Grape seed extract

What it is

An extract made from the seeds of the grape vine, Vitis vinifera. It is rich in proanthocyanidins, polyphenols with antioxidant activity in the test tube. Products are sold alone or in combinations in concentrations of about 25 to 500 mg.

What the research says

Meta-analyses of small trials find a small drop in blood pressure and heart rate, but they disagree on which blood pressure number moves: a 2011 analysis of nine trials found systolic pressure fell about 1.5 mmHg with no effect on diastolic, while a 2022 analysis of nineteen trials found diastolic fell about 2.2 mmHg with no significant effect on systolic, and heterogeneity was very high. It did not lower cholesterol or CRP. A randomised trial in breast cancer survivors found no benefit for radiation-induced breast hardening. It appears well tolerated in trials, with no liver injury reported.

Evidence grade: Limited evidence.

What goes wrong

A published case report describes recurrent nausea, vomiting, diarrhoea and weakness in a man taking grape seed extract that resolved when he stopped it. (Source 1)

• Case report, Very low certainty.
• Size: 1 patient.
• Who: 49-year-old man.
• How long: 5-year follow-up after stopping.
• Result: symptoms resolved after discontinuation; symptom-free 5 years later.
• Funding: not stated.

We report a 49-year-old male who presented with recurrent nausea, vomiting, diarrhea, and acute weakness following GSE use.

LiverTox reports mild side effects in trials (itchy skin, dizziness, headache, nausea) at rates often similar to placebo, and no published cases of liver injury. (Source 2)

• Official position, Low certainty.
• Size: not applicable.
• Who: clinical trial participants.
• How long: largely short-term trials.
• Result: no quantified rate given; likelihood score E (unlikely cause of liver injury)
• Funding: government (NIDDK)

Adverse events reported in clinical trials have included mild degrees of itchy skin, dizziness, headache, and nausea but a similar incidence of these adverse events was often found in patients receiving placebos.

NCCAM (now NCCIH) stated in 2012 that interactions between grape seed extract and medicines or other supplements have not been carefully studied. (Source 3)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: not applicable.
• How long: not applicable.
• Result: no data.
• Funding: government (NIH)

Interactions between grape seed extract and medicines or other supplements have not been carefully studied.

What the evidence supports

A 2011 meta-analysis of nine small RCTs found grape seed extract significantly lowered systolic blood pressure (by about 1.5 mmHg) and heart rate (by about 1.4 beats per minute). (Source 4)

• Meta-analysis, Low certainty.
• Size: 390 participants across 9 RCTs.
• Who: adults in randomised trials.
• How long: varied (not stated in abstract)
• Result: SBP WMD -1.54 mmHg (95% CI -2.85 to -0.22, P=0.02); HR WMD -1.42 bpm (95% CI -2.50 to -0.34, P=0.01); no significant effect on DBP, lipids or CRP.
• Funding: not stated.

grape seed extract significantly lowered systolic blood pressure (weighted mean difference -1.54 mm Hg (95% confidence interval -2.85 to -0.22, P=0.02])

A 2022 meta-analysis of nineteen trials found grape seed extract significantly reduced diastolic blood pressure (by about 2.2 mmHg) and heart rate, with very high between-study heterogeneity (I2 88.8% for diastolic pressure). (Source 5)

• Meta-analysis, Low certainty.
• Size: 19 controlled trials (participant total not in abstract)
• Who: adults.
• How long: long-term (varied)
• Result: DBP WMD -2.20 mmHg (95% CI -3.79 to -0.60, I2 88.8%); HR WMD -1.25 bpm; SBP WMD -3.55 mmHg (95% CI -7.59 to 0.49, I2 97.4%, not significant); FMD not significant.
• Funding: not stated.

GSE supplementation significantly reduced DBP (WMD: −2.20 mmHg, 95% CI: −3.79 to −0.60, I² = 88.8%)

What the evidence does not support

The same meta-analysis found no effect on diastolic blood pressure, cholesterol or CRP. (Source 4)

• Meta-analysis, Low certainty.
• Size: 390 participants across 9 RCTs.
• Who: adults in randomised trials.
• How long: varied.
• Result: no significant effect.
• Funding: not stated.

No significant effect on diastolic blood pressure, lipid levels, or CRP was found.

In the 2022 meta-analysis, grape seed extract had no significant effect on systolic blood pressure or endothelial function (FMD). (Source 5)

• Meta-analysis, Low certainty.
• Size: 19 controlled trials.
• Who: adults.
• How long: long-term (varied)
• Result: FMD WMD 1.02% (95% CI -0.62 to 2.66); SBP WMD -3.55 mmHg (95% CI -7.59 to 0.49)
• Funding: not stated.

but had no significant effects on FMD (WMD: 1.02%, 95% CI: −0.62 to 2.66, I² = 92.0%) and SBP

A randomised placebo-controlled phase II trial found grape seed proanthocyanidin extract did not reduce breast hardening after radiotherapy. (Source 6)

• Randomized trial, Low certainty.
• Size: 66 women (44 GSPE, 22 placebo)
• Who: women with moderate or marked breast induration a mean 10.8 years after radiotherapy for early breast cancer.
• How long: 6 months of treatment, assessed at 12 months.
• Result: ≥50% reduction in induration area in 29.5% GSPE vs 27% placebo (NS)
• Funding: not stated in abstract.

The study failed to show efficacy of orally-adminstered GSPE in patients with breast induration following radiotherapy for breast cancer.

Where the evidence is mixed

A 30-day RCT in people with type 2 diabetes reported lower systolic pressure and fasting glucose with grape seed extract, but no change in cholesterol, triglycerides or diastolic pressure. (Source 7)

• Randomized trial, Low certainty.
• Size: 74 patients (38 GSE, 36 placebo)
• Who: adults with type 2 diabetes in Iran.
• How long: 30 days.
• Result: SBP 121.94 vs 125.83 (P=0.002); FBS 129.87 vs 144.75 (P=0.001); no significant change in lipids or DBP.
• Funding: independent (university grant)

There were no significant changes in total cholesterol, HDL, LDL, TG, and DBP between the two groups.

A review of supplements and surgical bleeding found no reports of coagulation or platelet adverse effects for grape seed extract. (Source 8)

• Systematic review, Very low certainty.
• Size: not applicable.
• Who: surgical patients (narrative review)
• How long: not applicable.
• Result: no reports found.
• Funding: not stated.

There is no report on adverse effects related to coagulation and platelet function for these herbs.

Where the research disagrees

Which blood pressure number grape seed extract lowers

• Feringa et al. 2011 (9 RCTs), meta-analysis: grape seed extract appears to significantly lower systolic blood pressure and heart rate, with no effect on lipid or CRP levels (Source 4)
• Foshati et al. 2022 (19 trials), meta-analysis: but had no significant effects on FMD (WMD: 1.02%, 95% CI: −0.62 to 2.66, I² = 92.0%) and SBP (Source 5)

How much

• Reference intake: No RDA or AI exists; grape seed extract is not an essential nutrient and, per LiverTox (2023), has not been approved for any medical condition by the FDA. (Source 2)
• Upper limit: No tolerable upper intake level has been set by any body in the sources we reached. NCCAM (2012) said it has been used safely for up to 8 weeks in clinical trials. (Source 3)
• Studied: 100 mg three times a day for 6 months (Brooker 2006, breast induration trial). (Source 6)
• Studied: 263.2 mg (standardised to 250 mg proanthocyanidin) twice daily for 30 days (Zaeemzadeh 2024). (Source 7)

A common belief, and what the research shows

The belief: Grape seed extract is a proven treatment for heart and circulation conditions.

What the research shows: LiverTox states: "None of these claims, however, has been verified in properly designed and adequately powered prospective studies". Meta-analyses show only small blood pressure changes, and they disagree on which reading moves.

Questions and answers

What is it?

Grape seed extract is made from the seeds of grapes (Vitis vinifera). It is rich in proanthocyanidins, plant polyphenols that act as antioxidants in the test tube. (Source 2)

What does it do in the body?

In pooled trials it lowered blood pressure and heart rate by small amounts (around 1 to 2 mmHg and 1 to 1.5 beats per minute). It did not change cholesterol or CRP. The reviews disagree on whether it is the top or bottom blood pressure number that moves. (Source 4)

Is it good or bad for you?

In trials it appears well tolerated, with mild side effects at rates similar to placebo and no reported liver injury. Benefits are small and uncertain, and the evidence has not confirmed the many health claims made for it. (Source 2)

How do you get more of it?

It is taken as a capsule or tablet extract. Products range from about 25 to 500 mg, alone or mixed with other ingredients. (Source 2)

If it is harmful, what reduces it?

Does not apply. It is not something the body makes or needs to clear. In one case report, symptoms went away once the person stopped taking it. (Source 1)

Why might someone be low in it or missing it?

Does not apply. Grape seed extract is not an essential nutrient, so there is no deficiency state to be low in. (Source 2)

We searched: LiverTox, NCCAM 2012 fact sheet, two meta-analyses; none describe a deficiency state.

Which whole foods contain it or feed it?

The seeds come from grapes. Grapes are widely eaten as fruit, juice and wine. The sources we reached did not measure how much proanthocyanidin whole grapes supply. (Source 2)

What happens if you do not have it?

Nothing is known to happen. It is not an essential nutrient, and no deficiency effects are described. (Source 2)

We searched: LiverTox, NCCAM 2012, Feringa 2011 and Foshati 2022 meta-analyses.

How can you test for it?

We found no clinical test for grape seed extract or proanthocyanidin status in the literature we searched. (Source 4)

We searched: LiverTox; meta-analyses of RCTs; searches for grape seed extract trials and adverse events.

References

1. Journal of Dietary Supplements. Adverse Effects of Grape Seed Extract Supplement: A Clinical Case and Long-Term Follow-Up. 2015. PMID 25688637, DOI 10.3109/19390211.2015.1008617. Read the source
2. NIDDK / NCBI Bookshelf. Grape Seed - LiverTox (last update March 20, 2023). 2023. Read the source
3. NIH National Center for Complementary and Alternative Medicine (now NCCIH), via govinfo.gov. Grape Seed Extract (Herbs at a Glance), updated April 2012. 2012. Read the source
4. Journal of the American Dietetic Association (abstract via NCBI Bookshelf DARE record). The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. 2011. PMID 21802563. Read the source
5. Pharmacological Research. The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis. 2022. DOI 10.1016/j.phrs.2021.105905. Read the source
6. Radiotherapy and Oncology. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration. 2006. PMID 16546280. Read the source
7. Jundishapur Journal of Natural Pharmaceutical Products. A 4-week Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Use of Grape Seed Extract for Reducing Plasma Glucose, Lipid Profile, and Blood Pressure in Patients with Type 2 Diabetes Mellitus. 2024. DOI 10.5812/jjnpp-146854. Read the source
8. Medicines (MDPI). Commonly Used Dietary Supplements on Coagulation Function during Surgery. 2015. DOI 10.3390/medicines2030157. Read the source