Does Grape Seed Extract Lower Cortisol? An Evidence-Based Analysis

November 24, 2025 •

5 min read

Animal studies have shown that chronic restraint stress significantly elevated serum corticosterone, the rodent equivalent of cortisol, which was subsequently reduced by oral administration of grape seed extract. This promising finding has sparked interest in whether grape seed extract can lower cortisol levels in humans, and the current state of the research requires a closer look.

Quick Summary

Limited but promising animal studies indicate grape seed extract may reduce elevated stress hormones, likely by protecting the adrenal glands from oxidative stress. Human evidence is still sparse, though some research points to indirect stress benefits through antioxidant effects.

Key Points

Animal Studies Show Reduction: In studies on rats exposed to chronic stress, oral grape seed extract was shown to reduce elevated levels of corticosterone, the rodent equivalent of cortisol.
Antioxidant Mechanism: The effect is primarily attributed to grape seed extract's potent antioxidant properties, which protect the adrenal glands from oxidative damage caused by stress.
Human Evidence is Limited: Human studies have not conclusively shown a direct cortisol-lowering effect from grape seed extract, although some research indicates potential benefits related to perceived stress and overall antioxidant status.
Complementary Stress Management: Grape seed extract should be viewed as a complementary tool, used alongside other natural strategies like adequate sleep, regular moderate exercise, and a healthy diet for holistic cortisol management.
Protects Adrenal Glands: Beyond lowering stress hormones, research suggests grape seed extract can protect and restore the cellular structure of the adrenal cortex after stress-induced damage.

Understanding Cortisol and Grape Seed Extract

Cortisol is a vital steroid hormone produced by the adrenal glands and is often called the 'stress hormone' because it plays a key role in the body's 'fight or flight' response. While a necessary part of a healthy stress response, chronically elevated cortisol levels can lead to various health problems, including weight gain, high blood pressure, and weakened immunity. Grape seed extract (GSE), conversely, is a dietary supplement derived from whole grape seeds and is a rich source of powerful antioxidants, particularly proanthocyanidins. These compounds are known for their ability to combat oxidative stress and inflammation, prompting research into their potential health benefits, including stress management.

Evidence from Animal Studies

Research conducted on animal models, particularly rats, offers some of the most direct evidence regarding grape seed extract's potential to influence stress hormones. One notable study focused on rats subjected to chronic physical stress.

Chronic Stress Elevation: The study found that chronic restraint stress significantly increased serum corticosterone (the main stress hormone in rodents) and markers of oxidative stress in the adrenal cortex.
GSE Intervention: Oral administration of grape seed extract to a stressed group of rats effectively reduced the elevated serum corticosterone levels and decreased the oxidative stress markers.
Adrenal Protection: The GSE-treated group also showed a significant improvement in the ultrastructure of the adrenal cortex, suggesting a protective effect on the stress-responsive organ.
Diabetes-Induced Injury: Another study on diabetic rats, a condition linked to high cortisol, found that GSE had a protective effect on the adrenal gland, helping to restore its normal structure.

These findings suggest a robust link between GSE's antioxidant properties and its ability to modulate the stress response and protect adrenal tissue in animal models. The underlying mechanism is likely GSE's capacity to reduce oxidative damage, which is a key byproduct of chronic stress.

The Limited Human Evidence

While animal studies show promise, the scientific evidence for grape seed extract directly lowering cortisol in humans is limited and inconclusive. Human research has primarily focused on indirect effects related to GSE's antioxidant and cardiovascular benefits.

Perceived Stress: A randomized, double-blind, placebo-controlled human study found that GSE positively modulated blood pressure and improved mood related to stress perception over 16 weeks. However, this study did not directly measure changes in cortisol levels.
Oxidative Stress Reduction: A study on individuals undergoing heart surgery found that taking GSE significantly reduced oxidative stress markers. While not a direct measure of cortisol, oxidative stress is closely linked to the body's stress response.
Metabolic Syndrome: Some studies have investigated GSE's effects on metabolic syndrome, a condition associated with high cortisol, but results are mixed, with one showing no change in insulin sensitivity.

Comparison of Grape Seed Extract Research: Animal vs. Human


Feature	Animal Studies (Primarily Rats)	Human Studies (Limited)
Direct Cortisol Measurement	Shows significant reduction in serum corticosterone (analogous to cortisol) under chronic stress.	Lacks direct measurement of cortisol reduction. Focuses more on related biomarkers.
Mechanism of Action	Strong evidence for antioxidant and anti-inflammatory mechanisms protecting the adrenal cortex from stress-induced oxidative damage.	Indirectly supports the antioxidant mechanism, with observed reductions in systemic oxidative stress.
Adrenal Gland Effects	Demonstrated protective and restorative effects on the adrenal gland's cellular structure following stress or injury.	No studies focused on direct effects on the adrenal gland. Findings based on perceived stress and biomarkers.
Observed Benefits	Reduction in stress hormone levels, decreased oxidative damage, improved adrenal structure.	Positive modulation of blood pressure and perceived stress, reductions in systemic oxidative stress markers.
Conclusion	Strong evidence of efficacy in mitigating physiological stress responses and elevated corticosterone.	Insufficient evidence to conclusively state that GSE lowers cortisol, though indirect benefits are noted.

How Grape Seed Extract Potentially Affects Cortisol

The primary pathway through which GSE may influence cortisol is by mitigating the negative effects of chronic stress on the body. Its rich concentration of proanthocyanidins provides potent antioxidant and anti-inflammatory protection.

Combating Oxidative Stress: When the body is under stress, it produces reactive oxygen species (free radicals), which can damage cells and contribute to inflammation. GSE's antioxidants neutralize these free radicals, thereby protecting cells and organs, including the adrenal glands responsible for cortisol production.
Supporting Adrenal Gland Health: By protecting the adrenal cortex from oxidative damage, GSE may help normalize the gland's function over time. This could prevent the overproduction of cortisol that occurs during prolonged stress exposure.
Indirect Stress Modulation: One human study found that GSE could improve perceived stress. This suggests that GSE might influence mood and mental well-being, which in turn can have a positive feedback effect on cortisol regulation.

Other Natural Strategies for Cortisol Reduction

For those looking to manage cortisol levels, a multi-faceted approach is most effective. GSE may be one tool in the arsenal, but it works best alongside other proven methods:

Prioritize Sleep: Chronic sleep deprivation is a known driver of high cortisol. Aim for 7-9 hours of quality sleep per night and maintain a consistent sleep schedule to help regulate your body's natural cortisol rhythm.
Incorporate Regular, Moderate Exercise: While intense exercise can temporarily spike cortisol, moderate, regular physical activity like walking, yoga, or swimming can help manage overall stress and lower cortisol over time.
Practice Mindfulness and Relaxation Techniques: Activities such as meditation, deep breathing exercises, and journaling can help activate the parasympathetic nervous system, promoting a state of calm and lowering cortisol.
Optimize Your Diet: Consuming a diet rich in whole foods, omega-3 fatty acids, and fiber can help regulate cortisol. Limiting added sugars, caffeine, and alcohol is also beneficial.
Consider Other Adaptogenic Supplements: Herbs like ashwagandha and omega-3 fatty acid supplements have also been shown to help regulate cortisol levels. Always consult a healthcare provider before starting any new supplement regimen.

Conclusion

While a direct cause-and-effect relationship in humans remains unproven, research on animal models provides strong evidence that grape seed extract can help lower elevated stress hormone levels and protect the adrenal glands from oxidative damage. The mechanism appears to be primarily driven by GSE's powerful antioxidant and anti-inflammatory effects. In humans, research is limited, though some studies suggest benefits related to perceived stress and overall antioxidant status. Therefore, while GSE is a promising supplement for supporting the body's response to stress, it should be considered a complementary part of a broader strategy for managing cortisol. Combining GSE with proven lifestyle modifications like improving sleep, managing stress, and eating a healthy diet offers the most comprehensive approach to naturally regulating cortisol levels.

For more information on the health benefits of grape seed extract, consult authoritative sources like Healthline: 10 Benefits of Grape Seed Extract, Based on Science.

Disclaimer: This information is for general knowledge and should not be taken as medical advice. Consult with a healthcare professional before starting any new supplement regimen.

Frequently Asked Questions

Grape seed extract contains powerful antioxidants called proanthocyanidins. These compounds help combat oxidative stress and inflammation, which are heightened during periods of chronic stress. By mitigating this damage, GSE may help support the adrenal glands and modulate the body's stress response.

No, the direct effect of grape seed extract on lowering cortisol levels has not been conclusively proven in humans. While promising animal studies exist, human trials are limited, with some showing effects on perceived stress and biomarkers rather than direct cortisol measurement.

Dosages used in studies have varied. However, there is no standardized dose specifically for stress or cortisol. It's best to consult a healthcare provider for personalized advice.

The timeframe for seeing effects can vary widely based on individual health, diet, and lifestyle. Animal studies have shown results over a period of weeks, but human studies are less clear on the timeline. Some benefits like reduced perceived stress might be noticed over a period of 4-16 weeks.

Some supplements like ashwagandha and omega-3 fatty acids are also associated with cortisol regulation. While they may complement each other, it is crucial to speak with a healthcare professional before combining supplements to ensure safety and avoid potential interactions.

Grape seed extract is generally considered safe for most people when taken as directed. Reported side effects are typically mild and may include headache, nausea, or dizziness. Individuals on blood-thinning or blood pressure medication should exercise caution and consult a doctor due to potential interactions.

The main takeaway is that while animal research strongly supports a cortisol-modulating effect, human evidence is still emerging and indirect. Grape seed extract's antioxidant properties are the key mechanism, and it is most effective as part of a holistic, healthy lifestyle for managing stress.