Grape Seed Extract

 

• Shows senotherapeutic activity and increased mice lifespan by 9%. 

• Slowed down prostate cancer growth in a small human RCT. 

• Associated with decreased risk of hematologic malignancies (HR = 0.57 (95% CI = 0.37-0.88).

• In vitro and in vivo anticancer activity against colorectal cancer, prostate cancer, breast cancer, lung cancer, gastric cancer, squanomous carcinoma etc.

• Significant reductions in SBP (-6.077;  P = 0.011) and DBP (-2.803; P = 0.001) after grape seed extract treatment.

• Improved blood flow by reducing leg swelling, thins blood.  

• In one study with 15 people with NAFLD, -46% reduction in ALT after consuming GSE for 3 months (49).

The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice (2021)

Ageing-associated functional decline of organs and increased risk for age-related chronic pathologies is driven in part by the accumulation of senescent cells, which develop the senescence-associated secretory phenotype (SASP). Here we show that procyanidin C1 (PCC1), a polyphenolic component of grape seed extract (GSE), increases the healthspan and lifespan of mice through its action on senescent cells. By screening a library of natural products, we find that GSE, and PCC1 as one of its active components, have specific effects on senescent cells. At low concentrations, PCC1 appears to inhibit SASP formation, whereas it selectively kills senescent cells at higher concentrations, possibly by promoting production of reactive oxygen species and mitochondrial dysfunction. In rodent models, PCC1 depletes senescent cells in a treatment-damaged tumour microenvironment and enhances therapeutic efficacy when co-administered with chemotherapy. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival. We identify PCC1 as a natural senotherapeutic agent with in vivo activity and high potential for further development as a clinical intervention to delay, alleviate or prevent age-related pathologies.

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A chemical isolated from grape seed extract prolongs the lifespans of old mice by 9 per cent by clearing out their old, worn-out cells. The treatment also seems to make the mice physically fitter and reduces the size of tumours when used alongside chemotherapy to treat cancer.

The researchers identified a component of grape seed extract as a potentially effective senolytic, and they used it to extend the life span and healthspan of mice. A component of grape seed extract, known as procyanidin C1 (PCC1).

The researchers treated older mice with either PCC1 or a vehicle every 2 weeks for 4 months.

The team found a significant number of senescent cells in the kidneys, livers, lungs, and prostates of the aged mice. However, PCC1 treatment reversed this.

The PCC1-treated mice also had improved grip strength, maximum walking speed, hanging endurance, treadmill endurance, daily activity levels, and balance, compared with the mice who only received the vehicle.

In the third experiment, the researchers looked at very old mice to see what effect PCC1 may have on the longevity of the mice.

They found that mice treated with PCC1 lived, on average, 9.4% longer across their lifetime than mice who received the vehicle.

Louis N:

Folks you don’t need to take PCC1. If you read the actual paper, most of the experiments this group did were with plain old grape seed extract. The extract itself clearly has senomorphic and senolytic properties. And btw, Sierra Sciences has tested grape seed extract, and it also activates telomerase in their screens using human skin fibroblast cells.

Can grape seed extract slow prostate cancer spread? 2020

Between January and August 2018 – 27 patients were screened and 20 patients enrolled in the GSE trial. A planned pause in enrollment was carried out awaiting assessment of a futility analysis from initial results.

• Median (range) age and baseline PSA were 71 (60-83) and 2.65 (0.44-17.44)

• PSADT increased from 5.4 months to 6.4 months after treatment with GSE. (P<0.0001).

• 9 patients had a PSADT increase of 30% or greater.

• 8 patients were withdrawn early due to PSADT progression to <3 months.

• 11 adverse events were reported as possibly related to GSE. Hypertension (2) and dehydration (2) were reported most frequently.

The trial recruited 20 patients from UCHealth University of Colorado Hospital on the Anschutz Medical Campus and UCHealth Cancer Care and Hematology Clinic – Harmony Campus in Fort Collins. The subjects were men who had previously completed surgery, radiation treatment or both for their prostate cancer. They also had to have slowly increasing PSA (prostate specific antigen) numbers – a key marker for prostate cancer tumors – despite lacking evidence through imaging or other tests that the cancer had metastasized, or spread.

Slowing the next treatment step for prostate cancer

The idea was to see if taking 150 milligrams of grape seed extract twice a day for a year could slow the progression of the disease, as measured by the time it took for the patient’s PSA level to double, Maroni said. The longer that period, the longer providers could hold off on administering androgen deprivation therapy (ADT), which suppresses the hormones that drive prostate cancer.

ADT can blunt the cancer’s spread, but it also comes with a host of serious side effects, including hot flashes, fatigue, weight gain, weakened bones and increased risk for metabolic problems, heart disease and fractures, Maroni said.

Of course, some patients need that therapy to slow the spread of cancer to other parts of the body, he stressed.

“We don’t mind if a treatment gives patients side effects if there is a lot of value for them in terms of a longer life or a decreased burden of treatment later,” Maroni said. “But if the PSA is rising slowly, a patient may go for years before there are symptoms or detectable metastasis.”

In that case, the strategy is to watch and wait, and if grape seed extract lengthens that period, that’s a plus. The study suggests that the supplement treatment achieved at least partial success and deserves further study, Maroni said.

Using grape seed extract: posting the results

The American Association for Cancer Research accepted the findings of the study for a poster presentation, and Maroni summarized them in a recorded address at a June 22 virtual meeting of the organization. (View that poster presentation here.)

Anticancer and Cancer Chemopreventive Potential of Grape Seed Extract and Other Grape-Based Products, 2009

The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials (2016)

Twelve articles involving 16 clinical trials and 810 study subjects were analyzed. Overall analyses found significant reductions for SBP (WMD = -6.077; 95% CI: -10.736 to -1.419; P = 0.011) and DBP (WMD = -2.803; 95% CI: -4.417 to -1.189; P = 0.001) after grape seed extract treatment. In subgroup analyses, there were significant reductions in younger subjects (mean age < 50 years) for SBP (WMD = -6.049; 95% CI: -10.223 to -1.875; P = 0.005) and DBP (WMD = -3.116; 95% CI: -4.773 to -1.459; P < 0.001), in obese subjects (mean body mass index ≥ 25 kg/m) for SBP (WMD = -4.469; 95% CI: -6.628 to -2.310; P < 0.001), and in patients with metabolic syndrome for SBP (WMD = -8.487; 95% CI: -11.869 to -5.106; P < 0.001). Further meta-regression analyses showed that age, body mass index, and baseline blood pressure were negatively associated with the significant reductions of SBP and DBP after treatment. There was no indication of publication bias.

Grape Seed Extract (Examine)

• A small decrease in heart rate may occur following grape seed extract, although the studies are currently in persons with metabolic syndrome and not healthy persons

• An increase in blood flow appears to be reliable following ingestion of high dose procyanidins; this is likely the same increase seen with Pycnogenol due to the same molecules being bioactive

• May reduce levels of C-reactive protein

• A decrease in voluntary food intake has been noted with grape seed extract ingestion, appetite per se not measured

• A decrease in whole body oxidation appears to occur following ingestion of grape seed extract

• A reduction in leg swelling has been noted in sedentary women (sitting for a day or so), thought to be indicative of better blood flow with grape seed extract

Supplementation with grape seed may be associated with decreased risk of hematologic malignancies (21). 

Preclinical studies of grape seed proanthocyanidin extract (GSPE) suggest cardioprotective (4) (5) and anticancer effects (16) (17). Other studies suggest synergistic effects with doxorubicin (13) or that it can help minimize various drug-induced toxicities (3) (15) (22) (23). Topical application accelerated wound contraction and closure (8).

Preliminary studies in humans suggest grape seed extract can reduce LDL (6), increase total serum antioxidant activity (7), and benefit patients undergoing coronary artery bypass surgery (11). Meta-analyses suggest GSE may lower systolic blood pressure and heart rate, but are mixed on whether it improves lipid, glucose, and inflammatory markers (24) (25). 

1. Can reduce blood pressure

Several studies have researched the effects of GSE on high blood pressure.

A review of 16 studies in 810 people with high blood pressure or an elevated risk of it found that taking 100–2,000 mg of GSE daily significantly reduced systolic and diastolic blood pressure (the top and bottom number) by an average of 6.08 mmHg and 2.8 mmHg, respectively.

Those under the age of 50 with obesity or a metabolic disorder showed the greatest improvements.

The most promising results came from lower doses of 100–800 mg daily for 8–16 weeks, rather than a single dose of 800 mg or more (4).

Another study in 29 adults with high blood pressure found that taking 300 mg of GSE daily lowered systolic blood pressure by 5.6% and diastolic blood pressure by 4.7% after 6 weeks (5)

SUMMARY

GSE may help reduce blood pressure, particularly in young to middle-aged people and those who have excess weight.

2. Can improve blood flow

Some studies suggest that GSE may improve blood flow.

In an 8-week study in 17 healthy postmenopausal women, taking 400 mg of GSE had blood-thinning effects, potentially reducing the risk of blood clots (6).

An additional study in 8 healthy young women assessed the effects of a single 400-mg dose of proanthocyanidin from GSE immediately followed by 6 hours of sitting. It was shown to reduce leg swelling and edema by 70%, compared with not taking GSE.

In the same study, 8 other healthy young women who took a daily 133-mg dose of proanthocyanidins from GSE for 14 days experienced 40% less leg swelling after 6 hours of sitting (7).

SUMMARY

GSE has been shown to improve blood flow and reduce the risk of blood clotting, which may benefit those with circulatory problems.

3. Could reduce oxidative damage

An elevated blood level of LDL (bad) cholesterol is a known risk factor for heart disease.

The oxidation of LDL cholesterol significantly increases this risk and plays a central role in atherosclerosis, or the buildup of fatty plaque in your arteries (8).

GSE supplements have been found to reduce LDL oxidation triggered by high fat diets in several animal studies (9, 10, 11).

Some research in humans shows similar results (12, 13).

When 8 healthy people ate a high fat meal, taking 300 mg of GSE inhibited the oxidation of fats in the blood, compared with a 150% increase seen in those who did not take GSE (14).

In another study, 61 healthy adults saw a 13.9% reduction in oxidized LDL after taking 400 mg of GSE. However, a similar study was unable to replicate these results (5, 12).

Additionally, a study in 87 people undergoing heart surgery found that taking 400 mg of GSE the day before surgery significantly reduced oxidative stress. Therefore, GSE likely protected against further heart damage (15).

SUMMARY

GSE may help reduce your risk of heart disease by inhibiting the oxidation of LDL (bad) cholesterol and reducing oxidation to heart tissue during times of stress.

 

4. May improve collagen levels and bone strength

Increasing flavonoid consumption may improve collagen synthesis and bone formation.

As a rich source of flavonoids, GSE may thus help increase your bone density and strength.

In fact, animal studies have found that adding GSE to either a low calcium, standard, or high calcium diet can increase bone density, mineral content, and bone strength (16, 17).

Rheumatoid arthritis is an autoimmune condition that results in severe inflammation and the destruction of bone and joints.

Animal studies have shown that GSE may suppress bone destruction in inflammatory autoimmune arthritis (18, 19, 20).

GSE also significantly reduced pain, bony spurs, and joint damage in osteoarthritic mice, improving collagen levels and reducing cartilage loss (21).

Despite promising results from animal research, human studies are lacking.

SUMMARY

Animal studies show promising results regarding GSE’s ability to help treat arthritic conditions and promote collagen health. However, human-based research is lacking.

5. Supports your brain as it ages

Flavonoids’ combination of antioxidant and anti-inflammatory properties are thought to delay or reduce the onset of neurodegenerative diseases like Alzheimer’s disease (22).

One of the components of GSE is gallic acid, which animal and lab studies have shown can inhibit the formation of fibrils by beta-amyloid peptides (23).

Clusters of beta-amyloid proteins in the brain are characteristic of Alzheimer’s disease (23).

Animal studies have found that GSE may prevent memory loss, improve cognitive status and brain antioxidant levels, and reduce brain lesions and amyloid clusters (24, 25, 26, 27).

One 12-week study in 111 healthy older adults found that taking 150 mg of GSE daily improved attention, language, and both immediate and delayed memory (28).

However, human studies on the use of GSE in adults with preexisting memory or cognitive deficits are lacking.

SUMMARY

GSE shows potential to inhibit many of the degenerative characteristics of brain and cognitive decline. However, more human studies are needed.

6. Can improve kidney function

Your kidneys are particularly susceptible to oxidative damage, which is often irreversible.

Animal studies have shown that GSE may reduce kidney damage and improve function by reducing oxidative stress and inflammatory damage (29, 30, 31).

In one study, 23 people diagnosed with chronic renal failure were given 2 grams of GSE daily for 6 months and then compared with a placebo group. Urinary protein decreased by 3% and kidney filtration improved by 9%.

This means that the kidneys of those in the test group were much better able to filter urine than the kidneys of those in the placebo group (32).

SUMMARY

GSE may offer protection against damage from oxidative stress and inflammation, thus promoting kidney health.

7. Can inhibit infectious growth

GSE displays promising antibacterial and antifungal properties.

Studies have shown that GSE inhibits the growth of common foodborne bacteria, including Campylobacter and E. coli, both of which are often responsible for severe food poisoning and abdominal upset (33, 34).

In lab studies, GSE has been found to inhibit 43 strains of antibiotic-resistant Staphylococcus aureus bacteria (35).

Candida is a common yeast-like fungus that can sometimes result in candida overgrowth, or thrush. GSE is widely used in traditional medicine as a remedy for candida.

In one study, mice with vaginal candidiasis were given an intravaginal GSE solution every 2 days for 8 days. The infection was inhibited after 5 days and gone after 8 (36).

Unfortunately, human studies on GSE’s ability to help treat infections are still lacking.

SUMMARY

GSE may inhibit a variety of microbes and offer protection against antibiotic-resistant bacterial strains, foodborne bacterial illnesses, and fungal infections like candida.

8. May reduce cancer risk

The causes of cancer are complex, though DNA damage is a central characteristic.

A high intake of antioxidants, such as flavonoids and proanthocyanidins, are associated with a reduced risk of various cancers (37).

The antioxidant activity of GSE has shown potential to inhibit human breast, lung, gastric, oral squamous cell, liver, prostate, and pancreatic cell lines in lab settings (38, 39, 40, 41).

In animal studies, GSE has been shown to enhance the effect of different types of chemotherapy (42, 43, 44).

GSE appears to protect against oxidative stress and liver toxicity while targeting chemotherapy action on the cancerous cells (43, 44, 45).

A review of 41 animal studies found that either GSE or proanthocyanidins reduced cancer-induced toxicity and damage in all but one of the studies (44).

Keep in mind that the anticancer and chemopreventive potential of GSE and its proanthocyanidins may not be directly transferable to people with cancer. More studies in humans are needed.

SUMMARY

In lab studies, GSE has been shown to inhibit cancer in various human cell types. GSE also appears to reduce chemotherapy-induced toxicity in animal studies without negatively affecting treatment. More human-based research is needed.

9. May protect your liver

Your liver plays an important role in detoxifying harmful substances introduced to your body through drugs, viral infections, pollutants, alcohol, and more.

GSE appears to have a protective effect on your liver.

In test-tube studies, GSE reduced inflammation, recycled antioxidants, and protected against free radical damage during toxin exposure (46, 47, 48).

The liver enzyme alanine aminotransferase (ALT) is a key indicator of liver toxicity, meaning that its levels rise when the liver has sustained damage (37).

In one study, 15 people with non-alcoholic fatty liver disease and subsequent high ALT levels were given GSE for 3 months. Liver enzymes were monitored monthly, and results were compared with taking 2 grams of vitamin C per day.

After 3 months, the GSE group experienced a 46% reduction in ALT, while the vitamin C group showed little change (49).

SUMMARY

GSE appears to protect your liver against drug-induced toxicity and damage. However, more human studies are needed.

10. Enhances wound healing and appearance

Several animal studies have found GSE can aid wound healing (50, 51, 52).

Human studies show promise as well.

In one such study, 35 healthy adults who had undergone minor surgery were given either a 2% GSE cream or placebo. Those using the GSE cream experienced full wound healing after 8 days, while the placebo group took 14 days to heal.

These results are most likely due to high levels of proanthocyanidins in GSE triggering the release of growth factors in the skin (53).

In another 8-week study in 110 healthy young men, a 2% GSE cream improved skin appearance, elasticity, and sebum content, which can help reduce the signs of aging (54).

SUMMARY

GSE creams appear to increase growth factors in your skin. As such, they may aid wound healing and help reduce the signs of skin aging.

Possible side effects

GSE is generally considered safe with few side effects.

Dosages of around 300–800 mg per day for 8–16 weeks have been found to be safe and well tolerated in humans (4).

Those who are pregnant or breastfeeding should avoid it, as there is insufficient data on its effects in these populations.

GSE may lower blood pressure, thin your blood, and increase blood flow, so caution is advised for those taking blood-thinning or blood pressure medications (4, 6, 7).

Furthermore, it may reduce iron absorption, as well as improve liver function and drug metabolism. Consult your healthcare provider before taking GSE supplements (49, 55).

SUMMARY

GSE appears to be well tolerated. However, pregnant and breastfeeding women should avoid it. Also, those taking certain medications should discuss taking this supplement with their healthcare provider.

The bottom line

Grape seed extract (GSE) is a dietary supplement made from the seeds of grapes.

It’s a potent source of antioxidants, particularly proanthocyanidins.

The antioxidants in GSE may help alleviate the oxidative stress, inflammation, and tissue damage that can occur alongside chronic diseases.

By supplementing with GSE, you’ll reap the benefits of better heart, brain, kidney, liver, and skin health.