9 Pterostilbene Health Benefits + Dosage & Side Effects

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They say it’s better than resveratrol. They call it dragon’s blood, or even the fountain of youth. Does science back up the hype? What are the limitations and risks? Find out here.

What is Pterostilbene?

Pterostilbene is an antioxidant found in many plants, including almonds, grape leaves and vines, blueberries and related Vaccinium berries, peanuts, dracaena plants, and Indian kino. Blueberries are the richest dietary source of pterostilbene; some trees produce it in “dragon’s blood,” a red resin with a long history of traditional use [1, 2, 3, 4, 5, 6, 7].

Some supplements are labeled with “trans-pterostilbene” rather than just “pterostilbene.” This compound actually has many names, one of which is trans-3,5-dimethoxy-4′-hydroxystilbene [8].

In chemistry, the word “trans” tells us that certain atoms (or groups of atoms) are on opposite sides of a molecule’s physical structure. The word “cis” tells us that those atoms are on the same side of the molecule. Both trans-pterostilbene and cis-pterostilbene are found in nature, though the trans form is more stable [8, 9, 10].

The word pterostilbene alone, without a modifier, refers to the trans form by default. The cis form will always be called cis-pterostilbene [11, 12].

Pterostilbene is part of a class of compounds called phytoalexins: in plants, these compounds defend against microbes and parasites. It is very similar to a better-known phytoalexin antioxidant, resveratrol. However, pterostilbene is about four times easier to absorb from the gut into the body; in theory, that could make it multiple times more effective than resveratrol, but this has yet to be confirmed in any formal study [13, 14, 15].

Proponents:

• May support weight loss
• May improve cognition
• May help control blood sugar & blood pressure
• Antioxidant benefits to liver, heart, and eyes
• More bioavailable than resveratrol

Skeptics:

• May increase LDL cholesterol
• Drug interactions possible
• Very limited human research
• Significant risk of bias in clinical studies

Pterostilbene has produced positive results for weight loss in at least one study, but larger and more robust studies are required to confirm its effectiveness.

Furthermore, the FDA has not approved pterostilbene for any medical purpose or health claim, and there is no guarantee of the quality of any given supplement. Talk to your doctor before supplementing with pterostilbene.

In a study of middle-aged people with high cholesterol, those who were not taking cholesterol medication lost a small, but significant, amount of weight while supplementing with pterostilbene. This result was somewhat surprising, as this study was not designed to measure pterostilbene as a weight loss aid. This result has not yet been investigated in a separate study [16].

Cell and animal studies also suggest that pterostilbene may help improve insulin sensitivity. Pterostilbene blocks the conversion of sugars into fats and prevents fat cells from multiplying [17, 18].

Pterostilbene may also change the composition of the gut flora, the colonies of microbes that live in the intestine and help digest food.

Rats fed pterostilbene had healthier gut flora, including a significant increase in Akkermansia muciniphila, a species of bacteria that appears to prevent obesity, diabetes, and low-grade inflammation. A. muciniphila has recently become a focus of probiotic research; future studies will clarify whether and how pterostilbene supports its growth [19, 20, 21].

No clinical evidence supports the use of pterostilbene for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

In mice, pterostilbene reduced anxiety and improved mood. In a study of aged rats, a diet high in pterostilbene increased dopamine and improved cognition. Furthermore, when high levels of pterostilbene were present in the hippocampus of the rats’ brains, their working memory improved [22, 23].

In another rat study, pterostilbene also promoted the growth of new cells in the hippocampus, the emotion and memory center of the brain. Plus, when stem cells from young rat brains were exposed to pterostilbene, they grew faster [24].

This same rat study found that pterostilbene was a more powerful antioxidant than its close relative resveratrol. Multiple studies have confirmed that pterostilbene protects against oxidative stress in brain cells [23, 25].

According to cell research, pterostilbene blocks monoamine oxidase B (MAO-B) and increases available dopamine in the brain. This mechanism is similar to Parkinson’s disease medication like selegiline, rasagiline, and safinamide [26, 27, 28].

In a cell study, pterostilbene also protected neurons against a specific type of damage associated with Alzheimer’s disease [29].

Multiple animal studies suggest that pterostilbene may increase insulin production and thereby decrease blood sugar.

In diabetic mice, pterostilbene protected the pancreas from damage and restored the production of sugar-metabolism enzymes in the liver. These effects are strong enough that some researchers compared pterostilbene to metformin, a diabetes medication [30, 31, 32].

However, researchers disagree on whether these effects translate to humans.

One safety study on people with high cholesterol found no significant difference in blood sugar between up to 250 mg/day of pterostilbene and the placebo. No human studies have specifically focused on the interaction between pterostilbene and blood glucose. More research is likely to emerge in the coming years [14].

In a rat study, pterostilbene significantly improved the symptoms and cellular markers of severe acute pancreatitis, a disease caused by pancreas inflammation. In people, this disease can cause many complications, including death, and there is no reliable treatment. Pterostilbene may support people suffering from severe acute pancreatitis and improve survival rates [33, 34].

Some other studies have suggested that pterostilbene is only a weak anti-inflammatory with no useful effect on edema or arthritis. More research is required to understand whether pterostilbene is useful as an anti-inflammatory compound [35, 36].

Pterostilbene protects liver cells from oxidative stress and may even restore some function in damaged liver tissues. In multiple animal studies, pterostilbene prevented scarring (or fibrosis) and inflammatory damage in the liver [1, 37, 38].

Over-exposure to acetaminophen (also known as paracetamol or Tylenol) is one of the most common causes of liver damage. In mice, pterostilbene prevented liver damage from acetaminophen exposure [39].

These effects have not yet been studied in humans.

Pulmonary heart disease, or cor pulmonale, is a condition wherein the right side of the heart is enlarged, resulting in an abnormal heartbeat, wheezing, discolored skin, and other symptoms.

In one rat study, pterostilbene restored normal antioxidant balance and reduced symptoms of cor pulmonale in the heart. A cell study supported these findings: heart cells and tissues exposed to pterostilbene had an improved antioxidant response in the face of oxidative damage [40, 41].

Research on pterostilbene and the heart is in its early stages; no studies have investigated its effects on heart disease in people.

The antioxidant properties of pterostilbene may help prevent damage to the eye surface. In one study, pterostilbene protected human corneal cells from oxidative stress; the study’s authors suggested that this compound might help prevent conditions like dry eye [42].

Researchers are also investigating whether pterostilbene may prevent acquired blindness associated with diabetes [43].

The most common claim printed on pterostilbene supplement bottles is that it may prevent age-related disorders and thereby extend lifespan, but human trials have yet to investigate its effects on the markers of aging.

In rats, low doses of pterostilbene improved cognitive symptoms of aging. This study was designed to test “diet-achievable” supplementation, which suggests that eating plenty of pterostilbene-rich foods like blueberries may hold off the cognitive decline of old age [44, 23, 45].

Some researchers have argued that the various mechanisms of pterostilbene may prevent or delay diseases associated with old age like cancer and dementia [46].

The body of research on pterostilbene is much smaller than on resveratrol, even though pterostilbene is likely to be much more potent and bioavailable.

Thus, many pterostilbene studies are small and exploratory, with very few clinical human studies. Many of the advertised benefits of pterostilbene have been extrapolated from animal or cell studies. Clinical studies are likely to emerge in the next few years, and these will clarify the effect of pterostilbene on the human body.

The best-known clinical studies on nicotinamide riboside and pterostilbene in combination were funded by Elysium Health. Elysium manufactures and markets a supplement called Basis which combines these ingredients. Six of the authors of the study are Elysium employees who own shares in the company; the risk of bias is therefore very high.

Researchers have studied pterostilbene’s ability to fight breast, esophageal, stomach, colon, pancreatic, prostate, blood, lung, and skin cancer cells. It has become a hot topic of cancer research in recent years [1, 47, 48].

In rats subjected to UVB radiation (the type of radiation that causes sunburns), a pterostilbene cream on the skin prevented the development of skin cancer. These results were confirmed in cell studies. If these results can be repeated in humans, pterostilbene may be added to sunblock creams as an extra layer of protection [48, 49, 50, 51].

Chemo Combinations

Pterostilbene’s most promising application against cancer may be in combination with other substances. Two cell studies have identified strong interactions between pterostilbene and two other drugs: sertraline (an antidepressant under investigation as a brain cancer drug) and gefitinib [13, 52].

Sertraline is typically used as an antidepressant, but it has demonstrated some activity against glioblastoma brain cancer cells; gefitinib is a more traditional chemotherapy drug. When combined with either of these drugs, pterostilbene blocks the growth of glioblastoma [13, 52].

Pinostilbene

In mice, about half of all dietary pterostilbene has transformed into pinostilbene by the time it reaches the colon. Pinostilbene blocks the growth of human colon cancer cells, suggesting that pterostilbene supplementation may be useful against colon cancer [53].

Possible Mechanism of Action

Pterostilbene fights oxidative stress by rebalancing antioxidant enzymes. In cells, it increases superoxide dismutase 1 (SOD1) and peroxiredoxin-4 (PRDX4), which bind to reactive oxygen species. Researchers have observed this effect in human eye cells, suggesting that pterostilbene may protect from oxidative damage [42].

Sirtuin Activation

You may have seen commercial pterostilbene products with “sirtuin activator” written in large, bold lettering on the bottle. Some of these products even claim that sirtuin is a fountain of youth, but the truth is more complicated.

In cells, pterostilbene activates a SIRT1 signaling pathway that protects against cellular damage. This pathway increases the expression of p53, a protein that protects the DNA and prevents mutations that could lead to cancer [54, 55].

SIRT1 may protect against some of the degeneration and damage that takes place as we grow old. However, pterostilbene is not a magic pill against aging [56].

Multiple studies have demonstrated that pterostilbene decreases inflammation regulated by tumor necrosis factor-alpha (TNF-alpha). Oxidative stress causes inflammation; pterostilbene may block TNF-alpha and interleukin-1b (IL-1b) by reducing reactive oxygen species [33, 57, 58].

Pterostilbene also prevents stress within a part of the cellular machinery called the endoplasmic reticulum, or ER. In one study, when cells from the lining of blood vessels were exposed to pterostilbene, their ER did not respond to inflammatory signals, and they did not become inflamed [57].

Strangely, despite decreasing endoplasmic reticulum stress in the blood vessel lining, pterostilbene actually increases ER stress in throat cancer cells. It may protect healthy cells and selectively damage cancerous cells [59].

In glioma (brain or spinal cancer) cells, pterostilbene decreased Bcl-2 and increased Bax; these changes increase cell “suicide” signals and cause glioma cells to die off [47].

Cancer cells use a pathway called Notch-1 to protect themselves from chemotherapy drugs, including oxaliplatin and fluorouracil. Pterostilbene appears to block Notch-1 signaling; it could, therefore, make tumors more sensitive to conventional chemotherapy [60, 61].

In lung cancer cells, pterostilbene decreased the production of various cancer-promoting compounds (MUC1, NF-κB, CD133, b-catenin, and Sox2). Altogether, these effects reduce inflammation and make it much more difficult for cancer cells to grow [62].

Pterostilbene appears to selectively target the hippocampus region in the brain. There, it increases brain-derived neurotrophic factor (BDNF), mitogen-activated protein kinases (MAPK), and cAMP response element binding protein (CREB) [24, 63, 64].

These three proteins help neurons grow, multiply, and respond to their surroundings. SNRI antidepressants often target these pathways as well.

Also in the hippocampus, pterostilbene increases a protein called Nrf2, which in turn increases the expression of antioxidant proteins [25].

The monoamine oxidases, MAOs, are enzymes that break down neurotransmitters in the brain. One of these enzymes, MAO-B, selectively breaks down dopamine; as a result, drugs that block MAO-B increase dopamine in the brain. According to a recent animal study, pterostilbene inhibits MAO-B activity and, thus, increases available dopamine [65, 66, 26].

Finally, pterostilbene may prevent Alzheimer’s disease by protecting the brain from beta-amyloid (Aβ). The precise pathway is unknown, but it appears to involve PI3K and Akt, two proteins that support memory, learning, and neuron growth [29, 67].

Side Effects & Precautions

Pterostilbene is considered safe and has no significant side effects up to a dose of 250 mg per day. Some people may have increased LDL cholesterol when taking pterostilbene; grape seed extract negates this effect and may pair well with a pterostilbene supplement [68, 14].

There are currently no studies on the safety of pterostilbene for children or for pregnant or breastfeeding women. Because this compound is commonly found in food and considered to be healthy, small doses of pterostilbene should be safe for anyone; however, caution is advised at higher doses.

Talk to your doctor before giving pterostilbene to children or taking it yourself if you are pregnant or breastfeeding.

Two studies have confirmed that pterostilbene may increase the effect of sertraline and gefitinib. Sertraline is a selective serotonin reuptake inhibitor (SSRI) which is used to treat depression; gefitinib is an epidermal growth factor receptor (EGFR) inhibitor which is used in chemotherapy. The combinations of pterostilbene with either sertraline or gefitinib have been studied for their anticancer effects [52, 13].

Pterostilbene also appears to block the activity of several metabolic enzymes, most notably CYP2C8 and UGT1A6 and will increase the effect of any drug they metabolize. For CYP2C8, these include the antimalarial drug amodiaquine, cerivastatin, repaglinide, torasemide, and a few chemotherapy drugs. For UGT1A6, these include acetaminophen and aspirin [69, 70, 71].

Very few studies have investigated how pterostilbene interacts with medication. However, it increases the effect of sertraline, blocks drug metabolism enzymes, and is likely to have other unstudied interactions.

To avoid adverse events and unexpected interactions, talk to your doctor before supplementing with pterostilbene.

Supplement Forms & Dosage

Pterostilbene is most commonly sold in capsules, with a variety of dosages available.

Carefully read the label and check the amount of pterostilbene per capsule before buying, as different dosages may have different effects. Furthermore, some commercial supplement dosages are higher than what has been studied in humans. Readily available dosages range from 50 mg to 1,000 mg per capsule.

Combination supplements are also available. The most common combination is pterostilbene with resveratrol; you may also see it combined with astragalus, curcumin, green tea, and other compounds.

In some parts of the world, you may also be able to find sunblock creams that contain pterostilbene. The percentage content of pterostilbene required to effectively prevent skin cancer is unknown, but it may provide some extra protection.

Dragon’s blood is the common name for a red resin from Dracaena trees and a few other genera of plants. It is a part of traditional medicine in East and Southeast Asia; practitioners used it to support many aspects of health. Its active ingredient is pterostilbene [72, 7, 24].

Extracts of dragon’s blood are commercially available as tinctures, capsules, and skin creams. Note that these extracts may contain other bioactive compounds besides pterostilbene. No safety data is available for dragon’s blood extracts.

There is no safe and effective dose of pterostilbene because no sufficiently powered study has been conducted to find one. Furthermore, clinical trials are sorely lacking, so there’s little data to draw from regarding doses that have had positive effects.

In humans, doses of up to 250 mg per day are considered safe. Higher doses such as these have been demonstrated to reduce blood pressure and possibly promote weight loss. LDL cholesterol levels increased significantly as well, but this effect was completely negated with the addition of grape seed extract [14, 16].

In animals, much lower doses have had cognitive effects. Between 1 and 2 mg per kg of body weight per day reduced anxiety in mice [73].

If you are taking pterostilbene for its cognitive benefits, you may wish to start with a very low dose. However, such low-dose effects have only been observed in mice thus far, and these quantities may have no effect whatsoever on humans.

The combination supplement of nicotinamide riboside and pterostilbene (NRPT) has been found to produce benefits at a dose of 500 mg of nicotinamide riboside and 100 mg of pterostilbene per day [74].

Combination supplements of nicotinamide riboside and pterostilbene claim to extend your lifespan by boosting NAD+ levels in the blood. But do they work?

Nicotinamide riboside is a compound found in milk. It is closely related to vitamin B3 and can be converted into nicotinamide adenine dinucleotide, or NAD+, in the body [75].

NAD+, meanwhile, is an important player in metabolism, making new proteins, and repairing DNA. NAD+ levels decrease as we get older. Some researchers believe that consuming NAD+ precursors may help us live longer [76].

In one clinical study, a group of people aged 60 – 80 years old took nicotinamide riboside with pterostilbene (NRPT) once daily, twice daily, or not at all for several weeks. By the end of the trial, those who had taken the supplement twice a day saw their NAD levels nearly double, with no reported side effects. However, this study was funded by the manufacturer of the NRPT supplement and is therefore at high risk of bias [74].

Pterostilbene is an antioxidant compound found in blueberries, almonds, peanuts, grape leaves, and some trees. It is closely related to resveratrol, but is more easy to absorb from the gut into the body. Supplement producers claim that it can improve cognition and reduce the markers of aging, but clinical research is sparse.

Pterostilbene is very safe, though large doses may increase LDL cholesterol. Combine it with grape seed extract to prevent this side effect.

Pterostilbene interacts with sertraline and gefitinib, and it may also increase the effects of acetaminophen, aspirin, and other drugs. If you are on medication, talk to your doctor before supplementing with pterostilbene.

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