Both resveratrol and exercise have been observed to regulate similar molecular pathways and enzymes [8] that eventually lead to similar protective effects from the negative health impacts of ageing. [4]
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In essence, by mimicking the cellular signalling of exercise, resveratrol has been proposed to reduce endothelial function and oxidative stress, supplementing the positive health benefits of exercise.
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Pit Stop:
A quick FYI on the role of oxidative and nitrative stress in vascular ageing
As we grow older, there is an increase in oxidative stress in our blood vessels due to the production of reactive oxygen species. This is responsible for certain cytotoxic effects, impairment of mitochondrial function and activation of inflammation.
There is also a decrease in the bioavailability of nitric oxide (NO) in our blood that results in the decreased ability of the endothelium of our blood vessels to dilate and the increase in vasoconstriction and arterial stiffening.
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These negative impacts of ageing on our vascular health are what we will be trying to target here today.
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If resveratrol can mimic the downstream vascular effects of exercise, does this mean that there is no need for me to exercise anymore if I were to consume these nutraceuticals?
Oh no, not so fast. Given that resveratrol has similar benefits as what has been described for exercise training, it has been hypothesised that there is a possible induction of synergistic health-enhancing effect in ageing individuals if both exercise training and resveratrol were supplemented in tandem. [4] The combination could have an additive effect.
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This would mean that in order to maximise anti-ageing benefits to one's health, exercise would still be required on top of dietary supplementation...
Are there any studies to show that such an effect between resveratrol, exercise and vascular health exists?
Optimistic results
…the exercise-mimicking effects of resveratrol observed in rat models indeed stemmed from the fact that resveratrol activated the same protein pathways and molecular mechanisms in our body as what is observed when we exercise. [8]
Furthermore, what is promising is that this study found that when resveratrol treatment was administered in tandem with exercise training, the activation of these molecular mechanisms were greatly enhanced as compared to when resveratrol treatment or exercise training was carried out independently. [8]
This observation in animal models indeed provides us with optimistic results as it suggests there is some synergistic or additive effect in our body when resveratrol is supplemented with exercise.
These results are especially significant since the molecular pathways suggested in this study have been implicated in the downstream improvement of 2 main negative effects of vascular ageing: the decrease in vasodilatory function and the increase in oxidative stress. [4]
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In this study, it was investigated whether 12 weeks of treadmill exercise training and/or resveratrol could enhance the performance of high capacity runner rats. [5] These rats were bred specifically for their treadmill endurance running capacity in order to explore the aerobic biology-disease connection. [5]
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The study observed resveratrol’s enhancement of the exercise-dependent activation of the AMPK-SIRT1-PGC-1a pathway and it was found that resveratrol activated the AMP-activated protein kinase, SIRT1.
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While trials were mainly concerned with the enhancement of aerobic activity in muscle cells through these pathways, the same proteins have been shown to be mediated in the vascular system, which points us to the possibility that the combination of resveratrol and exercise would have the same effect there.
Well, a 2013 pre-clinical study showed that...
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Hover for more info
Okay, so it’s confirmed then that we need to exercise while taking resveratrol?
Well, this study was done primarily in aged males from 60-72, so the conclusions drawn from this subgroup is quite small. In addition, it has a rather low sample size of 27 subjects. However, resveratrol use and it’s relation to exercise is a field of research that has not been fully explored yet, and hence information about the effects of resveratrol on other subgroups, such as younger people, is hard to discuss. As such, until more information is shed regarding any possible synergistic effect between resveratrol and exercise, we would recommend not to draw any conclusions!
The study found that Low-Density Lipoprotein (LDL), or ‘bad cholesterol’, was only lower in the group that took the placebo but not those that took resveratrol (6)! This was also found to be the case in terms of blood pressure. In both cases however, it must be highlighted that resveratrol use did not increase these measured markers of vascular ageing. Resveratrol use was also not found to slow the onset of atherosclerosis. This indicates that there might be some conflict with the effects of Resveratrol and exercise, particularly if the exercise was done at high intensity. This study hence suggests that resveratrol use may not be a particularly useful supplement if you hope to help delay vascular ageing through exercise.
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Clinical Trials
How does resveratrol and exercise effect humans?
Well, trials in Humans have shown some interesting results too. Clinical trials in older humans have shown that Resveratrol supplementation blunts the positive effects of exercise, namely reduced blood pressure and blood cholesterol [9]. In this study, a group of 27 men from 60 – 72 were subjected to a double-blinded placebo-controlled trial, where they were made to exercise for 8 weeks under the effects of resveratrol or a placebo.
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Based on this study, it seems that resveratrol use in humans, at least amongst aged males, does not seem to boost the positive health effects of exercise. It might seem a little strange considering what was found in the mice studies, but there could be legitimate reasons for this!
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What are the
limitations of
the study?
What were
the findings?
So there is conflicting evidence with regards to animal studies and human trials? What is the reason for such differences?
Why so different?
Aren't these animal trials supposed to be good models? Why are they showing opposite results?
While it is true that animal trials are carried out due to ethical complications in carrying out certain experiments in humans, it does not mean that the results obtained in these trials will always be reproducible in human trials as well. If that were the case, why bother with clinical trials at all? The mechanistic explanation of the difference in response to resveratrol in humans and mice with regards to exercise is currently still not fully understood, but this is to be expected, as there are differences in cardiovascular function, drug metabolism and metabolism in the two species for such results to not be surprising [10].
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Once such reason suggested is the difference in response in humans and mice in Sirturin 1 (SIRT1) levels. This protein is linked with reduction in oxidative stress and reduction in inflammation, and resveratrol use does not seem to increase SIRT1 levels as predicted by mice studies [11].
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Conclusions...
In short: Yes. The possible synergy between Resveratrol and exercise in improving vascular health is yet to be fully explained by science, so it is currently safe to assume that Resveratrol does not help you reduce the amount you need to exercise.
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The effects of Resveratrol by itself on our vascular health is still not fully conclusive, and hence to speak definitively on the effects of both Resveratrol and exercise is something that is extremely hard to do. Exercise by itself, however, has been thoroughly researched and proven to improve one’s vascular health, so there is no need to avoid it!
What now?
Our recommendations
There is generally no need to take resveratrol in supplementary form, but it is also not necessary to avoid it altogether if it is present in foods in your diet. Moderation should be exercised, as with all forms of nutraceuticals.
This attitude of moderation is also something that should be exercised in your exercise! Too little exercise would decrease your vascular health, but at the same time, the detriment of over-exercise is ever-present. If you exercise a healthy amount, your vascular health will certainly improve.
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Done by: Amirah and Imran
References
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Kan, N., Lee, M., Tung, Y., Chiu, C., Huang, C., & Huang, W. (2018). The synergistic effects of Resveratrol combined with resistant training on exercise performance and physiological adaption. Nutrients, 10(10), 1360. https://doi.org/10.3390/nu10101360
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Nasri, H., Baradaran, A., Shirzad, H., & Rafieian-Kopaei, M. (2014). New concepts in nutraceuticals as alternative for pharmaceuticals. International journal of preventive medicine, 5(12), 1487–1499.
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Salehi, B., Mishra, A. P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P., Martins, N., & Sharifi-Rad, J. (2018). Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines, 6(3), 91. https://doi.org/10.3390/biomedicines6030091
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Gliemann, L., Nyberg, M., & Hellsten, Y. (2016). Effects of exercise training and resveratrol on vascular health in aging. Free radical biology & medicine, 98, 165–176. https://doi.org/10.1016/j.freeradbiomed.2016.03.037
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Schmitt, C. A., Heiss, E. H., & Dirsch, V. M. (2010). Effect of resveratrol on endothelial cell function: Molecular mechanisms. BioFactors (Oxford, England), 36(5), 342–349. https://doi.org/10.1002/biof.109
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Robb, E. L., & Stuart, J. A. (2011). Resveratrol interacts with estrogen receptor-β to inhibit cell replicative growth and enhance stress resistance by upregulating mitochondrial superoxide dismutase. Free radical biology & medicine, 50(7), 821–831. https://doi.org/10.1016/j.freeradbiomed.2010.12.038
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Gambini, J., Inglés, M., Olaso, G., Lopez-Grueso, R., Bonet-Costa, V., Gimeno-Mallench, L., Mas-Bargues, C., Abdelaziz, K. M., Gomez-Cabrera, M. C., Vina, J., & Borras, C. (2015). Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans. Oxidative medicine and cellular longevity, 2015, 837042. https://doi.org/10.1155/2015/837042
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Hart, N., Sarga, L., Csende, Z., Koltai, E., Koch, L. G., Britton, S. L., Davies, K. J., Kouretas, D., Wessner, B., & Radak, Z. (2013). Resveratrol enhances exercise training responses in rats selectively bred for high running performance. Food and Chemical Toxicology, 61, 53-59. https://doi.org/10.1016/j.fct.2013.01.051
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Gliemann, Lasse, Jakob Friis Schmidt, Jesper Olesen, Rasmus Sjørup Biensø, Sebastian Louis Peronard, Simon Udsen Grandjean, Stefan Peter Mortensen, et al. “Resveratrol Blunts the Positive Effects of Exercise Training on Cardiovascular Health in Aged Men.” The Journal of Physiology 591, no. 20 (2013): 5047–5059.
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Gliemann, Lasse, Michael Nyberg, and Ylva Hellsten. “Effects of Exercise Training and Resveratrol on Vascular Health in Aging.” Free Radical Biology and Medicine 98. Human Performance and Redox Signaling in Health and Disease (September 1, 2016): 165–176.
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Skrobuk, P., S. von Kraemer, M. M. Semenova, A. Zitting, and H. A. Koistinen. “Acute Exposure to Resveratrol Inhibits AMPK Activity in Human Skeletal Muscle Cells.” Diabetologia 55, no. 11 (November 1, 2012): 3051–3060.