Resveratrol with Pterostilbene
Resveratrol with Pterostilbene

Resveratrol With Pterostilbene 

Resveratrol and pterostilbene supplements are often taken for their supposed brain boosting benefits, but they are also associated with improved energy endurance, promoting a healthy inflammatory response, support of healthy blood glucose levels, and promoting healthy aging and youthfulness, supporting against DNA damage and cell damage, weight-control, and with having cardiovascular benefits. 

Pterostilbene is chemically related to resveratrol. They differing only at their methoxy and hydroxy groups. Although they are both antioxidants it is thought that their benefits relating to healthy aging are due to other mechanisms.

Of the two molecules, the vast majority of lab research has been performed on resveratrol, largely because it is a key component of wine. It is able to indirectly activate sirtuins messengers [1], which are themselves induced during fasting and are associated with longevity. It has also been shown to have positive effects in the support of healthy blood flow, inflammation, insulin sensitivity, and of the heart.

More recently, many researchers have focused their effects on understanding pterostilbene, which itself is a derivative of resveratrol, but has better absorption levels and greater antioxidant potency; it has been linked to promoting healthy cognition and supporting healthy glucose and cholesterol levels. 

There is presently much more known about how resveratrol works, so although the supplement has already been shown to have many desirable aspects it is more usual to take resveratrol with pterostilbene in the world of nootropics. 

A look at Resveratrol 

The stilbenoid resveratrol (3,5,4′-trihydroxy-trans-stilbene) is naturally found in grapes, and its presence as one of the key antioxidative components of wine has made it of great interest. For those of you who may not know, wine is strongly associated with good health in France and Spain, and is thought to be one of the main reasons why the French people generally have a healthy heart despite consuming a rich diet (the French Paradox). It is a natural phenol phytoalexin acting to protect grapes from infection by the necrotrophic fungus Botrytis cinerea. 

Because of its presence in wine [2], the compound is often referred to as red wine extract, but in addition to wines it is also found in blueberries, mulberries, lingonberries/partridgeberries, raspberries, and in plants belonging to the Senna genus.

Positive Effects of Resveratrol 

• Supporting healthy Blood Flow 

General Blood Flow has been shown to increase at low dosages of resveratrol and cerebral blood flow (with no associated mental fatigue) and oxygen at larger doses [3]. 

With regards to general cardioprotective effects, prolonged supplementation with resveratrol has been shown to lead to support healthy endothelial function, left ventricular diastolic function, and levels of LDL-cholesterol [4].

Trans-resveratrol administered orally as single doses of 250 mg and 500 mg was found to support cerebral blood flow and hemodynamics (differences in oxygenation of hemoglobin) after 45 minutes of absorption in a dose dependent manner. These randomized trials were performed on 22 healthy human beings given cognitive tasks to perform that affected the frontal cortex [3].

• Blood Glucose and Blood Pressure 

In trials performed in overweight men over a 30 day period, which was designed to look at the calorie restriction effects of supplementation with resveratrol, it was found to support healthy blood pressure and blood glucose levels.

In addition to the beneficial blood aspects, the authors also reported that daily supplementation supported healthy resting metabolic rates and a more restful sleep, induced the activity of citrate synthase in the mitochondria, and activated PGC-1α, AMPK, and SIRT1 proteins. They concluded that the daily supplementation had similar biological effects to that of calorie restriction. 

• Support of healthy Insulin levels and Insulin Sensitivity 

A small trial conducted in 2011 showed resveratrol was able to support healthy insulin and glucose levels in obese people [5, 6].

Furthermore, inhibition of adipogenic differentiation and preadipocyte proliferation occurs in a Sirt1 dependent manner. The authors put forward that the induction of intracellular pathways by resveratrol may one day act as a target in the treatment of obesity related endocrine and metabolic effects.

• Fighting Noncystic Acne

When applied topically to the face, resveratrol cream may help to support against non-cystic acne. There may also be a significant reduction in lesions.

• Enhancement of Melatonin neuroprotective effects

The hormone Melatonin is involved in circadian rhythm entrainment and therefore plays a major role in the timing of the sleep-wake pattern, seasonal reproduction, and blood pressure regulation. Melatonin is able to enhance the induction of Heme-Oxygenase 1 by resveratrol in neurons [7]. 

The synergy between the two does not increase mRNA levels, but does inhibit the ubiquitin-proteasome pathway. Furthermore, this synergy between these two components leads to enhancements of anti-oxidative properties and neuroprotection effects. 

• Neurology and Cognition

As mentioned above, resveratrol can cross the blood-brain barrier and is able to support the human cerebral blood flow [4-CHANGE pos]. It is also thought to suppress the release of glutamate in the neurons, thus playing a role in the control of glutaminergic signaling [8].

Some of the neuroprotective effects linked with resveratrol includes overcoming excitotoxicity effects (such as ammonia activated by oxidative stress and nitric oxide production)[9] in morphine tolerant mice through suppression of PSD-95 expression [10].

• Healthy Aging

Most of the research into healthy aging has been performed in the model species Drosophilia and C.Elegans.

There is a body of evidence that resveratrol supports healthy aging in these organisms through up-regulation of Juvenile Hormone. It should be noted that this exact hormone is not present in mammals. So any healthy aging effects associated with resveratrol are resultant from another mechanism(s).

In mammals, resveratrol has been shown to support many noticeable effects related to aging such as cognition, bone mass, and muscle mass as one ages [11]. 

• Cardiovascular Health

As resveratrol is a direct free radical scavenger it is expected to be beneficial in preserving the endothelium from the impact of vasorelaxation agents such as acetylcholine and nitric oxide [12]. 

It has also been shown to be beneficial for relaxation of the arteries [13]. Hypertensive rats provided with the equivalent resveratrol supplementation as found in glasses of wine were found to have increased levels of acetylcholine-induced maximal vasorelaxation. 

As mentioned previously, supplementation may also have health benefits with regards to blood pressure. 

• Weight Management

Due to the way that resveratrol interacts with cell cycles it is expected to have beneficial long-term effects in managing healthy weight. 

It is thought to benefit both muscle and bone health through interfering with the conversion of mesenchymal cells into adipocytes during fat metabolism, this allows stem cells to be used in much more beneficial ways, e.g, for the creation of muscle and bone cells [14].

Resveratrol Synergism With Other Nutrients and With Hormones

In addition to its synergy with melatonin, resveratrol has been reported as having nutrient to nutrient interactions with the flavonoid Genistein (supporting apoptosis during fat metabolism [15]), Vitamin D (bone metabolism, redirection of stem cells), Quercetin (protects blood vessels), curcumin, D-Glucaro-1,4-Lactone, Indole-3-Carbinol, Grape Seed Extract, and β-1,3-Glucan.

Resveratrol has also been shown to have effects on hormonal estrogen metabolism and on testosterone [16]. 

A look at Pterostilbene 

The powerful antioxidant pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) has a very similar structure to resveratrol but is thought to be much more bioavailable and more potent as an antioxidant. 

Some of the health benefits in which it is reported to be beneficial include support of blood glucose levels, cognition, protection against cell damage, reducing oxidative stress, supporting healthy inflammatory response and aging, weight-loss, and enhancement of the cardiovascular system. 

It is naturally present in blueberries (the focus of many of the scientific research studies into it), grape leaves, Pterocarpus, almonds, and peanuts. 

• Healthy Aging

As people get older their cells go through a natural decline in antioxidant activity. Pterostilbene is able to act in the mitochondria (the energy center of the cell) to alter the regulation of numerous genes involved in dealing with oxidative stress conditions [17]. Thus pterostilbene may support healthy aging by promoting cognition and motor function.

NAD+ is involved in the redox reaction in the mitochondria, and therefore plays a major role in the repair of damaged DNA and in cellular metabolism (which are all important processes in the aging process). When 50 mg of pterostilbene was used in combination with 250 mg of nicotinamide riboside (Niagen) there was a benefit in NAD⁺ levels in the blood [18]. 

• Cognition / Brain Health and Function

There have been many neurological health benefits found to be directly related to pterostilbene, these include the control of neuroinflammation, support of healthy mood, and improvements in mental actions through increased levels of it in the hippocampus [19]

• Cardiovascular System

Pterostilbene is linked with supporting healthy blood pressure, activating enzymes with antioxidant roles, and supporting healthy levels of cholesterol and serum triglycerides [20, 21].

• Inflammatory response and immunological Aspects

Ingesting pterostilbene orally is reported to reduce neutrophils oxidation caused by the NADPH oxidase enzyme[22]. This enzyme naturally helps to protect against bacterial invasion but excess levels of it can lead to inflammation-associated injuries. Resveratrol is also an inhibitor of NADPH oxidase.

Further Recommended Published Reading 

• PubMed / Medscape: Mitochondrial Protection by Resveratrol [http://www.medscape.com/viewarticle/745451]
• WebMD: Benefits and Side effects of an all natural treatment [http://www.webmd.com/heart-disease/resveratrol-supplements]
• Wikipedia: [https://en.wikipedia.org/wiki/Resveratrol]
• Reddit: A look at Resveratrol on Examine Per Se[https://www.reddit.com/r/Fitness/comments/srwt5/resveratrol_has_been_preliminarily_completed_at/] 
• Quora questions: What's a sensible dosage for Resveratrol? [https://www.quora.com/Whats-a-sensible-dosage-for-Resveratrol] 

References, Reviews, and Citations

[1] Poulose et al. Effects of pterostilbene and resveratrol on brain and behavior. Neurochem Int. 2015 Oct;89:227-33. doi: 10.1016/j.neuint.2015.07.017

[2] Bertelli and Das. Grapes, wines, resveratrol, and heart health. J Cardiovasc Pharmacol. 2009 Dec;54(6):468-76. doi: 10.1097/FJC.0b013e3181bfaff3.

[3] Kennedy et al. Effects of resveratrol on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Am J Clin Nutr. 2010 Jun;91(6):1590-7. doi: 10.3945/ajcn.2009.28641

[4] Cho et al. Cardiovascular Protective Effects and Clinical Applications of Resveratrol. J Med Food. 2017 Apr;20(4):323-334. doi: 10.1089/jmf.2016.3856.

[5] Baile et al. Effect of resveratrol on fat mobilization. Ann N Y Acad Sci. 2011 Jan;1215:40-7. doi: 10.1111/j.1749-6632.2010.05845.x.

[6] Fischer-Posovszky et al. Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am J Clin Nutr. 2010 Jul;92(1):5-15. doi: 10.3945/ajcn.2009.28435.

[9] Orallo et al. The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption. Mol Pharmacol. 2002 Feb;61(2):294-302.

[10] Friedman et al. Lack of resveratrol neuroprotection in developing rats treated with kainic acid. Neuroscience. 2013 Jan 29;230:39-49. doi: 10.1016/j.neuroscience.2012.10.063.

[11] Bobermin et al. Resveratrol prevents ammonia toxicity in astroglial cells. PLoS One. 2012;7(12):e52164. doi: 10.1371/journal.pone.0052164

[12] Leite et al. Ammonia-induced alteration in S100B secretion in astrocytes is not reverted by creatine addition. Brain Res Bull. 2006 Jun 30;70(2):179-85

[11] Pallauf et al. Resveratrol and Lifespan in Model Organisms. Curr Med Chem. 2016;23(41):4639-4680.

[12] Ku et al. Resveratrol prevents streptozotocin-induced diabetes by inhibiting the apoptosis of pancreatic β-cell and the cleavage of poly (ADP-ribose) polymerase. Endocr J. 2012;59(2):103-9.

[13] Chen et al. Endothelium-dependent and-independent relaxation induced by resveratrol in rat superior mesenteric arteries. Exp Ther Med. 2016 Oct;12(4):2241-2246.

[14] Park et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 2012 Feb 3;148(3):421-33. doi: 10.1016/j.cell.2012.01.017

[15] Vetvicka et al. Glucan and resveratrol complex--possible synergistic effects on immune system. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007 Jun;151(1):41-6.

[16] Gao et al. Disparate in vitro and in vivo antileukemic effects of resveratrol, a natural polyphenolic compound found in grapes. J Nutr. 2002 Jul;132(7):2076-81.

[17] Joseph. Cellular and behavioral effects of stilbene resveratrol analogues: implications for reducing the deleterious effects of aging. J Agric Food Chem. 2008 Nov 26;56(22):10544-51. doi: 10.1021/jf802279h.

[18] ELYSIUM HEALTH Press Release: [https://www.elysiumhealth.com/clinical-trial-press-release]

[19] Al Rahim et al. Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation. Planta Med. 2013 Jun;79(9):723-30. doi: 10.1055/s-0032-1328553 ad.

[20] Rimando et al. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters. J Agric Food Chem. 2005 May 4;53(9):3403-7

[21] Riche et al. Pterostilbene on Metabolic Parameters: A Randomized, Double-Blind, and Placebo-Controlled Trial. Evid Based Complement Alternat Med. 2014; 2014: 459165. doi: 10.1155/2014/459165

[22] Jancinová et al. The combined luminol/isoluminol chemiluminescence method for differentiating between extracellular and intracellular oxidant production by neutrophils. Redox Rep. 2006;11(3):110-6.