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Pterostilbene: Benefits, Side Effects, and Research

Pterostilbene may be a useful supplement for slowing down aging.
Pterostilbene: Benefits, Side Effects, and Research
Date Published: 09/01/2022
Date Modified: 08/26/2023
Pterostilbene may be a useful supplement for slowing down aging.

There are few things as tasty as a good blueberry, but science is showing that there could be more health benefits to this delicious fruit than people might think.

What is Pterostilbene?

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a naturally occurring polyphenol, a type of molecule that occurs in plants. It is part of the stilbene group of compounds and the main antioxidant component of blueberries. In plants, it serves a defensive antimicrobial and often antioxidative role.

It was first discovered in 1977 by Langcake and Pryce and has been studied for its antioxidant properties and potential health benefits [1].

Pterostilbene is chemically related to resveratrol, another popular dietary supplement; some studies suggest that it may be more useful for health than its close relation, sometimes giving rise to the suggestion that it may be a “better resveratrol”.

What foods are high in pterostilbene?

Pterostilbene is found in blueberries, with the estimated content per blueberry varying between 99 ng to 520 ng, depending on the type of blueberry [2-3]. To put this into perspective, an average blueberry punnet weighs around 340 grams.

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If you ate the entire punnet, the total amount of pterostilbene you would get is only 0.03 to 0.18 mg, and based on the dose used in limited human studies of 100mg a day, that would be a huge amount of blueberries a day!

However, if you are looking to naturally obtain the kind of levels of pterostilbene that dietary supplements offer, then you would really, really, need to like blueberries, not to mention the high cost of buying that much fruit. In realistic terms, this is impractical. Supplement dosages range from 50 mg to 1,000 mg per capsule.

Pterostilbene is also found in almonds, grape leaves and vines, cranberries and related Vaccinium berries, such as lingonberries, bilberries, and huckleberries.

Which is better resveratrol or pterostilbene?

Pterostilbene has more bioavailability than resveratrol and other stilbenes due to two methoxy groups, which cause it to exhibit increased lipophilic and oral absorption [4]. In animal studies, pterostilbene was shown to have 80% bioavailability compared to 20% for resveratrol, suggesting that it is a superior choice [5].

So far, the data for pterostilbene looks promising, but it should be noted that it has significantly less research than resveratrol.

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Potential pterostilbene benefits

Various studies have demonstrated the antioxidant, anti-inflammatory [6], and anticarcinogenic properties of pterostilbene, which has led to the improved function of healthy cells and the inhibition of malignant cells [7-9].

Pterostilbene has been implicated in cardiovascular health. with one study showing that it has a protective effect against atherosclerosis [10] and another showing that it improves aspects of autophagy and helps to counteract the pro-atherosclerosis effect of oxidized low-density lipoprotein on vascular endothelial cells [11-12]. It has also demonstrated potential utility in treating ischemia-reperfusion injury [13].

Studies have also shown the potential of pterostilbene in relation to neurodegenerative conditions such as Alzheimer’s disease. A study on mice with accelerated aging showed that pterostilbene, even in low doses, has a significant effect on improving cognitive ability [14].

Another study suggests that pterostilbene is involved in neural plasticity and its associated cognitive and motor functions and that rats given pterostilbene perform better in cognitive tests [15].

Pterostilbene is a powerful anti-inflammatory and can suppress NF-Kb, a protein complex that regulates the transcription of DNA, cytokine production and cell survival [16]. A recent study showed that pterostilbene can potentially treat severe acute pancreatitis by reducing serum levels of inflammatory TNF-a, IL-1b, and NF-kB and that it reduces the generation of reactive oxygen species.

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Pterostilbene also has some data that suggests it might be useful for treating arthritis, and given its anti-inflammatory properties, this is hardly a surprise. While research is limited to date regarding arthritis, a rat study did suggest some potential for treating this condition [17].

Pterostilbene influences energy metabolism

While not unique to pterostilbene but important to mention, pterostilbene activates AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis. AMPK is one of the two catabolic signaling systems, the other being sirtuins; these two work together in a feedback loop and signal nutrient scarcity [18]. These systems are part of our energy metabolism, and deregulation of that system is thought to be one of the reasons we age.

Increasing these two pathways favors health and longevity (on the other hand, the IIS and mTOR pathways reduce lifespan when their levels are increased). In combination, AMPK and sirtuins sense low energy states by detecting high AMP levels and high NAD+ levels, respectively.

AMPK activation has a number of positive effects on metabolism as well as autophagy [19]. It has been shown to influence lifespan in mice that were given metformin. Even better, AMPK even inhibits the mTOR signaling pathway, which increases autophagy [20-21].

Finally, pterostilbene also increases sirtuins, which are best known for their pro-longevity effects in dietary restriction experiments in a variety of animal species [22-23]. Sirtuins adjust cellular metabolism based on nutrient availability and regulate many metabolic functions, including DNA repair, genomic stability, inflammatory response, apoptosis, cell cycle, and mitochondrial functions.

Pterostilbene side effects

Pterostilbene is considered safe, and no adverse effects have been reported up to a dose of 250 mg per day. However, some people may experience increased LDL cholesterol when using it. Given this compound is commonly found in food, dietary levels of pterostilbene should be safe.

That said, pterostilbene has few human studies compared to resveratrol and could potentially interact with other medications in ways not yet known. Caution is advised at the higher doses provided by supplements, as these greatly exceed typical dietary intake. If you do decide to take it and experience any adverse effects, cease taking it immediately and consult your doctor.

Disclaimer

This article is only a very brief summary. It is not intended as an exhaustive guide and is based on the interpretation of research data, which is speculative by nature. This article is not a substitute for consulting your physician about which supplements may or may not be right for you. We do not endorse supplement use or any product or supplement vendor, and all discussion here is for scientific interest.

Literature

[1]  Langcake, P., & Pryce, R. J. (1977). A new class of phytoalexins from grapevines. Cellular and Molecular Life Sciences, 33(2), 151-152.

[2]  Rimando, A. M., Kalt, W., Magee, J. B., Dewey, J., & Ballington, J. R. (2004). Resveratrol, pterostilbene, and piceatannol in vaccinium berries. Journal of agricultural and food chemistry, 52(15), 4713-4719.

[3]  Rodríguez-Bonilla, P., López-Nicolás, J. M., Méndez-Cazorla, L., & García-Carmona, F. (2011). Development of a reversed phase high performance liquid chromatography method based on the use of cyclodextrins as mobile phase additives to determine pterostilbene in blueberries. Journal of Chromatography B, 879(15), 1091-1097.

[4]  Perečko, T., Drábiková, K., Račková, L., Číž, M., Podborská, M., Lojek, A., … & Jančinová, V. (2010). Molecular targets of the natural antioxidant pterostilbene: effect on protein kinase C, caspase-3 and apoptosis in human neutrophils in vitro. Neuroendocrinology Letters, 31(2), 84.

[5]  Kapetanovic, I. M., Muzzio, M., Huang, Z., Thompson, T. N., & McCormick, D. L. (2011). Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer chemotherapy and pharmacology, 68(3), 593-601.

[6]  Choo, Q. Y., Yeo, S. C. M., Ho, P. C., Tanaka, Y., & Lin, H. S. (2014). Pterostilbene surpassed resveratrol for anti-inflammatory application: Potency consideration and pharmacokinetics perspective. Journal of Functional Foods, 11, 352-362.

[7]  Rimando, A. M., Cuendet, M., Desmarchelier, C., Mehta, R. G., Pezzuto, J. M., & Duke, S. O. (2002). Cancer chemopreventive and antioxidant activities of pterostilbene, a naturally occurring analogue of resveratrol. Journal of agricultural and food chemistry, 50(12),

[8]  Remsberg, C. M., Yáñez, J. A., Ohgami, Y., Vega‐Villa, K. R., Rimando, A. M., & Davies, N. M. (2008). Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity. Phytotherapy Research, 22(2), 169-179.

[9]  Kong, Y., Chen, G., Xu, Z., Yang, G., Li, B., Wu, X., … & Chang, G. (2016). Pterostilbene induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma cells. Scientific Reports, 6.

[10] Ekshyyan, V. P., Hebert, V. Y., Khandelwal, A., & Dugas, T. R. (2007). Resveratrol inhibits rat aortic vascular smooth muscle cell proliferation via estrogen receptor dependent nitric oxide production. Journal of cardiovascular pharmacology, 50(1), 83-93.

[11] Zhang, L., Zhou, G., Song, W., Tan, X., Guo, Y., Zhou, B., … & Chen, L. (2012). Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo. Apoptosis, 17(1), 25-36.

[12]  Zhang, L., Cui, L., Zhou, G., Jing, H., Guo, Y., & Sun, W. (2013). Pterostilbene, a natural small-molecular compound, promotes cytoprotective macroautophagy in vascular endothelial cells. The Journal of nutritional biochemistry, 24(5), 903-911.

[13] Guo, Y., Zhang, L., Li, F., Hu, C. P., & Zhang, Z. (2016). Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes. European journal of pharmacology, 776, 26-33.

[14] Chang, J., Rimando, A., Pallas, M., Camins, A., Porquet, D., Reeves, J., … & Casadesus, G. (2012). Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer’s disease. Neurobiology of aging, 33(9), 2062-2071.

[15] Joseph, J. A., Fisher, D. R., Cheng, V., Rimando, A. M., & Shukitt-Hale, B. (2008). Cellular and behavioral effects of stilbene resveratrol analogues: implications for reducing the deleterious effects of aging. Journal of agricultural and food chemistry, 56(22), 10544-10551.

[16]  Pan, M. H., Chang, Y. H., Tsai, M. L., Lai, C. S., Ho, S. Y., Badmaev, V., & Ho, C. T. (2008). Pterostilbene suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Journal of agricultural and food chemistry, 56(16), 7502-7509.

[17] Macickova, T., Drábiková, K., Nosal, R., Bauerová, K., Mihalova, D., Harmatha, J., & Pecivova, J. (2009). In vivo effect of pinosylvin and pterostilbene in the animal model of adjuvant arthritis. Neuro endocrinology letters, 31, 91-95.

[18] Price, N. L., Gomes, A. P., Ling, A. J., Duarte, F. V., Martin-Montalvo, A., North, B. J., … & Hubbard, B. P. (2012). SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell metabolism, 15(5), 675-690.

[19]  Salminen, A., & Kaarniranta, K. (2012). AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing research reviews, 11(2), 230-241.

[20] Mihaylova, M. M., & Shaw, R. J. (2011). The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nature cell biology, 13(9), 1016-1023.

[21]  Kim, J., Kundu, M., Viollet, B., & Guan, K. L. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature cell biology, 13(2), 132-141.

[22] Guo, Y., Zhang, L., Li, F., Hu, C. P., & Zhang, Z. (2016). Restoration of sirt1 function by pterostilbene attenuates hypoxia-reoxygenation injury in cardiomyocytes. European journal of pharmacology, 776, 26-33.

[23] Cheng, Y., Di, S., Fan, C., Cai, L., Gao, C., Jiang, P., … & Li, T. (2016). SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury. Apoptosis, 21(8), 905-916.