After over a year of extensive research and experimentation, a small cohort of individuals diagnosed with Parkinson’s disease effectively conducted a 6-week investigation utilizing a specially formulated Broccoli seed tea aimed at mitigating oxidative stress in neurons. This article provides the scientific background for the study and elucidates the rationale behind their decision to explore this potentially disease-mofifying treatment. Additionally, there are two documents available that offer further insight into this experiment.

You can learn about HOW this study was carried out and the results obtained, by downloading this short technical note: “The broccoli seed tea experiment – results and interpretation”.

A fully-developed scientific article is also available which you can download in PDF format by clicking on: “Pilot study of broccoli seed tea by Parkinson’s Patients”

Background: There is compelling evidence from leading researchers supporting the hypothesis that age-related divergence from normal redox balance in brain cells is a contributing factor in the development of Parkinson’s disease. This divergence leads to excessive oxidative stress and inflammation, which in turn damages cells and disrupts neuronal function. The equilibrium between oxidants and antioxidants is governed by the transcription factor Nrf2, known as the master regulator of antioxidant responses. However, the activity of Nrf2 declines with age, leading to greater levels of oxidative stress.

The isothiocyanate sulforaphane, derived from broccoli seeds, has the potential to stimulate Nrf2 and alter the redox equilibrium.

After receiving a diagnosis of Parkinson’s disease in 2018, I chose to explore this concept by closely monitoring my own symptoms in reaction to treatment with a specially-prepared broccoli seed extract. Following a period of 12 months dedicated to experimentation, I disclosed my findings and approaches to a smlall group of Parkinson’s patients who expressed interest in trialing the method themselves. This is their narrative.

The hypothesis regarding the potential benefits of sulforaphane for Parkinson’s disease had not been tested by official clinical trials. However, a small cohort of Parkinson’s disease patients has independently shown that a broccoli seed tea containing sulforaphane can alleviate their symptoms. This study provides compelling evidence that non-motor symptoms are significantly improved by this treatment, while motor symptoms remain unchanged throughout the duration of the experiment.

The Redox Balance System

Over the past two decades, specialized research has revealed the intricate gene-based system utilized by cells to uphold the delicate equilibrium between oxidants and antioxidants within the cellular environment. It is now widely accepted that the set-point of this redox control system may deviate from the optimal range as individuals age, thereby increasing susceptibility to various chronic illnesses such as neurodegenerative diseases, cancer, and heart disease. The Redox Balance System (RBS) exerts its influence on all cells, with heightened activity observed in the brain, heart, urinary tract, gastrointestinal tract, and endocrine tissues. Its primary function involves the prompt identification and elimination of oxidizing molecules, free radicals (Reactive Oxygen Species (ROS), and Reactive Nitrogen Species (RNS)), as well as toxins that pose a threat to cell membranes, mitochondria, and DNA. The generation of ROS and RNS occurs automatically during the cellular energy production process involving glucose and oxygen. Brain cells, particularly dopamine-producing ones, exhibit higher energy consumption and subsequently generate more ROS than other cell types. The secondary role of the RBS involves counteracting excessive inflammation. While an excess of ROS and inflammation proves detrimental to cells, an insufficiency can also be detrimental, as both serve as the first line of defense against infection and cancer. The RBS is equipped with intrinsic regulatory mechanisms to adjust ROS and inflammation levels in response to changing conditions. Nevertheless, compelling evidence suggests that in the brain cells of individuals with Parkinson’s disease, this system fails to consistently maintain ROS and inflammation within the optimal range.

For a comprehensive scientific analysis of the underlying mechanisms and the potential of Brassica seed extracts in addressing the factors contributing to Parkinson’s disease, you can access the following resource: Role of the transcription factor Nrf2 and Redox Balance in Parkinson’s Disease

For the scientific community, the RBS is referred to as the Nrf2/Keap1/ARE pathway, named after its three key players involved in orchestrating this intricate process. It is crucial to understand that these names are acronyms for the three proteins, each with a specific and essential role in preserving the delicate redox balance.

• ARE (Antioxidant Response Elements) constitute enhancer sequences located in the promoter regions of DNA across all chromosomes. Upon activation, they trigger the mechanism for promoting the transcription of clusters of genes responsible for producing antioxidants, antioxidant enzymes, and anti-inflammatory cytokines, in order to combat oxidative stress and inflammation.
• Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) is a signaling molecule (transcription factor) that localizes and binds to ARE, initiating gene expression.
• Keap1 (Kelch-like ECH-associated protein 1) functions as the gatekeeper protein, regulating the flow of Nrf2 to ARE. It accomplishes this by responding to signals from 27 sensors within the protein that detect the presence of ROS, RNS, toxins, and electrophiles in cell in which it is active.

Under normal conditions, the Nrf2 protein binds to the protein dimer Keap1 in the cytoplasm and undergoes degradation. However, when Keap1 is oxidized by reactive oxygen species (ROS), electrophiles, or sulforaphane, newly synthesized Nrf2 migrates to the nucleus where it binds to ARE and facilitates the transcription of genes responsible for antioxidant and anti-inflammatory functions. Illustration based on the work of P. Hiebert and S. Werner.

Whenever Nrf2 binds to the ARE, the gene promoter function of ARE initiates the transcription of a wide array of genes to produce antioxidant and detoxifying enzymes, anti-inflammatory cytokines, and simultaneously suppress inflammatory cytokines. Cytokines are small messenger proteins that either generate or suppress inflammation. These genes play a crucial role in restoring a healthy environment inside each cell, enabling them to function properly. The production of these antioxidant and anti-inflammatory elements is contingent upon the quantity of Nrf2 present in the nucleus. Nrf2 is not active in neurons. Neurons depend on the activity of Nrf2 in astrocytes which are responsible for maintaining the health of neurons and mitochondria. One way to address this issue is to dampen the activity of the gatekeeper Keap1, allowing more Nrf2 protein to reach ARE and increase the expression of antioxidant molecules and enzymes. There are several natural molecules in food known to reduce the activity of Keap1, but they are not present in sufficient quantities in regular diets to effectively resolve this problem.

Calming down the Keap1 gatekeeper

It requires 2 molecules of Keap1 to form a dimer capable of capturing one Nrf2 molecule. Keap1 molecules act as regulators of the cellular redox environment. They assess the levels of reactive oxygen species (ROS) in the cell through 27 distinct sensors that identify the presence of oxidants and toxins. Higher levels of detected ROS result in more Nrf2 molecules being allowed to move to the nucleus, where they activate the antioxidant response element (ARE) and enhance the production of antioxidant enzymes and anti-inflammatory cytokines. If ROS levels are deemed low or satisfactory, Keap1 detains and degrades the Nrf2 molecules. This process is designed to maintain an optimal level of enzymes and cytokines for a healthy environment. In individuals with Parkinson’s disease, the redox balance regulator fails to maintain the ideal equilibrium, leading to excessively high ROS levels. Adjustment of the redox balance control system is necessary to restore the ROS balance within the range that supports neuronal health.

A potential explanation for the elevated levels of ROS could lie in the natural aging process. As we age, our cells produce less Nrf2 and more Keap1. This change in ratio results in a decreased flow of Nrf2 molecules to ARE, leading to less frequent activation of ARE and pushing the redox range towards a higher state of oxidative stress. Fortunately, several methods to inhibit Keap1 are known, allowing more Nrf2 to reach ARE. However, caution is necessary, as excessively boosting Nrf2 too quickly may trigger the system’s built-in mechanisms to counteract such surpluses. This activates a negative feedback loop, leading to the opposite effect, albeit with a delayed response.

One method to pacify Keap1 is by providing it with “soft oxidant” molecules known as electrophiles. Oxidation is the process in which an atom or molecule relinquishes an electron by transferring it to another atom or molecule. Potent oxidants like ROS aggressively and irreversibly take electrons from other tissues, causing damage. In contrast, electrophiles are milder and temporarily “borrow” electrons. They are strongly attracted to certain Keap1 sensors that possess electrons to lend. When a Keap1 sensor lends an electron, it triggers the process of deactivating its gatekeeping function. Cruciferous vegetables such as cabbage, broccoli, Brussels sprouts, mustard, and turnips contain the most active electrophiles in foods. These vegetables are renowned for their health benefits due to the presence of isothiocyanates, which also contribute to their strong taste that some may find unpleasant. There are over 50 different isothiocyanates in these plants, with sulforaphane being the most significant, found in high concentrations in the seeds or sprouts, as opposed to the small amounts present in the vegetable itself.

Can restoring the Nrf2 redox equilibrium contribute to the management of Parkinson’s disease?

Resetting the Nrf2 redox balance system has not been officially tested on individuals with Parkinson’s disease. Through my own experiments and observations, I have developed a protocol for the preparation and dosing of Brassica seed extracts, as well as a checklist for monitoring the progression of symptoms over weeks or months. Although the protocol is not without flaws, it was shared with a group of Parkinson’s disease patients in October 2020. A small subset of individuals chose to conduct self-experimentation by preparing their own broccoli tea and collaborating on data collection. The outcomes of this pioneering initiative are quite remarkable. They clearly indicate that a specific set of symptoms, collectively referred to as non-motor symptoms, exhibit a notable response to this treatment within just a few weeks, while motor symptoms show minimal change over this short timeframe.

Non-motor symptoms were strongly attenuated by broccoli seed tea whereas motor symptoms were largely unaffected.

Interesting, but what does this mean?

General fatigue emerged as the most pervasive non-motor symptom in the 8 participants with Parkinson’s disease who participated in the study. Every individual experienced general fatigue, and all 8 noted improvement or complete relief from fatigue at the conclusion of the 6-week trial. The overall fatigue score decreased by 90%.

Persistent fatigue, an overwhelming sensation of exhaustion unrelated to physical effort, stands as a poignant and prevalent symptom reported by Parkinson’s disease patients. It often manifests well before diagnosis and persists throughout the course of the disease. Despite its profound impact on the quality of life of PD patients, fatigue remains inadequately documented and researched. Notably, fatigue is also a characteristic symptom of mitochondrial disease, and indicators of heightened oxidative stress and mitochondrial dysfunction are closely linked to the severity of Chronic Fatigue Syndrome.

Taken together with prior knowledge, the findings of this study align with a more intricate model where mitochondria within dopaminergic neurons emerge as the predominant subject of oxidative stress, ultimately resulting in impaired energy generation in DA neurons.

Given the extensive body of experimental evidence linking oxidative stress to mitochondrial dysfunction and impaired energy production in DA neurons, the prevalence of fatigue experienced by individuals with Parkinson’s disease comes as no surprise. The reduction in fatigue observed in the participants of the broccoli seed tea study aligns with the theory that sulforaphane, through its activation of the Nrf2/ARE pathway and its neutralization of oxidative stress, plays a role in mitigating mitochondrial dysfunction and reinstating normal energy production in neurons. Furthermore, the relatively prompt onset of these effects seems to be in line with the kinetics of mitochondrial evolution and regeneration.

A theory for Parkinson’s Disease based on a cascade of two mechanisms suggests a complex interplay of factors contributing to the affliction’s pathogenesis.

If the aforementioned hypothesis holds true, it suggests that Parkinson’s disease advances through two distinct stages.

In the first step, oxidative stress leads to mitochondrial dysfunction, resulting in a decrease in energy production.
With progressive redox imbalance, mitochondria in highly exposed neurons are increasingly damaged by oxidative stress. This results in the impairment of the crucial Complex 1 enzyme within the mitochondria, which is essential for the conversion of glucose and oxygen into energy. The damage to Complex 1 leads to an automatic increase in ROS, perpetuating a vicious cycle that amplifies the process. As a consequence, these neurons undergo a reversible form of chronic mitochondrial dysfunction due to oxidative stress. Fatigue, a prevalent non-motor symptom of Parkinson’s disease, stands as the hallmark manifestation of mitochondrial dysfunction. Dopaminergic neurons, with their high energy demands, are particularly susceptible, although other types of neurons are also highly likely to be affected.

In the second step, dopaminergic neurons with energy deficiency are unable to maintain their usual dopamine production.

As their energy supply diminishes, a growing quantity of DA neurons experience decreased productivity and may ultimately cease functioning entirely. Over time, some of these neurons may perish. Consequently, dopamine levels will decrease to a point below the critical threshold for normal motor function, leading to the manifestation of motor symptoms. There is ample evidence to anticipate that this sequence of events will persist as the disease progresses.

A disease that advances through two distinct mechanisms demands a treatment strategy that tackles both processes. Existing therapies solely target the dopamine deficiency responsible for the motor symptoms of Parkinson’s disease. It is crucial to address the mitochondrial dysfunction and energy deficit resulting from oxidative stress to Complex 1 enzymes in all neuron types.

Albert F Wright