James Greenblatt, MD, Jennifer Dimino, Winnie T. Lee

Introduction

It was 1534, and the crew of French explorer Jacques Cartier were in trouble. They had been ship-bound for months and surviving off meagre rations during their exploration of the eastern Canadian coastline for what would become the French empire’s vast claims to North America. The inevitabilities of life at sea had caught up with them in devastating fashion: Cartier’s men had scurvy. For many seafaring adventurers in that Age of Exploration, the cumulative effects of scurvy were intensifying and worsening preludes to a horrible disease, and often death. Vasco da Gama had lost two-thirds of his crew to scurvy in 1499, and in 1520, while attempting a trans-Pacific voyage, Ferdinand Magellan watched his ranks thin by 80% as scurvy claimed the lives of his men (Lamb, 2011).t was 1534, and the crew of French explorer Jacques Cartier were in trouble. They had been ship-bound for months and surviving off meagre rations during their exploration of the eastern Canadian coastline for what would become the French empire’s vast claims to North America. The inevitabilities of life at sea had caught up with them in devastating fashion: Cartier’s men

However, it seems that luck was on Cartier’s side, as he had befriended a tribe of Quebecois Native Americans in his explorations. Wise in the plant lore of their ancestors, they offered Cartier and his men a medicinal tea brewed from the needles and bark of special pine trees. To Cartier, the healing of his crew surely was not insignificant, and his journal entries are testament to the fact that this mysterious tea saved his men. The ramifications of the Quebecois’ kindness also led to one of the most exciting breakthroughs in the field of nutritional psychiatry: the ancient wisdom of the Native Americans shared with Jacques Cartier in the 1500s has been shown by modern science to be an effective treatment for attention-deficit/hyperactivity disorder (ADHD).

A Traditional Look at ADHD

According to data from the Centers for Disease Control and Prevention (2017), an estimated 6.4 million children aged 4 to 17 are diagnosed with ADHD at some point in their lives, reflecting a 41% increase in the last decade alone. ADHD is characterized by an ongoing pat- tern of inattention and/or hyperactivity–impulsivity that interferes with an individual’s functioning and development. Despite the thousands of scientific research papers published on the illness and diagnosis of ADHD, the etiology and treatment recommendations from medical and psychiatric professionals have changed little over the years.

The prevalence of ADHD today has given rise to wide- spread professional and public awareness, as well as a myriad of treatment approaches ranging from behavioral to pharmaceutical, while the  concomitant  surge in research churns out new scientific  data  that  seem to upend every firmly held assumption on which these treatments have been based. Studies from around the globe are  impressively  united  in  their  contradiction  of the long-held belief that ADHD is a “kids’ disorder”. While ADHD typically manifests before puberty, new research has revealed that the disorder is lifelong, with prevalence rates amongst adults being nearly identical to those observed in children.

Perhaps most fascinating is the ongoing research exploring the genetic and biologic underpinnings of ADHD. While parents are primarily concerned with the behavioral manifestations of ADHD and strategies for symptom management, researchers have identified multiple biological changes associated with the behavioral and cognitive issues associated with ADHD. There is a growing body of unequivocal empirical evidence that validates ADHD as a neurologic, brain-based disorder represent- ed by numerous biological abnormalities, so that what is observed as atypical behavior is merely the tip of a very large ADHD iceberg, the base of which can extend to an individual’s genetic blueprint and biochemical makeup. A comprehensive list of the neurobiological changes that have been found to be associated with ADHD exceeds the scope of this article; however, a sampling of such a list would include the following:

  • Several studies employing magnetic resonance imaging (MRI) technology have revealed abnormalities within the motivational circuitry of individuals with ADHD (Seymour, Reinblatt, Benson, & Carnell, 2015); neuroimaging studies have found unusual patterns of brain activation in individuals with ADHD, particularly within those net- works involved in reward
  • A study examining the volume and quality of electrochemical signaling (communication) be- tween brain regions found that ADHD children had atypical functional connections as compared with non-ADHD children (Costa Dias et al., 2013).
  • Studies have revealed a genetic component to ADHD susceptibility; recent research investigating the incidence of ADHD amongst family members has yielded a heritability estimate of 76% in the general population (Faraone et al., 2005).
  • Individuals with ADHD consistently display neurologic symptoms characteristic of insufficient dopamine. Dopamine plays a critical role in brain functions such as movement, attention, learning, and the reinforcing effects of many drugs. Re- searchers found that by administering a drug that enhances the release of dopamine in the brain of ADHD patients, symptoms were significantly relieved, thus confirming that ADHD symptoms are associated with insufficient dopamine (Carlson, 2014).
  • In our clinic, we have found many nutritional and metabolic disturbances related to the symptoms of ADHD, such as heavy metal toxicity, fatty acid imbalances, deficiencies of magnesium, iron, and zinc, and carbohydrate intolerance.

ADHD Medication Side Effects

The emerging research on the pathophysiology and neurobiology of ADHD has consequently forced us to reexamine the ways in which we approach ADHD treatment. No longer can ADHD be thought of as a behavioral disorder. We now know that ADHD involves changes and functional abnormalities in specific brain regions, brain networks, biochemical processes, and even systemic metabolic processes. A disorder this complex requires a treatment approach that is equally multi- faceted. Unfortunately, however, the reigning ADHD therapeutic paradigms utilized today are largely one-dimensional.

The administration of stimulant medications has long been the first-line treatment for ADHD, and drugs such as methylphenidate and dextroamphetamine are commonly prescribed to children as young as 3 or 4 years old to control restlessness, agitation, and impulsivity. By stabilizing dopamine levels in the brain, stimulants can affect an ADHD patient’s scholastic performance and social functioning, and they have been successful at improving grades, self-esteem, and social relationships. Although the administration of pharmaceutical drugs treats the symptoms of the disorder, it fails to address the causes of ADHD. For some, the eradication of  “problem behaviors” in the ADHD child is sufficient; yet stimulant medications range from parent training, psychotherapy, medications, neurofeedback, and behavior therapy, some of which have been proven effective. Methods such as neurofeedback target imbalances and cognitive abnormalities that underlie adverse ADHD symptomatology.

OPCs for the Treatment of ADHD: A Functional Medicine Approach

If we return to the 1500s, we now know that Cartier’s men were actually given a natural compound by the Quebecois that is found to have significant neurophysiological properties that improve symptoms observed in ADHD. These plant-derived compounds are known as oligomeric proanthocyanidins (OPCs), and while it may be premature for us to call them a miracle cure, mounting empirical evidence demonstrates that OPCs are a safe, natural, and efficacious treatment strategy in supporting cognitive function in clients with ADHD. To the ADHD patient, practitioner or parent, OPCs are a beacon of hope, substantiated by modern science to effectively address many of the root biologic causes of ADHD.

Science has demonstrated that OPCs directly benefit brain networks, neuron-to-neuron signaling, biochemical changes and metabolic processes that have been identified as underlying factors for many of the symptoms of ADHD. While it is speculative just how exactly OPCs improve cognitive function among individuals with ADHD, the available literature supports OPCs as a safe, naturally occurring, and therapeutic adjunct treatment that can improve cognitive performance and minimize the hallmark ADHD symptoms of hyperactivity and inability to focus. Their use as medicine over thou- sands of years is testament to their efficacy and safety, and modern research has corroborated that they are in- deed effective and safe.

In over three decades of using OPCs to treat patients with ADHD, we have never observed any negative side effects associated with OPC supplementation. Instead, we have observed patients whose thinking becomes progressively clearer once they start taking OPCs. Count- less patients have also reported an improved ability to concentrate and maintain focus, a steady improvement in their ability to read, write, and listen, and parents of patients have shared anecdotal stories about improvements in behaviors at home and performance in school.

The emerging research on the pathophysiology and neurobiology of ADHD is forcing us to reexamine the ways in which we approach ADHD treatment. Thanks to Jacques Cartier and Jacques Masquelier, OPCs are available to today’s mental health professional to offer to his or her ADHD patient as a viable augmentation strategy for relief of their ADHD symptoms.

About the Authors

James M. Greenblatt, MD, is the author of Finally Focused: The Breakthrough Natural Treatment Plan for ADHD that Restores Attention, Minimizes Hyperactivity, and Helps Eliminate Drug Side Effects (with Bill Gottlieb, Harmony Books, 2017). He currently serves as Chief Medical Officer and Vice-President of Medical Services at Walden Behavioral Care, and he is an Assistant Clin- ical Professor of Psychiatry at Tufts University School of Medicine and Dartmouth Geisel School of Medicine. An acknowledged expert in integrative medicine, Dr. Greenblatt has lectured throughout the United States on the scientific evidence for nutritional interventions in psychiatry and mental illness.

Jennifer C. Dimino, MS (Psychology), is a freelance writer who has produced blogs and consumer articles for Dr. Greenblatt’s new book Finally Focused (Harmony Books, 2017). She has specific research interests in inte- grative and holistic psychology and neuroscience.

Winnie T. Lee, RN, has provided research and edito- rial assistance for several book publications by James Greenblatt, including Finally Focused (Harmony Books, 2017), Answers to Binge Eating (with Virginia Ross-Tay- lor, 2014), and Integrative Therapies for Depression (edited by James Greenblatt & Kelly Brogan, CRC Press, 2016). She is a coauthor (with James Greenblatt) of Breakthrough Depression Solution: Mastering Your Mood with Nutrition, Diet and Supplementation (2nd ed., Sunrise River Press, 2016). She is currently pursuing a master’s in nursing to become a psychiatric nurse practitioner.

References

  1. Ahn, S. H., Kim, H, J., Jeong, I., Hong, Y. J., Kim, M. J., Rhie, D. J., . . . Yoon, S. H. (2011). Grape seed proanthocyanidin extract inhibits glutamate-induced cell death through inhibition of calcium signals and nitric oxide formation in cultured rat hippocampal neurons.  BMC  Neuroscience,  12,  78.  doi:10.1186/1471-2202-12-78
  2. Arnold, L. E., & DiSilvestro, R. A. (2005). Zinc in attention-deficit/hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology, 15, 619–627. doi:10.1089/cap.2005.15.619
  3. Arnold, L. E., Disilvestro, R. A., Bozzolo, D., Bozzolo, H., Crowl, L., Fernandez, S., . . . Joseph, E. (2011). Zinc for attention-deficit/hyperactivity disorder: Placebo- controlled double-blind pilot trial alone and combined with amphetamine. Journal of Child and Adolescent Psychopharmacology, 21, 1–19.
  4. Bilici, M.,Yildirim, F., Kandil, S., Bekaroğlu, M.,Yildirmiş, S., Değer, O., . . . Aksu, H. (2004). Double-blind, placebo controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Progress in Neuropsychopharmacology & Biological Psychiatry, 28, 181–190. doi:10.1016/j.pnpbp.2003.09.034
  5. Boris, M., & Mandel, F. S. (1994). Foods and additives are common causes of the attention deficit hyperactivity disorder in children. Annals of Allergy, 72, 462–468.
  6. Bowtell, J. L., Aboo-Bakkar, Z., Conway, M., Adlam, A. R., & Fulford, J. (2017). Enhanced task related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation. Ap- plied Physiology, Nutrition, Metabolism. Advance on- line publication. doi:10.1139/apnm-2016-0550
  7. Carlson, N. R. (2014). Foundations of behavioral neuroscience (9th ed.). Upper Saddle River, NJ: Pearson Edu- cation.
  8. Carper, J. (1998). Miracle cures: Dramatic new scientific discoveries revealing the healing power of herbs, vitamins, and other natural remedies. New York, NY: HarperPerennial.
  9. Centers for Disease Control and Prevention. (2017, February 14). Attention deficit/hyperactivity disorder (ADHD). Retrieved from https://www.cdc.gov/ncb– ddd/adhd/data.html.
  10. Chaudhary, A. K., Ahmad, S., & Mazumder, A. (2013). Cognitive enhancement in aged mice after chronic administration of Cedrus deodara Loud. and Pinus roxburghii Sarg. with demonstrated antioxidant properties. Journal of Natural Medicines, 68, 274–83. doi:10.1007/s11418-013-0775-y
  11. Chovanová, Z., Muchová, J., Sivonová, M., Dvorák- ová, M., Zitnanová, I., Waczulíková, I., . . . Dura- cková. Z. (2006). Effect of polyphenolic extract, Pycnogenol, on the level of 8-oxoguanine in children suffering  from  attention  deficit/hyperactivity disorder. Free Radical Research, 40, 1003–1010. doi:10.1080/10715760600824902
  12. Comim, C. M., Gomes, K. M., Réus, G. Z., Petronilho, F.,Ferreira, G. K., Streck, E. L., . . . Quevedo, J. (2014). Methylphenidate treatment causes oxidative stress and alters energetic metabolism in an animal model of attention-deficit hyperactivity disorder. Acta Neuropsychiatrica, 26, 96–103. doi:10.1017/neu.2013.35
  13. Costa Dias, T. G., Wilson, V. B., Bathula, D. R., Iyer, S. P., Mills, K. L., Thurlow, B. L., . . . Fair, D. A. (2013). Re- ward circuit connectivity relates to delay discounting in children with attention-deficit/hyperactivity disor- der. European Neuropsychopharmacology, 23, 33–45. doi:10.1016/j.euroneuro.2012.10.015
  14. Duric, N. S., Assmus, J., Gundersen, D., & Elgen, I. B. (2012). Neurofeedback for the treatment of children and adolescents with ADHD: A randomized and con- trolled clinical trial using parental reports. BMC Psychiatry, 12, 107. doi:10.1186/1471-244X-12-107
  15. Dvoráková, M., Sivonová, M., Trebatická, J., Skodácek, I., Waczuliková, I., Muchová, J., & Duracková, Z. (2006). The effect of polyphenolic extract from pine bark, Pycnogenol, on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD). Redox Report, 11, 163–72. doi:10.1179/135100006X116664
  16. Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., & Sklar, P. (2005). Molecular genetics of attention-deficit/hyperactivity disorder. Biological Psychiatry, 57, 1313–1323.
  17. Fuhrman, B., Lavy, A., & Aviram, M. (1995). Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. The American Journal of Clinical Nutrition, 61, 549–554.
  18. González-Castro, P., Cueli, M., Rodríguez, C., García, T., & Álvarez, L. (2016). Efficacy of neurofeedback ver- sus pharmacological support in subjects with ADHD. Applied Psychophysiology and Biofeedback, 41, 17–25. doi:10.1007/s10484-015-9299-4
  19. Greenblatt, J. M. (1999). Nutritional supplements in ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 1209–1211.
  20. Greenblatt, J. M. (2016, March). Oligomeric proanthocyanidins as an alternative treatment for ADHD. Integrative Medicine for Mental Health. Retrieved from http://www.integrativemedicineformentalhealth.com/articles/greenblatt_oligomeric_proanthocyanidins.html
  21. Heimann, S. W. (1999). Pycnogenol for ADHD? Journal of the American Academy of Child and Adolescent Psychiatry, 38, 357–358.
  22. Johansson, J., Landgren, M., Fernell, E., Vumma, R., Åhlin, A., Bjerkenstedt, L., & Venizelos, N. (2011). Al- tered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): An in vitro study. Behavioral and Brain Functions, 7, 40. doi:10.1186/1744-9081-7-40
  23. Karege, F., Perret, G., Bondolfi, G., Schwald, M., Bertschy, G., & Aubry, J. (2002). Decreased serum brain-derived neurotrophic factor levels in major de- pressed patients. Psychiatry Research, 109, 143–8.
  24. Kodoma,G., Fujisawa,C., & Bhadhprasit,W. (2012). Inher- ited copper transport disorders: Biochemical mechanisms, diagnosis, and treatment. Current Drug Metabolism, 13, 237–250. doi:10.2174/138920012799320455
  25. Lamb, J. (2011, February 17). Captain Cook and the scourge of scurvy. BBC History. Retrieved from http:// www.bbc.co.uk/history/british/empire_seapower/ captaincook_scurvy_01.shtml
  26. Luzzi, R., Belcaro, G., Zulli, C., Cesarone, M. R., Cornelli, U., Dugall, M., . . . Feragalli, B. (2011). Pycnogenol® supplementation improves cognitive function, attention and mental performance in students [Supplemental material]. Panminerva Medica, 53, 75–82.
  27. Mann, C., Lubar, L. F., Zimmerman, A. W., Miller, C. A., & Muenchen, R. A. (1992). Quantitative analysis of EEG in boys with attention-deficit-hyperactivity disorder (ADHD): A controlled study with clinical implications. Pediatric Neurology, 8, 30–36.
  28. Meisel, V., Servera,  M.,  Garcia-Banda,  G.,  Cardo,  E., & Moreno, I. (2013). Neurofeedback and standard pharmacological intervention in ADHD: A randomized controlled trial with six-month follow-up. Biological Psychology, 94, 12–21. doi:10.1016/j.biopsy- cho.2013.04.015
  29. Passwater, R. A. (1991). Pycnogenol (proanthocyanidins). WholeFoods Magazine, 3, 83–98.
  30. Robert, A. M., Tixier, J. M., Robert, L., Legeais, J. M., & Renard, G. (2001). Effect of procyanidolic oligomers on the permeability of the blood-brain barrier. Pa- thologie Biologie, 49, 298–304. doi:10.1016/S0369-8114(01)00148-1
  31. Rubio, B., Boes, A. D., Laganiere, S., Rotenberg, A., Jeurissen, D., & Pascual-Leone,A. (2016). Noninvasive brain stimulation in pediatric attention-deficit hyper- activity disorder (ADHD): A review. Journal of Child Neurology, 31, 784–796. doi:10.1177/088307381561567
  32. Russo, A. J. (2010). Decreased serum Cu/Zn SOD associated with high copper in children with ADHD. Journal of Central Nervous System Disease, 2, 9–14.
  33. Schwartz, J. C. (2011). The histamine H3 receptor: From discovery to clinical trials with pitolisant. British Journal of Pharmacology, 163, 713–721. doi:10.1111/j.1476- 5381.2011.01286.x
  34. Serafini, M., Maiani, G., & Ferro-Luzzi, A. (1998). Alcohol- free red wine enhances plasma antioxidant capacity in humans. The Journal of Nutrition, 128, 1003–1007.
  35. Seymour, K. T., Reinblatt, S. P., Benson, L., & Carnell, (2015). Overlapping neurobehavioral circuits in ADHD, obesity, and binge eating: Evidence from neuroimaging research. CNS Spectrums, 20, 401–411. doi:10.1017/S1092852915000383
  36. Shin, D. W., Kim, E. J, Oh, K. S., Shin, Y. C., & Lim, S. W. (2014). The relationship between hair zinc and lead levels and clinical features of attention-deficit hyper- activity disorder. Journal of Korean Academy of Child and Adolescent Psychiatry, 25, 28–36. doi:10.5765/jkacap.2014.25.1.28
  37. Steiner, N. J., Frenette, E. C., Rene, K. M., Brennan, R. T., & Perrin, E. C. (2014). In-school neurofeedback train- ing for ADHD: Sustained improvements from a randomized control trial. Pediatrics, 133, 483–492. Retrieved from http://pediatrics.aappublications.org/ content/pediatrics/early/2014/02/11/peds.2013-2059.full.pdf
  38. Szewczyk, B., Kubera, M., & Nowak, G. (2011). The role of zinc in neurodegenerative inflammatory pathways in depression. Progress in Neuropsychopharmacology and Biological Psychiatry, 35, 693–701. doi:10.1016/j. pnpbp.2010.02.010
  39. Takeda, A., Sakamoto, K., Tamano, H., Fukura, K., Inui, N., Suh, S. W., . . . Yokogoshi, H. (2011). Facilitated neurogenesis in the developing hippocampus after intake of theanine, an amino acid in tea leaves, and object recognition memory. Cellular and Molecular Neurobiology, 31, 1079–88. doi:10.1007/s10571-011-9707-0
  40. Toomim, H., Mize, W., Yeekwong, P., Toomim, M., Marsh, R., Kozlowski, G. P., & Remond, A. (2004). Intentional increase of cerebral blood oxygenation using hemoencephalography: An efficient brain exercise therapy. Journal of Neurotherapy, 8, 5–21. doi:10.1300/J184v08n03_02
  41. Uhlig, T., Merkenschlager, A., Brandmaier, R., & Egger J. (1997). Topographic mapping of brain electrical activity in children with food-induced attention deficit hyperkinetic disorder. European Journal of Pediatrics, 156, 557–561.