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From the Townsend Letter
October 2017

Optimizing Attention Deficit Hyperactivity Disorder (ADHD) Treatment with Oligomeric Proanthocyanidins (OPCs)
by James Greenblatt, MD, and Winnie T. Lee, RN
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Neuroprotective Properties of OPCs
There are several proposed mechanisms for age-related cognitive deficit in memory and learning. Animal studies have shown that oxidative stress within aging neurons can be modified with the neuroprotective effects of OPCs. In one study, OPCs decreased free radical damage and increased the activity of enzymes responsible for clearing these reactive-oxygen species among animals with deteriorated memory and learning abilities.13 New insights into ways of protecting the aging brain from memory deficits has led studies into the histological modification of vascular endothelial growth factor receptors (VEGFR) within the brain, a signal protein produced by cells that stimulates vasculogenesis and angiogenesis.14
Klaire LabsMoreover, several animal studies have shown the positive benefit of OPCs to affect mood and reduce depressive symptoms.15 In a double blinded, randomized, crossover study, patients with chronic fatigue syndrome had improved depression and anxiety symptoms after eight weeks of OPC rich polyphenol supplements.16 Another cross-sectional study of 42,093 Japanese adults aged greater than 40 years old from the general population reported that green tea was inversely associated with psychological distress even after adjustment for possible confounding factors.17 When solely looking at depressive symptoms, green tea was also associated with a lower prevalence in the Japanese community-dwelling older population.18

Bolstering the Blood-Brain Barrier
The blood-brain barrier (BBB) is a semipermeable barrier between the blood and brain that allows specific substances of a certain size and chemistry to pass through. The physical and functional integrity of the BBB is of paramount importance, as the BBB determines what molecules gain access to the brain itself. A healthy BBB is therefore essential for the regulation of biochemical, neurotransmitter, and micronutrient levels within the brain, as well as for the protection of brain cells against substances carried within the blood that may be potentially damaging (e.g., toxins, pollutants). 
Unlike many other antioxidants, OPCs have a strong affinity for collagen-elastin crosslinks present within the tight junctions of the BBB. This property allows OPCs to not only cross the BBB but also protect and maintain regulatory mechanisms present within the BBB. In vivo animal studies have shown that oral administration of OPC can greatly increase the resistance of brain capillaries to the hydrolytic action of bacterial collagenases injected into their lateral ventricles, sustaining the collagen cross-linking component of the basement membrane.19
The BBB also helps maintain physiologic molecules from leaking out of the brain for maintaining a proper homeostatic environment. One study evaluated fourteen boys (ages 6-12 years) with ADHD for deficiency in necessary brain chemicals.20 They found that ADHD patients had nearly 50% lower amino acid levels of tryptophan and much higher levels of alanine than normal brains. Decreased transport of tryptophan due to a dysfunctional blood-brain barrier can lead to a further deficiency in serotonin access in the brain that might cause disturbances in behavior and cognitive performance.
Maintaining the functional abilities of the blood-brain barrier is integral for protecting the brain from the penetrative harmful substances, such as environmental toxins leading to oxidative damage within the brain. The use of synthetic food additives (i.e., artificial coloring), made from petroleum, and preservatives (i.e., sodium benzoate) has increased by 500% over the past five decades. This increased use introduces children to the greatest foreign antigenic load, challenging their immune system. 
These dyes are naturally small and therefore able to easily evade the host immune response. Additionally, they are able to either bind body proteins to form immune complexes (Antigen-IgG) that are able to travel through an impaired BBB and deposit within the brain and/or peripherally mediate the release of histamine from mast cells and basophils. A double-blind placebo controlled food challenge was completed on 16 children and showed that on days with ingestion of reactive foods, their symptoms were significantly exacerbated when compared to placebo days.21  Another study on 15 patients suffering from food-induced ADHD employed topographic electroencephalographic (EEG) mapping to show that intake of provoking foods directly increased brain electrical activity in the fronto-temporal areas of the brain.22

Miracle-Gro for Neurons: Brain-Derived Neurotrophic Factor (BDNF)
Multiple research studies have demonstrated that OPCs will enhance the production of brain-derived neurotrophic factor (BDNF). BDNF is a protein found in the central and peripheral nervous system that plays an essential role in the growth, differentiation, and maturation of neurons, as well as developing and maintaining the connections between neurons.23 BDNF is a mediator of neuroplasticity, a term used to describe the brain's ability to reorganize itself in response to changing patterns of stimulation. BDNF activity is crucial in supporting the brain's ability to respond to novel demands, such as learning new information, being stimulated in a new way, or even adaptively adjusting to compensate for damage. Experimental studies have shown that consumption of OPC-rich foods such as green tea and dark chocolate increases BDNF levels. Adequate BDNF levels are critical for ADHD patients who might struggle with learning as a result of activational impairments in reward processing centers of the brain, or impaired electrochemical signaling between neural networks secondary to diminished functional connectivity.24 

Clinical Utility of OPCs in ADHD Treatment
There is no such thing as a 'universal fix' or 'magic bullet,' for any major neuropsychiatric illness.  Thanks to differences in genetic makeup, DNA expression, nutrition, physical activity, living environment, and patterns of social interactions, each and every individual ADHD patient is unique.  What works for one patient may not necessarily work for another, and OPCs may not be the solution for every person with ADHD. However, for many inattentive, distractible children (and adults), OPCs can be efficacious as an adjunct therapy, as we have evaluated the empirical data that confirms OPCs' ability to dramatically improve clinical symptoms of ADHD while minimizing the use of high-dose stimulant medications.
Science has demonstrated that OPCs directly benefit a host of brain regions, brain networks, systems of neuron-to-neuron signaling, biochemical and metabolic processes, and metabolic ratios that have been identified as being responsible for many of the symptoms of ADHD. There are several proposed theories about how OPCs can minimize symptoms of hyperactivity, improve focus, regulate mood lability, and even combat age-related cognitive decline. As a potent antioxidant, OPCs is involved in several roles that support neurotransmitter activity, neuronal growth, and immunological function. While we do not know the exact mechanism, the available literature supports OPCs as a safe, natural, and therapeutic alternative or adjunct treatment that can improve cognitive performance and minimize ADHD symptoms.
The use of OPC supplements has not only benefited patients with ADHD, but scientists have also found that they can be useful in combating depression and neurodegenerative diseases associated with the aging process by stimulating neuronal growth and enhancing the integrity of the blood-brain barrier.
In two decades of using OPCs to treat patients with ADHD, I have observed countless patients whose thinking becomes progressively clearer once they start taking OPCs. OPCs can be an effective biological alternative in the treatment of adults and children with ADHD. By incorporating them into modern-day nutritional psychiatry, we can offer countless patients relief from symptoms. 

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References .pdf

James M. Greenblatt, MD, is the author of Finally Focused: The Breakthrough Natural Treatment Plan for ADHD that Restores James M. Greenblatt, MDAttention, 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 Clinical 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.
For more information, visit

Winnie T. Lee, RN

Winnie T. Lee, RN, has provided research and editorial assistance for several book publications by James Greenblatt. 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 degree in nursing to become a psychiatric nurse practitioner.


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