Many of you know that Pycnogenol has done quite well in a couple of studies on erectile dysfunction when combined with low dose arginine, something I cover in this link. However, Pycnogenol is a fairly expensive supplement and so one man in this thread posted the following question:
“Hey everyone — My question is if anyone has ever used Arginine with Grape Seed extract? I recently read that grape seed extract is pretty much the same thing as pycnogenol. (plus its a lot cheaper).”
“I bought 1000mg arginine and 250mg grape seed extract and I am planning on taking them twice per day to help boost my nitric oxide. I wanted to know if anyone has tried this? There’s a lot of information out there saying that taking regular l-arginine will get metabolized fast and we are all wasting our money.. However other information I read discusses about how arginine/grape seed or arginine/pycnogenol can boost nitric oxide and is great for erectile health.. so what gives? “
Well, that’s a great question. It seems like a great idea overall and the reason is that Grape Seed Extract a) comes from an actual food, something you cannot say for Pycnogenol (pine bark extract), and b) it has many great artery and endothelial-related properties that should make it excellent for improving erectile dysfunction. Here are just a few examples:
1. Nitric Oxide. A 2008 study sought to find out just how Grape Seed Extract relaxes arteries and the answer is simple: it does it the old fashioned, time proven way by favorably acting on eNOS (endothelial nitric oxide synthase), the same enzyme that Viagra acts upon.  This means that Grape Seed Extract will increase nitric oxide levels just like Pycnogenol. (For more information, see my page on Pycnogenol and Erectile Dysfunction.) Other studies have verifed the same thing. 
2. Lower Blood Pressure. Due to #1, it is no surprise that researchers found that it lowered blood pressure in patients with Metabolic Syndrome when given at a dosage of 150-300 mg/day.  The hallmark features of Metabolic Syndrome are elevated blood pressure, insulin resistance and triglycerides.
3. Blood Flow. If there’s one thing you need for good erections, it’s blood flow, eh? Well, one study on men and women with above average cardiovascular risk found that increased blood flow by taking “2 g/day of GSE (1 g of polyphenols).” 
4. Protection Against Arteriosclerosis. A 2010 study erified #1, i.e. that Grape Seed Extract increased nitric oxide and the authors noted that “has been shown to exhibit protective effects against cardiovascular events and atherosclerosis.”  Of course, protecting against arteriosclerosis should be one of the top goals for any male of any age. As the lining of our arteries calcify and thicken, they lose their ability to pump out nitric oxide, and this leads to heart disease and erectile dysfunction. How does it protect the lining of your arteries? An animal study noted that it 1) scavenged free radicals, 2) protected lipids from oxidatative damage and 3) inhibited the formation of the inflammatory cytokines (inflammatory messenger molecules).  All of these ground zero for the the arterial lesions that eventually lead to the buildup of plaque.
6. Glutathione. One very impressive result of the study in #4 is that Grape Seed Extract increased glutathione levels by 52%. This is very impressive as glutathione is the master detoxer of the body and this should definitely protect one’s long term health.
7. Venous Insufficiency. Grape Seed Extract seems to significantly help with venous insufficiency.  Venous insufficiecy is a disease of poor circulation and should be confused with Venous Leakage, which has a more direct effect on erectile function. Venous insufficiency plagues diabetics, for example, who cannot get proper circulation to their extremities allowing fluid and toxins to build up there.
SUPERCHARGE FOR ERECTILE STRENTH: This has not been proven in any study, but it is likely that adding low dose Arginine or Citrulline daily along with Grape Seed Extract will yield synergies. Citrulline has shown beneftis by itself to lower blood pressure and improve erectile dysfunction as I discuss in my page on The Benefits of Citrulline. Basically, Citrulline can supply a much needed base quantity of nitric oxide, which is important for middle aged men and then Grape Seed Extract can act on eNOS to make sure that that nitric oxide is preserved. Common dosages with Citrulline are 3 X 500 mg or 3 X 1 gram daily.
DOSAGE: Now, before I go on, I do have to say that one of the advantages of Pycnogenol is that they require solid standards with their extracts and seem to have good quality control. There will undoubtedly be more variability in any Grape Seed Extracts purchased. Furthermore, notice that the above studies use a wide range of dosages, 150 mg – 2 grams per day – in order to achieve the desired clinical effect.
LONG TERM SAFETY: It is true that Grape Seed Extract looks very promising to help men with erectile dysfunction, long term safety has not been established. As far as I know, all the studies have just looked at Grape Seed Extract for a few months and that is it.
CAUTIONS: Grape Seed Extact is known to be an aromatase inhibitor, which potentially could raise you testosterone a little . It also, in vitro at least, gives Vitamin C a longer shelf life. However, Grape Seed Extract has a couple of cautions that need to go along with it: 1) in combination with Vitamin C it apparently raises blood pressure  and 2) it may slightly decrease free testosterone because it can raise SHBG, the protein that binds to testosterone.
1) Clinical Science, 2008, 114:331 337, “Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract”
2) Metabolism, Dec 2009, 58(12):1743 1746, “Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome”
3) Cell & Molecular Biology, 34(10), “Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium”
4) Diabetic Medicine, May 2009, 26(5):526-531, “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”
5) Acta Pharacologica, Dec 2001, 22(12), “Anti-inflammatory effect and mechanism of proanthocyanidins from grape seed”
6) Nitric Oxide, Apr 2001, 5(2):137 149, “Protection of Primary Glial Cells by Grape Seed Proanthocyanidin Extract against Nitrosative/ Oxidative Stress”
7) Journal of Cardiovascular Pharmacology, Oct 2005, 46(4):445-451, “Grape Seed and Skin Extracts Inhibit Platelet Function and Release of Reactive Oxygen Intermediates”
8) Journal of Biomedicine and Biotechnology, 2004, 5:272-278, “Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects”
10) J Hypertensm 2005 Feb, 23(2):427-34, “The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial”
11) Cancer Res. 2006 Jun 1;66(11):5960-7