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Grape Seed Extract (OPC)

Vitis vinifera
Evidence Level
Moderate
5 Clinical Trials
2 Documented Benefits
3/5 Evidence Score

Grape seed extract is a concentrated source of oligomeric proanthocyanidins (OPCs), a group of flavonoid polyphenols. Its best studied use is blood pressure. A pooled analysis of 16 randomized trials with 810 people found average drops of about 6 mmHg systolic and 3 mmHg diastolic, and the authors reported clearer effects in younger people, people with excess weight and people with metabolic syndrome. An earlier pooled analysis of 9 trials found a much smaller systolic drop and no significant change in diastolic pressure, and an 8-week trial in 70 adults found no significant effect, so the size of any benefit is uncertain. In a small trial in people with type 2 diabetes it raised glutathione and lowered CRP, but blood vessel function did not change. Grape seed extract is not a substitute for prescribed blood pressure medicine.

Studied Dose Trials pooled in one meta-analysis used 100 to 2000 mg/day. Recent blood pressure trials used 300 mg/day for 6 to 8 weeks, and one trial in type 2 diabetes used 600 mg/day for 4 weeks.
Active Compound Oligomeric proanthocyanidins (OPCs) built from catechin and epicatechin units. Commercial extracts are standardized for total polyphenols; MegaNatural-BP, a branded form used in several blood pressure trials, contains 90 to 93% total phenolics.

Benefits

Blood pressure reduction

A meta-analysis of 16 randomized trials (810 people) found grape seed extract lowered systolic pressure by about 6 mmHg and diastolic by about 3 mmHg, and systolic by about 8.5 mmHg in people with metabolic syndrome, though results varied widely between trials. An earlier meta-analysis of 9 trials found only a 1.5 mmHg systolic drop, and an 8-week trial in 70 adults found no significant change.

Supported by Trial 1, Trial 2

Antioxidant activity in blood markers

In a 4-week crossover trial in 32 people with type 2 diabetes at high cardiovascular risk, 600 mg/day raised whole blood glutathione, a key antioxidant, and lowered fructosamine and high-sensitivity CRP. Total antioxidant status, blood vessel function and insulin resistance did not change significantly.

Supported by Trial 5

Mechanism of action

1

Free radical scavenging

OPCs are polyphenols that neutralize free radicals in laboratory tests. In people, the clearest antioxidant signal so far is a rise in whole blood glutathione in one small trial, while total antioxidant status did not change.

2

Nitric oxide and blood vessel relaxation

Grape seed polyphenols are proposed to increase nitric oxide in blood vessel walls, which relaxes arteries. This is the main suggested explanation for the blood pressure findings, but it is not settled: blood vessel function did not improve in the type 2 diabetes trial or the 6-week prehypertension trial, and EFSA found no plausible mechanism established for one branded extract.

Clinical trials

1
Grape Seed Extract and Blood Pressure: Pooled Analysis of 16 Trials
PubMed

Meta-analysis of 16 randomized controlled trials from 12 articles. (Zhang et al. 2016, Medicine (Baltimore))

810 participants across 16 trials.

Systolic pressure fell by about 6.1 mmHg (95% CI -10.7 to -1.4) and diastolic by about 2.8 mmHg, with very high variation between trials (I2 94% for systolic). Drops were also significant in subgroups under 50 and with a BMI of 25 or more, and about 8.5 mmHg systolic in people with metabolic syndrome. The authors called for large, long-term trials. No heart outcomes were measured.

2
Grape Seed Extract and Cardiovascular Markers: Pooled Analysis of 9 Trials
PubMed

Meta-analysis of 9 randomized controlled trials. (Feringa et al. 2011, J Am Diet Assoc)

390 participants across 9 trials.

Systolic pressure fell by about 1.5 mmHg and heart rate by about 1.4 beats per minute. There was no significant effect on diastolic pressure, cholesterol, triglycerides or CRP.

3
Grape Seed Extract and Ambulatory Blood Pressure (8 Weeks)
PubMed

Randomized, double-blind, placebo-controlled parallel trial of 300 mg/day for 8 weeks; EFSA identified the extract as MegaNatural-BP. (Ras et al. 2013, Br J Nutr)

70 untreated adults with systolic pressure of 120 to 159 mmHg.

Versus placebo, systolic pressure changed by -3.0 mmHg and diastolic by -1.4 mmHg, neither statistically significant. ADMA, plasma renin activity and platelet aggregation were unaffected.

4
Grape Seed Extract Drink in Prehypertension (6 Weeks)
PubMed

Randomized, double-blind, placebo-controlled parallel trial of 300 mg/day grape seed extract in a juice drink for 6 weeks, followed by 4 weeks without it. (Park et al. 2016, Br J Nutr)

36 middle-aged adults with prehypertension randomized; 29 completed (12 in the extract group).

Systolic pressure fell 5.6% and diastolic 4.7% within the extract group. The systolic change differed significantly from placebo (P = 0.03); the diastolic difference did not (P = 0.08). Pressure returned to baseline after stopping. Flow-mediated dilation, lipids, glucose and oxidized LDL did not change.

5
Grape Seed Extract in Type 2 Diabetes at High Cardiovascular Risk (4 Weeks)
PubMed

Double-blind, randomized, placebo-controlled crossover trial of 600 mg/day for 4 weeks. (Kar et al. 2009, Diabet Med)

32 adults with type 2 diabetes (16 men, 16 women, mean age about 62) at high cardiovascular risk.

After grape seed extract but not placebo, fructosamine fell, whole blood glutathione rose, high-sensitivity CRP fell and total cholesterol decreased slightly (P = 0.05). Endothelial function, HOMA insulin resistance and total antioxidant status did not change significantly.

Side effects and drug interactions

Common Potential side effects

Generally well tolerated in the short trials listed here, which lasted 4 to 8 weeks; longer-term safety data are limited
Mild stomach upset is possible; taking it with food may help

Important Drug interactions

Blood thinners such as warfarin: grape seed polyphenols may affect platelet function; ask your doctor
Medicines processed by CYP3A4 (such as some statins and cyclosporine): an interaction is possible at high doses; check with a pharmacist
Iron supplements: polyphenols can reduce absorption of non-heme iron; take them about 2 hours apart
Blood pressure medicines: effects may add together; monitor your blood pressure

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Frequently asked questions about Grape Seed Extract (OPC)

How much grape seed extract should I take?

Recent blood pressure trials used 300 mg per day of an extract standardized for polyphenols, taken for 6 to 8 weeks; the trials pooled in one meta-analysis ranged from 100 to 2000 mg per day. Following the dose on the product label is the best guide.

What is grape seed extract used for?

Grape seed extract is best studied for blood pressure, where pooled randomized trials show a small average reduction, though results vary between studies. It is also taken as a general antioxidant. Skin and vein uses are popular but are not covered by the trials listed for this ingredient.

Does grape seed extract help with circulation or swelling?

Its OPCs are studied mainly for blood pressure and blood vessel function, and blood vessel function did not improve in the trials that measured it. Claims about leg swelling are not covered by the trials listed for this ingredient. Persistent leg swelling can have serious causes, so see a doctor about it rather than self-treating.

Does grape seed extract have side effects?

It was generally well tolerated in short trials; mild stomach upset is possible. Grape polyphenols may affect platelet function, so if you take anticoagulants or are scheduled for surgery, check with your doctor.

What is Grape Seed Extract?

Grape seed extract is a concentrated source of oligomeric proanthocyanidins (OPCs), a group of flavonoid polyphenols. Its best studied use is blood pressure. A pooled analysis of 16 randomized trials with 810 people found average drops of about 6 mmHg systolic and 3 mmHg diastolic, and the authors reported clearer effe…

Does Grape Seed Extract interact with any medications?

Possible interactions include: Blood thinners such as warfarin: grape seed polyphenols may affect platelet function; ask your doctor Medicines processed by CYP3A4 (such as some statins and cyclosporine): an interaction is possible at high doses; check with a pharmacist If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Grape Seed Extract?

NutraSmarts rates the evidence for Grape Seed Extract as Moderate (3 out of 5). It is backed by 5 study summaries and 6 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(6 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. J Am Diet Assoc. 2011;111(8):1173-81. doi: 10.1016/j.jada.2011.05.015.PubMedUsed to support: Meta-analysis of 9 randomized trials (390 people): grape seed extract lowered systolic blood pressure by about 1.5 mmHg and heart rate by about 1.4 beats per minute, with no significant effect on diastolic pressure, lipids or CRP.
  2. Zhang H, Liu S, Li L, Liu S, Liu S, Mi J, Tian G. The impact of grape seed extract treatment on blood pressure changes: A meta-analysis of 16 randomized controlled trials. Medicine (Baltimore). 2016;95(33):e4247. doi: 10.1097/MD.0000000000004247.PubMedUsed to support: Meta-analysis of 16 randomized trials (810 people): grape seed extract significantly lowered systolic (about -6.1 mmHg) and diastolic (about -2.8 mmHg) blood pressure, with very high variation between trials for systolic pressure (I2 94%). The systolic drop was about 8.5 mmHg in people with metabolic syndrome, and the authors concluded the effect was more obvious in younger or obese people. Trial doses ranged from 100 to 2000 mg/day. The authors called for large, long-term trials; no heart outcomes were measured.
  3. Park E, Edirisinghe I, Choy YY, Waterhouse A, Burton-Freeman B. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. Br J Nutr. 2016;115(2):226-38. doi: 10.1017/S0007114515004328.PubMedUsed to support: Randomized double-blind trial in adults with prehypertension (36 randomized, 29 completed): 300 mg/day grape seed extract in a juice drink for 6 weeks lowered systolic pressure 5.6% and diastolic 4.7% within the extract group; the systolic change differed from placebo (P = 0.03) and the diastolic change did not reach significance (P = 0.08). Pressure returned to baseline after stopping. Flow-mediated dilation, lipids, glucose and oxidized LDL were unchanged.
  4. Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet Med. 2009;26(5):526-31. doi: 10.1111/j.1464-5491.2009.02727.x.PubMedUsed to support: Double-blind randomized crossover trial in 32 people with type 2 diabetes at high cardiovascular risk: 600 mg/day grape seed extract for 4 weeks lowered fructosamine and high-sensitivity CRP and raised whole blood glutathione, with a small fall in total cholesterol. Endothelial function (measured by photoplethysmography), HOMA insulin resistance and total antioxidant status did not change significantly.
  5. Ras RT, Zock PL, Zebregs YE, Johnston NR, Webb DJ, Draijer R. Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br J Nutr. 2013;110(12):2234-41. doi: 10.1017/S000711451300161X.PubMedUsed to support: Randomized, double-blind, placebo-controlled trial in 70 untreated adults with pre- and stage I hypertension: 300 mg/day grape seed extract for 8 weeks did not significantly lower ambulatory blood pressure (systolic -3.0 mmHg, diastolic -1.4 mmHg versus placebo). ADMA, plasma renin activity and platelet aggregation were unaffected. EFSA identified the extract as MegaNatural-BP.
  6. EFSA Panel on Nutrition, Novel Foods and Food allergens (NDA). MegaNatural(®)-BP grape seed extract and maintenance of normal blood pressure: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J. 2021;19(8):e06776. doi: 10.2903/j.efsa.2021.6776.PubMedUsed to support: European Food Safety Authority opinion on MegaNatural-BP (90 to 93% total phenolics). Of two human trials it could use, a 6-week trial (300 mg/day) showed an effect on blood pressure and an 8-week trial at the same dose did not; two earlier small trials had reporting and statistical problems too severe to use. No plausible mechanism in humans was established, and EFSA concluded the evidence was insufficient for a claim on maintaining normal blood pressure.