Risk Factors for Parkinson’s Disease: What to Know

Parkinson’s disease (PD) is a common movement disorder affecting nearly one million people in the United States and 10 million worldwide. The death of neurons or nerve cells producing dopamine is the main cause of PD. The build-up of the protein alpha-synuclein in the brain, and occasionally in the gut, can also cause neurons to die.

The exact causes of the disorder are unclear, but researchers have identified several risk factors for Parkinson’s disease. The disease likely progresses unnoticed for many years before diagnosis, and the first signs of PD could be mistaken for other conditions or simply as part of aging. 

Yet, certain diet and lifestyle factors may help with nutrition and gut health deficits often associated with PD during the early stages. Recent research also suggests there may be ways to detect PD earlier, which could help with earlier treatment and control of health effects. 

Risk Factors for Parkinson’s Disease

Parkinson’s disease is complex and likely caused by several factors. In some cases, PD is spontaneous and develops for no clear reason. 

Environmental Risk Factors

Researchers have identified several environmental factors that may lead to the loss of nerve cells, causing a lack of dopamine. A large case-control study looked at factors that may increase the risk of or protect against developing PD. The most common environmental risks were exposure to toxins and dyspepsia.

Researchers believe that environmental factors or other medical conditions may contribute to disease development in those with or without a family history of PD. PD may also happen without any known cause for others.

The most common toxins PD patients have been exposed to include:

  • Oils 
  • General anesthetics
  • Metals
  • Pesticides

Heightened exposure to pesticides may lead to high alpha-synuclein levels in the brain. Contact with these toxins may result from professional or residential exposures, including rural living. Additionally, past head trauma, coffee consumption, cigarette smoking and low physical activity were associated with increased PD risk.

Genetic Factors

People who have a relative with PD have a three to four times higher risk of developing Parkinson’s disease. Genetic variations or mutations are thought to contribute an overall 25% risk. 

Researchers have identified more than 90 variants of key genes mostly linked to alpha-synuclein protein coding and mitochondria or energy center function in brain cells. Common genetic variants associated with PD were also often involved in signaling pathways associated with response to a stressor, which could be a toxin.

Mutations in some of these genes cause problems with how your body uses chemical messengers like dopamine. They also alter protein buildup and the body's ability to remove unstable molecules called free radicals. In addition, changes to alpha-synuclein’s SNCA gene likely contribute to early-onset Parkinson’s disease.

Sleep & Gut Disorders

Sleep and gut disorders may precede Parkinson's

Certain gut symptoms and sleep disorders are strongly associated with PD and may be risk factors for, or early signs of, Parkinson’s disease. About 80% of patients with PD have at least one digestive symptom throughout the disease, including nausea, constipation, and difficulty completing a bowel movement.

Constipation often happens before motor symptoms appear and worsens as the disease progresses. It’s considered one of the most significant prodromal (or early warning) symptoms and may occur as much as 20 years before a diagnosis.

One theory suggests PD may be linked to variations in the balance of bacteria and a buildup of alpha-synuclein aggregates in the gut that travels to the brain. 

Research also suggests that a medical history of rapid eye movement sleep behavior disorder (RBD) is a powerful predictor of Parkinson’s disease. RBD is a chronic sleep disorder that causes loss of rapid eye movement (REM) sleep, resulting in sleep paralysis in which one may experience dream enactment while asleep. Patients often report high injury rates to themselves and others during sleep because of violent movements. 

RBD is considered a prodromal symptom, or one of a few early signs of Parkinson’s disease. About 70% of patients with RBD will develop parkinsonism and alpha-synuclein aggregates in the brain within 12 years of diagnosis. About 40% of patients with PD also have RBD at the same time, suggesting the two conditions develop alongside each other. 

What Happens in the Early Stages of Parkinson’s Disease?

Long before motor symptoms of Parkinson’s disease appear, problems in the gut and/or brain may begin setting the stage. For some people, PD may start in the gut or digestive tract, while it begins in the brain for others. 

The gut and brain have a bidirectional relationship, which means the brain influences the digestive system and vice versa. Whether Parkinson’s begins in the digestive tract or the brain, most patients have symptoms in both

The exact progression and cause of the disease aren’t clear. However, patients have common characteristics: gut dysbiosis, alpha-synuclein accumulation, and loss of dopamine-synthesizing neurons in the substantia nigra, leading to dopamine deficiency and dopamine-signaling problems.  

Gut Dysbiosis

Gut dysbiosis is the imbalance of the bacteria in your gut, known as the microbiota or microbiome. Dysbiosis is associated with a few key features, such as:

  • Less diversity in the types of bacteria present
  • A loss of beneficial bacteria
  • An overgrowth of harmful bacteria

Some beneficial gut bacteria interact with your nervous system via the vagus nerve, which connects the gut and brain. Thus, microbiome changes can have an impact on brain health. 

In addition, the gut barrier can break down when dysbiosis occurs, allowing bacteria byproducts and food molecules to leak into your bloodstream and potentially cross the blood-brain barrier. This can lead to inflammation in the brain, and interference with brain signaling. 

Many people eventually diagnosed with PD have an altered microbiome and have gut problems before motor symptoms, such as tremors, appear.  Whether or not an altered microbiome can contribute to aggregation of alpha-synuclein within the gut is not known.

Alpha-Synuclein Protein Buildup

According to a recent cross-sectional study, α-synuclein is considered a biomarker and a molecular hallmark of Parkinson's disease. Clumps of alpha-synuclein protein (called Lewy bodies) in the substantia nigra region of the brain can cause a loss of key dopamine-producing nerve cells. 

The reason these protein clumps initially form is poorly understood. Three possible processes are hypothesized: (1) influence of toxic substances, (2) inflammatory processes, and (3) genetic variations which lead to more alpha-synuclein protein than usual. Overexpression of normal alpha-synuclein protein formation causes the protein to misfold, interferes with normal turn-over of the protein within cells, and contributes to the build-up of toxic aggregates. 

As mentioned above, a review of research indicates that PD patients also have alpha-synuclein aggregates or clumps in a variety of locations within the digestive tract. An early animal study showed that these proteins can travel to the brain via the vagus nerve where they can kill off dopamine-producing cells. 

How the aggregation of alpha-synuclein might be caused by, or give rise to, common non-motor prodromal symptoms such as gut dysbiosis/constipation, or loss of smell, or RBD is currently a matter of speculation.  

Loss of Dopamine

Loss of dopamine can make it harder to move

Parkinson’s disease is a dopamine deficiency disease. Dopaminergic cells die due to aggregation of alpha-synuclein or other reasons. Without these cells, your body doesn't make enough dopamine, affecting your movement, memory, mood, and cognitive ability. 

The degradation of common motor symptoms, like balance or fine motor control, begins to appear as the damage occurs. However, you may have experienced your first symptoms of Parkinson’s much earlier. 

Nutrients to Consider

Certain dietary deficiencies are common for people who also have Parkinson’s disease or early symptoms. Discuss vitamins, probiotics and herbs you’re considering taking with your doctor before taking them, in order to understand how they may affect you. 

Vitamin D

Vitamin D deficiency is common in PD patients, however studies conflict concerning whether or not low serum levels of vitamin D are associated with a higher risk of PD. It is also not known if taking vitamin D reduces the risk of developing Parkinson’s disease. 

Vitamin D can also be obtained from sun exposure, and plays a role in many essential processes such as production of bone, muscle strength, and immune function.

Vitamin B6 and B12

Studies suggest that higher levels of vitamin B6 in the diet over the long-term may reduce the risk of developing PD. B6 is involved in the synthesis of dopamine

While dietary intake of vitamin B12 has not been shown to reduce the risk of PD, B12 deficiency is common amongst PD patients. Many PD patients experience neuropathy, or nerve damage that causes muscle weakness, pain, numbness, tingling, and other sensations, which may be caused in part by B12 deficiency.  

Prebiotic Foods

Prebiotic fiber helps keep your gut and brain healthy

Prebiotic foods are high-fiber foods on which gut bacteria feed.  Prebiotics help encourage healthy growth, function, and balance of your microbiome. Fiber-rich prebiotics may also improve constipation and other gut symptoms associated with early PD.


Your body makes dopamine from the amino acids phenylalanine or tyrosine. These building blocks convert to a precursor form of dopamine which crosses your blood-brain barrier and further converts to dopamine in the brain. 

Some substances may help your body make or respond to dopamine and protect your brain from damage. Caffeine, for example, enhances dopamine signaling and protects dopamine-producing cells from degeneration. 

Mucuna pruriens is rich in dopamine precursor L-Dopa and may protect dopamine nerve cells from damage. Amino acids and adequate protein also provide your body with the building blocks for dopamine synthesis. 

PD patients taking L-dopa should consult with their health care provider before taking any substances that may increase dopamine levels to avoid a potentially negative drug interaction.

PS128 Probiotics

PS128 in Neuralli helps support gut-microbiome to brain signaling

Research suggests probiotics for Parkinson’s, such as L. plantarum PS128, may support gut-microbiome to brain signaling, resulting in higher dopamine levels. 

In a preclinical animal study, PS128 enhanced dopamine levels and eased motor deficits. PS128 also protected against the loss of dopamine-producing neurons in preclinical studies, suggesting a nutritional benefit for neurodegenerative disorders. 

2021 open label clinical study in PD patients noted that 12 weeks of PS128 alongside their anti-parkinsonian medication improved their quality of life and motor scores. While this research is in the early stages, the results are promising. 

Tests for Early Parkinson’s Disease Detection

Recent advances in research and medical testing may help identify PD earlier, allowing for earlier medical intervention, and perhaps more years of mild vs. advanced symptoms. New tests on the horizon include alpha-synuclein tests, smell tests, and ear EEG devices. However, many of these tests are still proof of concept studies and aren’t available yet from your doctor.

Alpha-Synuclein Seed Amplification Assay (a-Syn-SAA)

large analysis study of 1,123 patients looked for tiny amounts of alpha-synuclein aggregates in cerebrospinal fluid. Results suggest these tests are highly accurate and sensitive and can detect early cases of PD, even when motor symptoms are not yet present.  

Smell Test

Another important early sign of Parkinson’s is a loss of smell. Some experts think that for some people, PD might start in the olfactory bulb, the brain region responsible for your sense of smell. 

Protein may clump here and then travel to other brain regions, causing damage. A study funded by the Michael J. Fox Foundation is underway, examining whether smell tests may help accurately identify PD.

Ear EEG Sleep Monitoring

A Danish health technology company has partnered with a university to develop and test an ear EEG device for patients with PD and Alzheimer’s. The device will monitor sleep patterns and electrical activity in the brain to test whether the devices can help screen for these brain diseases.

Dietary Support for Parkinson’s Disease: Neuralli MP

Neuralli MP is the first gut-brain medical probiotic for the dietary support of neurological conditions such as PD. Preclinical studies suggest that the PS128 probiotic in Neuralli MP influences dopamine and serotonin levels, addressing the unique needs of PD. Ask your health care professional if Neuralli MP is right for you.


Recommended reading:

L. plantarum PS128 – Separating Psychobiotics from the Common Probiotic

Three Roles for Probiotics for Parkinson’s Disease

How to Get the Most out of Neuralli MP


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