Japanese Knotweed

(Polygonum Cuspidatum, Fleeceflower)


Evidence: Very High
Possible Benefits: High
Safety: High

What is Japanese knotweed?

Polygonum cuspidatum, also known as Fleeceflower or Japanese knotweed, is an adaptogenic herb with a long history of use as a traditional medicine. This herb contains high amounts of resveratrol, which may be responsible for most of its benefits and side effects. Contrary to popular belief, resveratrol doesn’t seem to increase lifespan in most people and may even decrease it by hindering exercise performance. This article is about the main benefits of Japanese knotweed, its potential side effects, the best time to take it, and more.

Possible benefits

All of the potential benefits mentioned below are dose-dependent. As with other adaptogenic herbs, there is a sweet-spot dose that allows you to get most of the benefits without causing meaningful side effects or tolerance buildup in the body. We will discuss the best dosing protocol later in this article.

Major benefits

  • Reduced inflammation – 200 mg daily of Japanese knotweed extract standardized to contain 40 mg of resveratrol managed to lower nF-kB activity by 25%. This is a considerable reduction, which is not often seen with other dietary supplements. A decrease in the pro-inflammatory cytokine TNF-α (tumor necrosis factor-alpha) has also been found. This benefit may be due to stilbene or resveratrol.

Minor benefits

  • Improved immune health – Resveratrol was shown in many studies to support innate, adaptive, and mucosal immunity. It can improve cellular intrinsic immune defenses, immune tolerance, immune signaling, and natural killer cell function.
  • Improved blood flow – Low doses of resveratrol were shown to improve blood flow by increasing nitric oxide levels. When higher doses (about 500 mg of resveratrol) are taken, this benefit also applies to cerebral blood flow (blood supply to the brain).
  • Improved blood pressure – Resveratrol can reduce blood pressure in people with hypertension. Blood pressure in healthy people should stay unaffected.
  • Improved brain function – Resveratrol was shown by multiple studies to increase brain-derived neurotrophic factor (BDNF) and improve neural stem cell functions, neurogenesis, HPA axis signaling, executive function, learning and memory, neuroimmune signaling, and more. Whether or not one needs to take higher doses to achieve these effects is not yet known. However, it is certainly possible because increases in cerebral blood flow only seem to apply to doses above 250 mg. The neuroprotective effects also only seem to occur at 20 mg/kg or more.
  • Improved insulin sensitivity – Even very small doses can improve insulin sensitivity to some extent, especially in obese and unhealthy individuals. A small decrease in fasting insulin and blood glucose was also found in one study.
  • Reduced oxidation – Polygonum cuspidatum was able to reduce oxidative biomarkers in one human study. The same applies to resveratrol itself. More evidence is needed to determine the potency and the degree of this effect.
  • Improved cholesterol levels – Resveratrol can improve cholesterol levels but only slightly. It can lower LDL cholesterol but doesn’t impact HDL cholesterol levels much if at all.
  • Reduced acne – Topical application of resveratrol reduced acne by an average of more than 50%.
  • Improved longevity – This benefit does not apply to everyone. In some cases, resveratrol can do the opposite by diminishing the benefits of exercise. If you are active, high doses of resveratrol can indirectly speed up the aging process through this side effect. If you are inactive, the supplement can promote healthy aging and longevity by supporting SIRT1, telomerase activity, stem cells, mTOR signaling, and more. One study on mice on a high-calorie diet directly shows healthspan extension.

Possible side effects

The side effects below are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.

  • Lower exercise adaptations – Resveratrol from Japanese knotweed can lower and sometimes diminish the benefits of exercise, such as increased oxygen capacity and improved cholesterol levels. This is likely caused by mTOR inhibition, which can inhibit muscle protein synthesis. Resveratrol can also lower VO2 max, which is a very important marker for longevity.
  • Reduced anaerobic running capacity – 150 mg of resveratrol taken after a workout was shown to hinder the improvements in anaerobic physical performance in one study. Whether or not this inhibition occurs when one takes resveratrol at other times is not yet clear.
  • Initial adverse reaction – When you start taking Japanese knotweed, things can get worse before they get better. This herb can temporarily worsen some aspects of your health and even make you sick for a few days after you start taking it. That can be unpleasant, but it is usually a sign that the supplement is working and creating a hormetic response that allows the body to adapt and become more resilient in the long term.
  • Allergic reaction – Some people are allergic to this herb and may experience an allergic reaction after they start taking it. Unlike the “initial adverse reaction,” allergic reactions typically don’t disappear until one stops taking the herb.
  • Nausea – This side effect is most common when people take the herb on an empty stomach.
  • Diarrhea – You can usually prevent diarrhea or stomach discomfort by taking this herb with a meal.
  • Toxicity – As an adaptogen, Japanese knotweed acts as a mild stressor on the body. That is usually a great thing as it allows your body to adapt to specific forms of stress and become more resilient. However, stressing the body too much can be counter-productive and cause multiple side effects, including toxicity. While acute toxicity is extremely rare, taking very high amounts of this herb could lead to chronic toxicity and cause health problems over time. To prevent the side effects related to exercise benefit inhibition, staying below 40 mg of resveratrol is best unless you have a great reason to take more.
  • Contamination – If growing or storing conditions are not adequately controlled, Japanese knotweed can be contaminated with bacteria, molds, and other potentially harmful microorganisms. Some growers also use pesticides and herbicides that can be unsafe. Another issue is that herbal supplements can get contaminated with other supplements and chemicals during the manufacturing process. Choose the brand you get herbs and herbal supplements from wisely. It is often best to use websites like Amazon, where thousands of users have reviewed and rated the products. You are less likely to buy something of lower quality there.

Who should not take Japanese knotweed?

You should probably avoid taking Japanese knotweed if you:

  • exercise a lot (resveratrol can greatly inhibit the benefits of exercise, especially when taken close to a workout session)
  • are allergic to this herb
  • experience a severe adverse reaction after taking the herb (though a mild adverse reaction is usually a great thing as it is a sign that the supplement is working and causing a hormetic response that allows the body to adapt and become more resilient)
  • are pregnant or breastfeeding (while it can be safe to take this adaptogen during pregnancy or breastfeeding, it acts as a mild stressor and can put some unnecessary risk to the child)

Who will benefit the most?

You should consider taking the supplement if you:

  • are inactive
  • are planning to take small doses (40 mg of resveratrol or less) that don’t have many side effects

How much Japanese knotweed should you take?

Because Japanese knotweed is an adaptogenic herb, it acts as a mild hormetic stressor on the body, which allows your body to adapt and become more resilient to certain kinds of stressors in the long term.

A higher dose does not necessarily lead to more pronounced benefits. Instead, there appears to be an inverted U-shaped dose-response pattern. In other words, you want to find a sweet-spot dose that allows you to get the benefits of Japanese knotweed without putting too much pressure on the body or quickly causing the body to develop tolerance to the herb.

Japanese knotweed has only been used in a few human studies. In most of the studies, they used 200 mg of an extract standardized for 20% (40 mg) of resveratrol. This dose was shown to be effective.

However, there is much more research on resveratrol itself. Therefore, you may want to consider how much resveratrol to take instead of looking at Japanese knotweed we don’t know as much about.

As little as 10 mg of resveratrol can be effective in some areas, such as for improving insulin sensitivity and cardiovascular health in unhealthy people. Immune signaling can also be improved by low doses.

Higher doses of 250+ mg are better at increasing blood flow, inhibiting aromatase, and supporting brain function, but these extra benefits are usually not worth the side effects.

All things considered, 10-40 mg of resveratrol seems to be the sweet spot dose for most people. Doses higher than this can be more beneficial in some areas but they are also more likely to lower or diminish the benefits of exercise. It’s usually not a good idea to take more than 40 mg unless you are inactive and have a very good reason to take a higher dose.

The higher end of this range usually provides slightly more benefits in the short term. If you plan to take this herb for a longer time (multiple months or years), the lower end is probably a better way to go since you would develop tolerance faster if you were to take higher doses.

While this herb could theoretically cause acute toxicity, you’d need to take an extremely high dose that would be way beyond what even the most potent supplements contain.

Like most other adaptogens, it is best to cycle Japanese knotweed and take about two days off weekly to reset your tolerance. That will allow you to keep getting the benefits in the long term.

Keep in mind that the effects of this herb are cumulative. Therefore, you must take it for at least 2-4 weeks to notice most of the benefits. But again, cycling the herb and not taking it at least twice a week is necessary to prevent tolerance in the long term.

Best time to take Japanese knotweed

Resveratrol is a fat-soluble compound and gets absorbed much better when you take it with food. The same likely applies to many of the other bioactive components of Japanese knotweed.

Whether you take this herb in the morning or the evening typically does not make much difference. Both options are fine so feel free to experiment.

Food sources of resveratrol

Here are some of the riches food sources of resveratrol and how much they contain per 100 grams:

Dark chocolate: 0.022-0.430 mg
Red wine: 0.05-12.59 mg
Peanuts: 0.01-1.28 mg
Blueberries: 0.02-0.06 mg
Bilberries: 0.12-0.62 mg
Cranberries: 0.01-0.12 mg
Grapes: 0.05-1.68 mg
Pomegranate: 0.03-1.28 mg
Mulberries: 0.02-3.54 mg
Pistachios: 0.06-0.48 mg

As you can see, no foods contain a good amount of resveratrol. Red wine is the only food/beverage that could provide a dose of this compound that would impact the body in at least some minor way.

Even when it comes to red wines, most of them do not contain enough resveratrol to make any meaningful difference, and the possible benefits are outweighed by the health problems associated with ethanol.

Interactions

  • Apigenin
    Resveratrol can enhance the effects of apigenin.
  • Piperine
    Piperine from black pepper or other related types of pepper can increase the absorption of resveratrol by about 229% and the maximum serum resveratrol concentration by as much as 1544%. It does so by inhibiting glucuronidation, a process in the liver that signals to the body that it should secrete resveratrol.
  • Soy isoflavones
    Genistein, one of the main soy isoflavones, is highly synergistic with resveratrol for reducing adipose tissue.
  • Quercetin
    This combination is even more effective for preventing adipogenesis than the combination of resveratrol with Genistein. You can also combine all three supplements to achieve the highest effects.
  • Leucine
    SIRT1 and SIRT3 activity was increased synergistically in adipocytes and skeletal muscle in people who took this combination. Leucine can also prevent or lower the side effect of inhibiting muscle protein synthesis to at least some extent.
  • Turmeric
    Resveratrol and curcumin from turmeric were shown to reduce lung cancer in animal studies when taken together. This is likely because of their anti-inflammatory effects.
  • Grape Seed Extract
    Grape seed extract is significantly more potent in destroying cancer cells via the p53 pathway when taken with resveratrol.
  • Melatonin
    Resveratrol can increase both the beneficial and the unwanted effects of melatonin.

Where to buy Japanese knotweed?

In most countries, Amazon is the best option for ordering Japanese knotweed and other herbs and herbal supplements. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.

Some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.

FAQ

As with most other herbs and herbal supplements, it is best to cycle Japanese knotweed and take a break from it for about two days per week to reset your tolerance back to baseline. That will keep your body sensitive to the herb and allow you to keep getting the benefits in the long term.

When you take an extract standardized for resveratrol, you know exactly how potent it is and how much you need to take to get the desired outcome. Herbal extracts also tend to be cheaper than unextracted powders in many cases. However, many of the potentially beneficial compounds get lost during the extraction process. Therefore, if you know how potent the unextracted powder is, it is almost always a better option.

All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, you may need a highly accurate scale to dose them correctly (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes time which can add up over months or years. The disadvantage of capsules is that they are often made of bovine gelatine, which rarely comes from ethical sources.

Yes, you can. This herb should not impact your sleep in any negative way. Whether you take it in the morning or the evening typically doesn’t make much difference. Both options are fine so feel free to experiment. The most important thing to keep in mind is that resveratrol is fat-soluble so you should take it with food to absorb it well.

This herb should not become harmful once it exceeds the expiration date, but it can lose potency over time. Keep this herb or herbal supplement in a cold, dark, and dry place and it should remain just as potent for many months or even years.

Yes. The main problem with taking too much of this herb is that it may hinder the benefits of exercise.

While you could safely take higher doses, there is usually no point in taking more than 40 mg of resveratrol daily. This amount should give you most of the benefits without meaningful side effects. Paradoxically, taking a higher dose would likely lead to fewer benefits as the body would quickly become accustomed to the herb and you would experience more side effects related to the hindering of exercise performance.

The half-life of resveratrol in the body is anywhere from 1-3 hours. This compound should get metabolized and utilized within 12 hours of consuming it. The half-life of the other bioactive components in Japanese knotweed is mostly unknown. However, most of the effects of this herb are cumulative, so they mostly happen in the long term rather than acutely. Therefore, the half-life of this herb isn’t very relevant in practice.

The effects of this herb are cumulative. Therefore, you must take it for at least 2-4 weeks to notice most of the benefits. But again, cycling the herb and not taking it at least twice a week is necessary to prevent tolerance in the long term.

Yes, Japanese knotweed is vegan-friendly. If you buy this herb in a capsulated form, beware that the capsules often contain animal-based gelatin. Instead, find a brand that puts its products into cellulose capsules.

No, it does not. The herb does not interfere with fasting in any significant way. However, it is still much better to take Japanese knotweed with food as its main bioactive components are fat-soluble.

References

Most of the information in this guide is based on scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything you read in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.

We hope this guide has helped you determine if you should add Japanese knotweed to your supplement stack and how to do it right.

If you have any further questions or want to share your feedback, feel free to send us an email!

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