Pine Bark Extract

Overview

The active components in pine bark are similar to those of grapeseed extract, the procyanidin oligomers (PCOs), as well as phenolic acids (derivatives of benzoic and cinnamic acids). Virtually all the clinical work done on pine bark has been performed on the proprietary extract of the French Maritime pine, called PycnogenolTM. Pycnogenol has been found to be a potent antioxidant, and much of its pharmacologic activity comes from this activity, where it not only is able to enhance the synthesis of antioxidative enzymes, and the regeneration of vitamin C and E, but also act as a free-radical scavenger. Pycnogenol also exhibits antiinflammatory, and immunomodulatory activity, antagonizes vasoconstriction caused by epinephrine and norepinephrine by increasing the activity of nitric oxide synthase, improving cognitive function and cardioprotective effects, such as dilation of small blood vessels, a mild hypertensive effect (through the inhibition of angiotensin-converting enzyme) and the prevention of smoking-induced platelet aggregation (Rohdewald, 2002). Besides its clinical efficacy that has been found for improving diabetic retinopathy, recent animal studies have confirmed that pine bark (Pycnogenol) reduces oxidative stress in diabetic states (Maritim et al., 2003).

Comments

Pine bark extract is a good example of an herbal medicine that exerts so many pharmacologic activities, that it starts to sound like an unfounded panacea. However, the clinical work that is mounting on pine bark extract—notably in the form of Pycnogenol—is proving that it really is an effective herbal supplement.

Scientific Support

In a review of the many clinical studies on Pycnogenol (a standardized extract of French maritime pine bark), it has been found to be beneficial for many conditions with many pharmacological properties. The review included both peer-reviewed published clinical data, as well as results that had been presented in meetings, and foreign language studies not widely available. Pycnogenol has shown clinical efficacy in venous insufficiency, and retinal micro-hemorrhages, protection against UV-radiation-induced erythema, asthma, Lupus erythematosus (through immunomodulatory activity), cardiovascular disease, smoking-induced damage, and premenstural symptoms (PMS) (Rohdewald, 2002).

Attention-Deficit/Hyperactivity Disorder (ADHD)

Tenenbaum et al. (2002) performed a double-blind, placebo-controlled, crossover study of pycnogenol and methylphenidate for the treatment of ADHD. Neither Pycnogenol or methylphenidate outperformed placebo for the treatment of 24 adults with ADHD.

Asthma

Hosseini et al. (2001) conducted a randomized, double-blind, placebo-controlled, crossover study to ascertain if Pycnogenol was helpful in the treatment of asthma. The 26 participants were administered either 1 mg/ld/day (maximum 200 mg daily) of Pycnogenol or placebo for 4 weeks, and then crossed over to get the alternative treatment. Almost all the participants responded to Pycnogenol treatment compared to placebo, and no adverse effects were observed.

Erectile Dysfunction and Fertility

A clinical study was performed to investigate the effect of Pycnogenol and L-arginine in erectile dysfunction (ED). The 40 participants were supplemented with an L-arginine supplement (Sargenor, a solution of dipeptide arginyl aspartate providing 1.7 g L-arginine daily) for three months. Starting the second monthm, Pycnogenol (40 mg, two times daily) was added to the treatment. After one month of treatment with L-arginine ony 5% of the patients experienced normal erection, but in the second month, after pycnogenol was added to the therapy, that number went up to 80%. By the end of the third month of treatment, 92.5% of the participants experienced normal erection (Stanislavov and Nikolova, 2003).

Roseff (2002) conducted a nonrandomized, prospective, clinical study to determine the effects of Pycnogenol on sperm function parameters in subfertile men. The 19 particpants were given 200 mg Pycnogenol for 90 days, and their semen was analyzed before and after treatment for sperm count, motility scores, and morphology. After Pycnogenol treatment, sperm morphology increased by 38%, and the mannose receptor binding assay scores improved by 19%.

Diabetic Retinopathy

Pycnogenol was studied in several clinical studies for the treatment of diabetic retinopathy due to its known ability to increase capillary resistance, here is a review that was published on these clinical studies. Schonlau and Rohdewald (2001) conducted a systematic review of the literature on the treatment of diabetic retinopathy by Pycnogenol. They found 5 clinical studies with a total of 1289 patients that have been published since the late 1960’s. The authors noted that all but two of these studies were published in foreign languages, and that was the impetus for this review. They found all of the studies to clearly exhibit Pycnogenol’s ability to stop the progression of retinopathy, and to partly recover visual acuity. Additionally, they found tolerance to be very good and side effects rare (mostly gastrointestinal discomfort).

Blood Lipid and Antioxidant Capacity

In order to test the effect of Pycnogenol on oxidative stress and blood lipid levels, Devaraj et al. (2002) administered 150 mg/d Pycnogenol for 6 weeks to 25 healthy volunteers. A significant increase of the blood oxygen radical absorbance capacity (ORAC) was found, indicating beneficial antioxidant effects on oxidative stress. Pycnogenol treatment also significantly decreased LDL-cholesterol levels in the blood, and increased HDL-levels.

Silliman et al. (2003) conducted a nonrandomized clinical study to determine the effect of Pycnogenol on antioxidant capacity of serum and urine. The 27 participants were administered either Pycnogenol or placebo in a beverage. Blood samples were collected and analyzed for vitamin C and total antioxidant capactiy (ORAC), and urine samples were collected and analyzed for total phenolics, FRAP (ferric reducing antioxidant potential), and ORAC. There was no significant difference found in the vitamin C or antioxidant status of young healthy adults taking Pycnogenol.

Skin Health

Ni et al. (2002) performed a clinical examination to see if Pycnogenol had an effect on malasma (a common cutaneous hyperpigmentation disorder that primarily affects the sun-exposed areas on women). The study of Pycnogenol in this indication was performed because in earlier studies Pycnogenol had been reported to be an antioxidant several times more effective than vitamin C or E, and to protect against UV-induced radiation. The 30 women with melasma were administered 25 mg Pycnogenol with meals three times daily for 30 days. Pycnogenol was found to be 80% effective in reducing melasma with no adverse side effects observed. The authors noted that many of the participants reported the positive side-effects of pycnogenol treatment improving other symptoms/conditions, such as fatigue, constipation, anxiety, and pains in the body.

Gingival and Dental Health

Kimbrough et al. (2002) tested the effect of a chewing gum with and without Pycnogenol on gingival bleeding and plaque formation in a randomized, double-blind, placebo-controlled study. The 40 participants were instructed to chew gum with or without 5 mg Pycnogenol for the period of 14 days. The Pycnogenol chewing gum significantly reduced gingival bleeding and plaque accumulation.

Smoking-Induced Platelet Aggregation

Putter et al. (1999) tested the effect of Pycnogenol on cigarette smoking-induced platelet aggregation. Measures of increased heart rate and blood pressure due to cigarette smoking were not affected by either Pycnogenol or aspirin in a group of German smokers. However, after 500 mg aspirin or 125 mg Pycnogenol, the increased platelet aggregation induced by smoking in German subjects was prevented. The same study was performed on American smokers, and it took 200 mg to reduce platelet aggregation to significantly over 140 mg or 100 mg Pycnogenol. One advantage of Pycnogenol over aspirin (besides the lower dosage need to produce effect), was that Pycnogenol did not increase bleeding time; whereas, aspirin significantly increased it from 167 to 236 seconds.

Venous Insufficiency

Koch (2002) performed an open, controlled comparative study on Venostasin (horse chestnut seed extract) vs. Pycnogenol for the treatment of chronic venous insufficiency (CVI). The 40 participants with CVI were treated with either 600 mg Venostasin or 360 mg Pycnogenol daily for 4 weeks. In addition to assessments of CVI, blood lipid levels were monitored in the study. Pycnogenol was found to be more efficacious for CVI than Venostasin, and additionally improved blood lipid levels, whereas Venostasin did not.

Petrassi et al. (2000) conducted a clinical study with two phases (a randomized double-blind, placebo-controlled phase, and an open phase) to assess the efficacy of Pycnogenol for the treatment of CVI. Treatment of Pycnogenol in each phase was 100 mg, 2-3 times daily for 2 months. Of the 40 participants, 30 were treated with Pycnogenol; whereas 10 were treated with placebo. Pycnogenol was found to significantly reduce the clinical symptomology of CVI, with a lack of side effects or change in blood chemistry and hematologic parameters. The authors concluded it to be an safe and effective therapy for both CVI and related veno-capillary disturbances.

In a double-blind, placebo-controlled study, Pycnogenol was investigated for its efficacy for treating CVI. The 40 patients in the study were given either Pycnogenol (100 mg, three times daily) or placebo for 2 months. Pycnogenol was safely found to significantly reduce the symptomology of CVI compared to placebo (Arcangeli, 2000).

Systemic Lupus Erythematosus

In a pilot study on Pycnogenol for the treatment of systemic lupus erythematosus (SLE), 11 patients were administered Pycnogenol or placebo in addition to the regular treatment protochol. With Pycnogenol treatment a significant reduction of ROS production, apoptosis, p56(lck) activity and erythrocyte sedimentation rate was found. The authors concluded that Pycnogenol could be useful in the treatment of the inflammatory aspects of SLE (Stefanescu et al., 2001)

Safety / Dosage

The dosages of pine bark extract, in the form of Pycnogenol, that have been used in clinical studies ranges from approximately 75-360 mg daily, with 200 mg/daily being the most common dosage for oxidative stress and asthma, and 300 mg daily being most common for venous insufficiency. Dosages as low as 75 mg daily have shown good results on improving melasma in women.

Pycnogenol has been found to exhibit low acute and chronic toxicity, and mild side effects. Side effects were experienced in clinical studies in only a small percentage of participants (Rohdewald, 2002).

References

1.Arcangeli P. Pycnogenol in chronic venous insufficiency. Fitoterapia. 2000 Jun;71(3):236-44.

2.Devaraj S, Vega-Lopez S, Kaul N, Schonlau F, Rohdewald P, Jialal I. Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile. Lipids. 2002 Oct;37(10):931-4.

3.Hosseini S, Pishnamazi S, Sadrzadeh SM, Farid F, Farid R, Watson RR. Pycnogenol((R)) in the Management of Asthma. J Med Food. 2001 Winter;4(4):201-209.

4.Kimbrough C, Chun M, dela Roca G, Lau BH. PYCNOGENOL chewing gum minimizes gingival bleeding and plaque formation. Phytomedicine. 2002 Jul;9(5):410-3.

5.Koch R. Comparative study of Venostasin and Pycnogenol in chronic venous insufficiency. Phytother Res. 2002 Mar;16 Suppl 1:S1-5.

6.Maritim A, Dene BA, Sanders RA, Watkins JB 3rd. Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats. J Biochem Mol Toxicol. 2003;17(3):193-9.

7.Ni Z, Mu Y, Gulati O. Treatment of melasma with Pycnogenol. Phytother Res. 2002 Sep;16(6):567-71.

8.Petrassi C, Mastromarino A, Spartera C. PYCNOGENOL in chronic venous insufficiency. Phytomedicine. 2000 Oct;7(5):383-8.

9.Putter M, Grotemeyer KH, Wurthwein G, Araghi-Niknam M, Watson RR, Hosseini S, Rohdewald P. Inhibition of smoking-induced platelet aggregation by aspirin and pycnogenol. Thromb Res. 1999 Aug 15;95(4):155-61

10.Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68.

11.Roseff SJ. Improvement in sperm quality and function with French maritime pine tree bark extract. J Reprod Med. 2002 Oct;47(10):821-4.

12.Schonlau F, Rohdewald P. Pycnogenol for diabetic retinopathy. A review. Int Ophthalmol. 2001;24(3):161-71.

13.Silliman K, Parry J, Kirk LL, Prior RL. Pycnogenol does not impact the antioxidant or vitamin C status of healthy young adults. J Am Diet Assoc. 2003 Jan;103(1):67-72.

14.Stanislavov R, Nikolova V. Treatment of erectile dysfunction with pycnogenol and L-arginine. J Sex Marital Ther. 2003 May-Jun;29(3):207-13.

15.Stefanescu M, Matache C, Onu A, Tanaseanu S, Dragomir C, Constantinescu I, Schonlau F, Rohdewald P, Szegli G. Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients. Phytother Res. 2001 Dec;15(8):698-704.

16.Tenenbaum S, Paull JC, Sparrow EP, Dodd DK, Green L. An experimental comparison of Pycnogenol and methylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). J Atten Disord. 2002 Sep;6(2):49-60.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Fenugreek

Overview

Fenugreek is a popular spice in Indian cuisine and has a long use in both Ayervedic and Chinese traditional medicine, for uses including inducing lactation, inducing labor, aiding in digestion, and as a general health and wellness tonic (Basch et al., 2003; Gabay, 2002). Both animal and human clinical studies are finding that fenugreek shows promising therapeutic activity as a hypoglycemic and hypocholesterolaemic agent. The unique dietary fibers along with the high saponin content, and possibly an amino acid (4-Hydroxyisoleucine) in fenugreek is thought to be responsible for its activities (Madar, 2002; Sauvaire et al., 1998).

Comments

Vajifdar et al. (2000) included fenugreek dietary fiber in a dietary fiber mixture in a study which had favorable results on lowering LDL cholesterol, apolipoproteine A-1, body mass index and waist circumference. As the mechanisms of action of dietary fiber are assumed to be similar, this study shows promise for the use of fenugreek fiber for being helpful in ischemic heart disease. Likewise, fenugreek was found beneficial in the diabetic diet when combined with millet and legumes in another clinical study, and a combination of other herbs (Pathak et al., 2000; Bhardqaj et al., 1994).

Scientific Support

Type I & II Diabetes

Madar et al. (2002) tested the dietary effect of fenugreek in type II diabetics (non-insulin dependent) following the meal tolerance test (MTT). Powdered fenugreek (15 g) was added to the diets of type II diabetics, and found to significantly reduce the postprandial glucose levels, and non-significantly lower the plasma insulin levels as well. There was no effect on the blood lipid levels after 3 hours following the MTT.

Gupta et al. (2001) performed a double-blind, randomized, placebo-controlled study to determine the effect of fenugreek on glycemic control and insulin resistance in type II diabetics. The participants were given either fenugreek extract (hydroalcoholic; 1 g daily) or placebo for two months. Serum triglycerides were found to be reduced in the treatment group, as well as insulin control a a decrease in insulin resistance.

Sharma et al. (1990) tested the effect of fenugreek seeds on type I diabetic’s blood glucose levels and serum lipid profiles in a placebo-controlled clinical study. Fenugreek seed was administered in the treatment group diet (100 g daily), whereas isocaloric diets without fenugreek served as the control, and the diets were followed for 10 days. A 54% reduction in 24-hour urinary glucose excretion, along with significantly reduced serum total cholesterol, LDL, and VLDL cholesterol and triglycerides was found in the treatment group. The HDL levels remained unchanged between groups. The authors noted that fenugreek appeared useful in the diets of diabetics.

Hypocholesterolemic Effect

Sowmya and Rajyalakshmi (1999) tested the effect of dietary germinated fenugreek seed powder on blood lipid levels in hypocholesterolemic adults. Twenty participants were divided into two groups and asked to add the fenugreek powder to their meals for one month, the groups differed in the amount of fenugreek in the packet: either 12.5 g or 18 g daily. Both treatment levels resulted in a hypocholesterolemic effect, but the 18 g dosage resulted in significant reductions in total and LDL cholesterol levels. There were no changes found between the groups in HDL, VLDL and triglyceride levels. The authors claimed that the germination of the seeds was able to increase the solubility of the fiber content of fenugreek.

Safety / Dosage

Fenugreek seed powder has been found to be beneficial in the typical dosages of between 15-20 (and up) grams daily for reducing serum cholesterol levels and improving blood sugar control in diabetics. Fenugreek is considered quite safe, even at the higher doses needed for therapeutic use (Muralidhara et al., 1999). As is the case with other botanicals with high coumarin contents, there is concern with the potential adverse reaction of increasing bleeding, and an interaction with other blood-thinning drugs (Abebe, 2002).

References

1.Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002 Dec;27(6):391-401.

2.Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Med Rev. 2003 Feb;8(1):20-7.

3.Bhardwaj PK, Dasgupta DJ, Prashar BS, Kaushal SS. Control of hyperglycaemia and hyperlipidaemia by plant product. J Assoc Physicians India. 1994 Jan;42(1):33-5.

4.Gabay MP. Galactogogues: medications that induce lactation. J Hum Lact. 2002 Aug;18(3):274-9.

5.Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India. 2001 Nov;49:1057-61.

6.Hibasami H, Moteki H, Ishikawa K, Katsuzaki H, Imai K, Yoshioka K, Ishii Y, Komiya T. Protodioscin isolated from fenugreek (Trigonella foenumgraecum L.) induces cell death and morphological change indicative of apoptosis in leukemic cell line H-60, but not in gastric cancer cell line KATO III. Int J Mol Med. 2003 Jan;11(1):23-6.

7.Madar Z, Abel R, Samish S, Arad J. Glucose-lowering effect of fenugreek in non-insulin dependent diabetics. Eur J Clin Nutr. 1988 Jan;42(1):51-4.

8.Madar Z, Stark AH.New legume sources as therapeutic agents. Br J Nutr. 2002 Dec;88 Suppl 3:S287-92.

9.Muralidhara, Narasimhamurthy K, Viswanatha S, Ramesh BS. Acute and subchronic toxicity assessment of debitterized fenugreek powder in the mouse and rat. Food Chem Toxicol. 1999 Aug;37(8):831-8.

10.Pathak P, Srivastava S, Grover S. Development of food products based on millets, legumes and fenugreek seeds and their suitability in the diabetic diet. Int J Food Sci Nutr. 2000 Sep;51(5):409-14.

11.Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J, Gross R, Roye M, Leconte A, Gomis R, Ribes G. 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes. 1998 Feb;47(2):206-10.

12.Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr. 1990 Apr;44(4):301-6.

13.Sowmya P, Rajyalakshmi P. Hypocholesterolemic effect of germinated fenugreek seeds in human subjects. Plant Foods Hum Nutr. 1999;53(4):359-65.

14.Vajifdar BU, Goyal VS, Lokhandwala YY, Mhamunkar SR, Mahadik SP, Gawad AK, Halankar SA, Kulkarni HL. Is dietary fiber beneficial in chronic ischemic heart disease? J Assoc Physicians India. 2000 Sep;48(9):871-6.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS