French maritime pine bark extract has been used as a supplement in several clinical and non-clinical conditions and has demonstrated a high level of safety, very good tolerability and a strong activity in controlling free radicals, oxidative stress, microcirculatory alterations, oedema and different levels and causes of inflammation (1-21).



The explanation of its positive effects on cognitive function and attention in other studies (22,23) has indicated that a combined anti-inflammatory action, anti-oxidative and possibly enhanced microcirculation action may be the basis of cognitive enhancement. Studies have also shown that this compound reduces C-reactive protein levels and strongly controls plasma-free radicals (PFR) (24). The same studies indicated that patients treated for at least 4-6 weeks improve both their physical performance and their mental attitude and mood. (24,25) The strong, anti-oedema action may also be involved in improving mental functions as observed in flight studies during/after which subjects with peripheral and subclinical cerebral oedema had shown decreased attention, signs of jet-lag, desynchronization and generally altered cerebral functions. The alterations in cerebral functions – possibly associated with oedema had been almost completely prevented by pine bark extract use. (26)


Attention and memory

One study (22) has indicated that supplementation along with ginkgo biloba may acutely improve attention and memory in young, healthy students in tests of attention, memory and executive function. Sustained attention, episodic and working memory, mental flexibility and planning were evaluated in association with mood rating scales. Acute oral treatment

with ginkgo improved sustained-attention and pattern-recognition memory tasks.  This model study was repeated with pine bark extract (27) to evaluate cognitive function, attention and mental performance in normal students treated for 8 weeks. The supplement was used with the aim of enhancing “normal” mental performance. Attention, memory, and evaluation of executive functions were included. Students were also evaluated according to results of actual university tests. Oral administration improved sustained attention, memory, executive function and mood ratings. Actual performance on university tests indicated significantly better results in the treated group. This study therefore indicated a potential role for improving cognitive function in normal students.


Professional executive skills

A later 12-week, product-evaluation registry study aimed to evaluated the effects of supplementation in healthy professionals with high oxidative stress (28,29) and measure improvement in: cognitive function; attention; mental performance in a professional context; and oxidative stress (by measuring plasma free radicals). At the end of the registry period a group of 30 professionals used pine bark extract and an equivalent group of 29 professionals acted as controls.  There was an improvement in both groups, but in pine bark subjects the improvement was more significant than in controls (P<0.05). With pine bark, both subjective and objective measurements were improved.  Oxidative stress was significantly decreased (-30.4%) at 12 weeks in pine bark subjects in comparison with a non-significant variation observed in controls (+0.9%; difference between groups: P<0.05). In the cognitive test battery (PASAT, pattern recognition memory, spatial recognition memory, spatial working memory, IDED, Stockings of Cambridge), pine bark subjects showed a small but significant (P<0.05) improvement. Mood parameters including alertness, anxiety and contentedness significantly improved on average in professionals using the supplement (P<0.05) in comparison with controls (no significant change). In the evaluation of the 12 daily tasks, all items in the questionnaire were improved (P<0.05) with pine bark supplementation at the end of the study in comparison with controls. While the variations observed with the cognitive test battery are related to daily activity, the evaluation of cognitive functions and the evaluation of professional daily tasks could offer a better evaluation of professional performance. At inclusion scores for semi-professional minitasks were comparable in both groups. At 12 weeks the score was unchanged in controls but it was statistically significantly improved in pine bark subjects. Tolerability and compliance were optimal with >94% of the doses of supplement correctly used. At the end of the observation period there was a request to continue pine bark in 75% of the subjects that had used it. This study indicates that the same professionals with normalized oxidative stress tend to perform better on professional tasks. Several studies have indicated the important role of oxidative stress both in risk conditions and in preclinical diseases. (30-31). This is the first observation evaluating the effects of increased oxidative stress in otherwise healthy professionals (32).



1. Belcaro G, Cesarone MR, Errichi BM, Ledda A, StuardS, Dugall,M. Venous ulcers: microcirculatory improvement and faster healing with local use of Pycnogenol. Angiology 2005;56:699-705.

2. Blazsó, G.,Gábor,M.,Schönlau,F.,Rohdewald,P. Pycnogenol® accelerates wound healing and reduces scar formation. Phytother. Res 2004;18;579-81.

3. Calliste CA,Trouillas P, Allais DP, Duroux JL. Castaneas ativa Mill. leaves as new sources of natural antioxidant: an electronic spin resonance study. J Agric Food Chem 2005;53:282-8.

4. Canali R, Comitato R, Schonlau F, Virgili F.The anti-inflammatory pharmacology of Pycnogenol® in humans involves COX-2 and 5-LOX m RNA expression in leukocytes. Int. Immunopharmacol 2005;9;1145-9.

5. Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ippolito E, Scoccianti M et al. Prevention of edema in long flights with Pycnogenol. Clin Appl Thromb Hemost 2005;11:289-4.

6. Cesarone MR, Belcaro G, Rohdewald P, Pellegrini L, Ledda A, Vinciguerra G et al. Rapid relief of signs/symptoms in chronic venous microangiopathy with Pycnogenol: a prospective, controlled study. Angiology 2006;57;569-76.

7. Devaraj S, Vega López S, Kaul N, Schönlau 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;37:931-4.

8. Grimm T, Schäfer A, Högger P. Antioxidant activity and inhibition of matrix- metalloproteinases by metabolites of maritime pine bark extract (Pycnogenol®). Free Radical Biol Med 2004;36:811-22.

9. Grimm T, Skrabala R, Chovanova Z, Muchova J, Sumegova K, Liptakova A et al. Single and multiple dose pharmacokinetics of maritime pine bark extract (Pycnogenol®) after oral administration to healthy volunteers. BMCClin. Pharmacol 2006;6:1-12.

10. Grimm T, Chovanová Z, Muchová J, Sumegová K, Liptáková A, Duracková Z et al. Inhibition of NF-kB activation and MMP-9 secretion by plasma of human volunteers after ingestion of maritime pine barkextract (Pycnogenol®®). J Inflamm 2006;3;1-15.

11. Koch R.Comparative study of Venostasin® and Pycnogenol® for treatment in chronic venous insufficiency. Phytother Res 2002;16:1-5.

12. Petrassi C, Mastromarino A, Spartera C. Pycnogenol® in chronicvenous insufficiency. Phytomedicine 2000;7;383-8.

13. Belcaro G, Cesarone MR, Errichi S, Zulli C, Errichi BM, Vinciguerra G. Treatment of osteoarthritis with Pycnogenol®. The SVOS (San Valentino Osteo-arthrosis Study). Evaluation of signs, symptoms, physical performance and vascular aspects. Phytother Res 2008;22:518-23.

14. Belcaro G, Cesarone MR, Errichi S, Zulli C, Errichi BM, Vinciguerra G et al. Variations in C-reactive protein, plasma free radicals and fibrinogen values in patients with osteoarthritis treated with Pycnogenol. Redox Rep 2008;13:271-6.

15. Hu S. Dugall M. Mood and Pycnogenol Data on file;2012

16. Putter M, Grotemeyer KHM, Wurthwein G, Araghi-Niknam RR, Watson RR, Rohdewald P.Inhibition of smoking-induced platelet aggregation by aspirin and Pycnogenol. Thromb Res 1999;95;155-61.

17. 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;40;158-68.

18. Schmidtke I, Schoop W. Das hydrostatische Ödemunds eine medikamentöse Beeinflussung. SwissMed 1984;6:67-9.

19. USP, 2005. Maritime pine extract. In: United States Pharmacopoeia, US Pedition 28. United States Pharmacopeial Convention, Inc.; Rockville 2005; p. 2115-6.

20. Vinciguerra G, Belcaro G, Rohdewald P, Stuard S, Ricci A. Cramps and muscular pain: prevention with Pycnogenol in normal subjects, venous patients, athletes, claudicants and in diabetic microangiopathy. Angiology 2006;57:331-9.

21. Williamson G, Manach C. Bioavailability, bioefficacy of polyphenols in humans. II. Review of 93 studies. Am J Clin Nutr 2005;81:243-55.

22. Elsabagh S, Hartley DE, Ali O, Williamson EM, File SE. Differential cognitive effects of Ginkgo biloba after acute and chronic treatment in healthy young volunteers. Psychopharmacology (Berl). 2005;179:437-46.

23. Luzzi R, Belcaro G, Zulli C, Cesarone MR, Cornelli U, Dugall M, Hosoi M et al. Pycnogenol supplementation improves cognitive function, attention and mental performance in students. Panminerva Med 2011;53(3 Suppl 1): 75-82

24. Belcaro G, Cesarone MR, Steigerwalt RJ, Di Renzo A, Grossi MG, Ricci A et al. Jet-lag: prevention with Pycnogenol. Preliminary report: evaluation in healthy individuals and in hypertensive patients. Minerva Cardioangiol 2008;56(5 Suppl):3-9.

25. Cornelli U, Belcaro G, Ledda A, Feragalli B. Activity of some physiological modulators in reducing the side effects of levothyroxine in patients suffering from primary hypothyroidism. Panminerva Med 2011;53(3 Suppl 1):99-103.

26. Cornelli U, Belcaro G, Ledda A, Feragalli B. Oxidative stress following administration of levothyroxine in subjects suffering from primary hypothyroidism. Panminerva Med 2011;53(3 Suppl 1):95-8.

27. Cesarone MR, Belcaro G, Carratelli M, Cornelli U, De Sanctis MT, Incandela L et al. A simple test to monitor oxidative stress. Int Angiol 1999;18:127-30

28. Maxwell C. Clinical research for all. Oxford: Oxford University Press; 1989.

29. Campise M, Bamonti F, Novembrino C, Ippolito S, Tarantino A, Cornelli U et al. Oxidative stress in kidney transplant patients. Transplantation 2003;76:1474-8.

30. Incandela L, Belcaro G, Cesarone MR, De Sanctis MT, Griffin M, Cacchio M et al. Oxygen-free radical decrease in hypertensive patients treated with lercanidipine. Int Angiol 2001;20:136-40.

31. Cornelli U. Antioxidant use in nutraceuticals. Clin Dermatol 2009 Mar-Apr;27:175-94

32. Belcaro, G., et al. "Pycnogenol® improves cognitive function, attention, mental performance and specific professional skills in healthy professionals age 35–55." J Neurosurg Sci 58.4 (2014): 239-248.