Oligomeric proanthocyanidins' therapeutic uses

• PRINCIPAL PROPOSED USES: Easy bruising, edema following injury or surgery, travelers’ thrombosis, varicose veins, weight loss
• OTHER PROPOSED USES: Aging skin, allergies, asthma, atherosclerosis prevention, attention deficit disorder, cancer prevention, diabetes (blood sugar control), diabetic neuropathy and retinopathy, hemorrhoids, hypertension, impaired night vision, impotence, liver cirrhosis, lupus, menopause, periodontal disease, premenstrual syndrome

DEFINITION: Natural plant product used to treat specific health conditions.

Overview

One of the best-selling herbal products of the early 1990s was an extract of the bark of French maritime pine. This substance consists of a family of chemicals known scientifically as oligomeric proanthocyanidin complexes (OPCs) or procyanidolic oligomers (PCOs). Similar substances are also found in grape seeds. The research record is complicated by the fact that certain identically named proprietary products have consisted at different times of various proportions of these related substances. OPCs are marketed for a wide variety of uses. However, there is no solid evidence that they are effective for any medical condition.

Requirements and Sources

OPCs are not a single chemical but a group of closely related compounds. Several food sources contain similar chemicals: red wine, cranberries, blueberries, bilberries, black and green tea, black currant, onions, legumes, parsley, and the herb hawthorn. However, most OPC supplements are made from either grape seed or the bark of the maritime pine. These two OPC sources lead to products that are not necessarily identical in function, although there are many similarities. In the discussion of scientific studies below, the source of the OPCs used is indicated wherever possible. In some cases, identifying the exact product is difficult, as both grape seed and pine bark OPCs, or their combination, have been sold under the same name at various times.

Therapeutic Dosages

Studies have used doses between 50 and 300 milligrams (mg) daily to treat specific medical conditions. For use as a general antioxidant, 50 mg of OPCs daily is often recommended. However, there is no conclusive evidence that this dose provides any health benefits.

Taking two 50 mg tablets each day may strengthen capillaries. With 150 mg per day, symptoms of chronic venous insufficiency may be alleviated, and patients with chronic obstructive pulmonary disease (COPD) may experience better lung function. To treat menopause-related hot flashes and insomnia, 200 mg per day is recommended. Though these dosages have been used successfully in trials for specific groups of individuals, they are not scientifically proven treatments for any illness.

Therapeutic Uses

The best-documented use of OPCs is to treat chronic venous insufficiency, a condition closely related to varicose veins. In these conditions, blood pools in the legs, causing aching, pain, heaviness, swelling, fatigue, and unsightly visible veins. Preliminary evidence suggests that OPCs from pine bark or grape seed can relieve leg pain and swelling caused by chronic venous insufficiency. However, no studies have evaluated whether regular use of OPCs can make visible varicose veins disappear or prevent new ones from developing. Other small, double-blind trials suggest that OPCs may help reduce swelling caused by injuries or surgery.

Evidence from one small, double-blind trial suggests that OPCs from bilberry and grape seeds may reduce the general fluid retention and swelling that can occur in premenstrual syndrome (PMS). One large study found some evidence that the use of OPCs from pine bark might help prevent the leg blood clots that can develop on a long airplane flight.

Some studies suggest OPCs from pine bark, alone or with arginine, may be helpful for erectile dysfunction. For example, in a double-blind, placebo-controlled trial, 124 men aged thirty to fifty years old with moderate erectile dysfunction were randomized to take Preloxa formulation of pine bark extract and arginineor a placebo for six months. The men who took Prelox experienced an improvement in their condition over those who took a placebo. Though most trials have been small, OPCs show promise for treating erectile dysfunction in some men, particularly when combined with L-arginine.

In a double-blind, placebo-controlled study of sixty-one children with attention deficit hyperactivity disorder (ADHD), the use of OPCs from pine bark at a dose of one gram per kilogram of body weight per day appeared to improve some measurements of disease severity. Some studies indicate that the brain’s alpha, beta, and theta waves are positively affected by OPCs, strengthening the blood-brain barrier and allowing improved neurotransmitter activity, cognitive function, and blood flow.

Two small, double-blind pilot studies suggest that OPCs from pine bark might help reduce asthma symptoms. OPCs are also often recommended for allergies, but an eight-week double-blind trial of forty-nine individuals found no benefit with grape seed extract. On a slightly more positive note, a preliminary trial involving thirty-nine people with seasonal allergies found that those who took OPCs at least five weeks before the start of the season experienced more symptom relief than the control group. And those that took OPCs for an extended periodfor example, seven to eight weeks before the seasonseemed to have better results.

OPCs might marginally improve blood sugar control in people with diabetes, according to a double-blind study of seventy-seven people with type 2 diabetes. Some evidence suggests that OPCs protect and strengthen collagen and elastin. Theoretically, this could mean that OPCs are helpful for aging skin, and they are widely sold for this purpose, but there is no direct evidence that the herbs work.

Hemorrhoids are varicose veins in and around the anus. Since OPCs are used to treat varicose veins, it is thought that this substance would also be helpful for people who have hemorrhoids. A randomized trial involving eighty-four people with hemorrhoids found that both the oral and topical forms of Pycnogenol (pine bark extract) eased symptoms, including bleeding.

One study suggests that while OPCs alone may not reduce cholesterol levels, some benefits may occur when they are combined with chromium. OPCs are strong antioxidants. Vitamin E defends against fat-soluble oxidants, and vitamin C neutralizes water-soluble ones, but OPCs are active against both types. Based on the unproven belief that antioxidants offer many health benefits, regular use of OPCs has been proposed as a measure to prevent cancer, diabetic neuropathy, diabetic retinopathy, and heart disease.

OPCs have been tried as a treatment for impaired night vision, lupussystemic lupus erythematosuseasy bruising, high blood pressure, and liver cirrhosis. However, more research must be performed to discover whether it provides any benefits in these conditions. A double-blind, placebo-controlled study of questionable validity reported that the use of OPCs from pine bark produced benefits in all symptoms of menopause.

One study failed to find OPCs significantly helpful for weight loss. Another failed to find OPCs helpful for reducing the side effects of radiation therapy for breast cancer.

Scientific Evidence

Venous insufficiency (varicose veins). Some preliminary evidence for the use of OPCs to treat people with symptoms of venous insufficiency has shown promise. A double-blind, placebo-controlled study of seventy-one subjects found that grape seed OPCs, taken at a dose of 100 mg three times daily, significantly improved major symptoms, including heaviness, swelling, and leg discomfort. Over one month, 75 percent of the participants treated with OPCs improved substantially. This result is less impressive considering that significant improvement was also seen in 41 percent of the placebo group; nonetheless, OPCs still did significantly better than the placebo.

A two-month double-blind, placebo-controlled trial of forty people with chronic venous insufficiency found that 100 mg of pine bark OPCs three times daily significantly reduced edema, pain, and the sensation of leg heaviness. A similar study of twenty individuals also found OPCs from pine bark effective.

A placebo-controlled study (blinding not stated) that enrolled 364 people with varicose veins found that treatment with grape seed OPCs produced statistically significant improvements compared with baseline. There was a lesser response in the placebo group, but whether this difference was statistically significant was not stated.

OPCs have also been compared against other natural treatments for venous insufficiency. A double-blind study of fifty people with varicose veins of the legs found that doses of 150 mg per day of grape seed OPCs were more effective in reducing symptoms and signs than the bioflavonoid diosmin. Similarly, a double-blind study of thirty-nine people found pine bark OPCs more effective than the herb horse chestnut.

Edema after surgery or injury. Breast cancer surgery often leads to swelling of the arm. A double-blind, placebo-controlled study of sixty-three postoperative breast cancer patients found that 600 mg of grape seed OPCs daily for six months reduced edema, pain, and peculiar sensations known as paresthesias. Also, in a double-blind, placebo-controlled study of thirty-two people who had received facial surgery, edema disappeared much faster in the group treated with grape seed OPCs.

Another ten-day, double-blind, placebo-controlled study enrolling fifty participants found that grape seed OPCs improved the rate at which edema disappeared following sports injuries.

Blood clots after plane flights. It is commonly thought, though not proven, that the immobility endured during a long plane flight can lead to the development of potentially dangerous blood clots in the legs, known as deep venous thrombosis (DVTs). Travelers at high risk are often recommended to take aspirin to thin their blood prior to flying.

One crossover study of twenty-two individuals who smoked cigarettes found that 100 mg of OPCs had a blood-thinning effect equivalent to 500 mg of aspirin. Based on this, a large double-blind study was performed to evaluate whether OPCs from pine bark could help reduce the risk of blood clots on long airplane flights. The study followed 198 people at high risk for blood clots. Some participants received 200 mg of OPCs two to three hours before the flight, 200 mg six hours later, and 100 mg the next dayothers received a placebo on the same schedule. The average flight length was about eight hours. The results indicated that using OPCs significantly reduced the risk of blood clots. There were five cases of DVTs or superficial thrombosis in the placebo group, compared with none in the OPC group, a statistically significant difference.

Another substantial double-blind study including 204 participants found benefit with a product that contains OPCs combined with nattokinase. Nattokinase, also known as natto, is an extract of fermented soy thought to have some blood-clot-dissolving properties.

Periodontal disease. Inflammation of the gumsgingivitisand plaque formation lead to periodontal disease, one of the most common causes of tooth loss. A fourteen-day double-blind, placebo-controlled trial of forty people evaluated the potential benefits of a chewing gum product containing five mg of OPCs from pine bark. Use of the OPC gum resulted in significant improvements in gum health and reductions in plaque formation; no similar benefits were seen in the placebo group.

Atherosclerosis. Although there are no reliable human studies, animal evidence suggests that OPCs can slow or reverse atherosclerosis. This suggests (but does not prove) that OPCs might be helpful for preventing heart disease.

Safety Issues

OPCs have been extensively tested for safety and are generally considered nonmutagenic and nontoxic, even at high levels. Side effects are rare, and when they occur, they are limited to occasional allergic reactions and mild digestive distress.

However, one study found that combining OPCs and vitamin C might slightly increase blood pressure in people with high blood pressure. Neither treatment alone had this effect. These results may have been a statistical fluke, but nonetheless, people with hypertension should use the combination of vitamin C and OPCs only with caution. One study, though, found that Pycnogenolpine bark extractmay help improve kidney function in people with metabolic syndrome who take high blood pressure medicine. Maximum safe dosages for young children, pregnant or nursing women, and those with severe liver or kidney disease have not been established.

Important Interactions

OPCs may have some anticoagulant properties when taken in high doses, so individuals on blood-thinner drugs, such as warfarin (Coumadin), heparin, clopidogrel (Plavix), ticlopidine (Ticlid), pentoxifylline (Trental), or aspirin should use them only under medical supervision.

Bibliography

Belcaro, G., et al. “Pycnogenol Treatment of Acute Hemorrhoidal Episodes.” Phytotherapy Research, vol. 24, no. 3, 2010, pp. 438-44.

Kar, P., et al. “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.” Diabetic Medicine, vol. 26, no. 5, 2009, pp. 526-31.

Ledda, A., et al. “Investigation of a Complex Plant Extract for Mild to Moderate Erectile Dysfunction in a Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study. BJU International, vol. 106, no. 7, 2010, pp. 1030-33.

Nie, Fanxuan, et al. “Oligomeric Proanthocyanidins: An Updated Review of Their Natural Sources, Synthesis, and Potentials.” Antioxidants, vol. 12, no. 5, 26 Apr. 2023, p. 1004. doi:10.3390/antiox12051004.

Rauf, Abdur, et al. "Proanthocyanidins: A Comprehensive Review." Biomedicine & Pharmacotherapy, vol. 116, Aug. 2019, p. 108999. doi:10.1016/j.biopha.2019.108999.

Wang, Tsz Ki, et al. “Proanthocyanidins Should Be a Candidate in the Treatment of Cancer, Cardiovascular Diseases and Lipid Metabolic Disorder.” Molecules (Basel, Switzerland), vol. 25, no. 24, Dec. 2020, p. 5971. doi:10.3390/molecules25245971.

Wilson, D., et al. “A Randomized, Double-Blind, Placebo-Controlled Exploratory Study to Evaluate the Potential of Pycnogenol for Improving Allergic Rhinitis Symptoms.” Phytotherapy Research, vol. 24, no. 8, 2010, pp. 1115-19.