High levels of iron — a mineral best known for supporting healthy blood and brain activity — may increase the risk of Parkinson’s disease and dementia, according to new research.
Iron plays a vital role in the body, helping produce hemoglobin, the protein in red blood cells that carries oxygen from the lungs to tissues and organs throughout the body.
Because the body cannot make iron on its own, people must get it through food. Common sources include animal proteins such as lean red meat, clams and oysters, as well as plant-based options including spinach, lentils, tofu and white beans.
Too little iron can also be harmful. Iron deficiency affects roughly one in seven Americans — about 36 million people — and has been associated with developmental problems and cognitive decline, in part because the mineral supports energy production and neurotransmitter function.
But scientists at the Salk Institute in California say their findings suggest there may be risks on the other end of the spectrum as well. Their research indicates that excess iron can gradually build up inside neurons, with the effects becoming more damaging later in life.
The researchers believe this buildup may weaken cells’ natural defenses, leaving them less able to withstand stress and more likely to die over time.
When nerve cells die in brain regions central to memory and thinking, including the hippocampus and cerebral cortex, it can contribute to dementia, a condition that affects about 7 million Americans.
Parkinson’s disease, which affects around 1 million Americans, is linked to the loss of dopamine-producing neurons that help control movement. The death of these cells may therefore play a role in the development or progression of the disease.
A new study found an accumulation of iron may lead to cell changes associated with dementia and Parkinson’s disease
The researchers noted that evaluating iron levels could be a key tool in preventing neurodegenerative diseases like dementia and Parkinson’s.
‘Resilience has become a huge topic of discussion when it comes to Alzheimer’s disease and other neurodegenerative disorders, trying to make the brain more resilient in the face of stressors that contribute to neurodegeneration,’ Dr Pam Maher, senior and co-corresponding study author and research professor at the Salk Institute, said.
‘Our study reveals that cells lose resilience when iron hits a certain level, making neurons more susceptible to stressors that damage or even kill them.’
The findings come as both dementia and Parkinson’s disease are on the rise in the US.
Experts estimate dementia diagnoses are expected to double by 2050.
The Parkinson’s Foundation estimates 1.2million Americans will be diagnosed with Parkinson’s by 2030, and 90,000 are struck by the disease every year.
This is an increase from the previously estimated rate of 60,000 a decade ago, the foundation estimates.
Recent research suggests environmental exposures like pollution and pesticides, along with growing rates of chronic conditions like obesity and diabetes, may be to blame, but scientists are still unraveling the causes.
Michael J Fox (pictured above at the 32nd Annual Actor Awards in March) was diagnosed with Parkinson’s disease in 1991, revealing his diagnosis in 1998. In 2000, he founded the Michael J Fox Foundation to help fund Parkinson’s research
The new study, published in the journal Cell Death Discovery, used human neural cells from the nervous system cancer neuroblastoma to compare the effects of acute and chronic iron exposure. Acute exposure lasted between six and eight hours, while chronic was about nine days.
Chronic exposure was meant to mimic slow accumulation that would be seen during aging.
Using the cell models, the researchers coined the new pathway chronoferroptosis. Ferroptosis is a well-studied phenomenon in which cell death is caused by a process called lipid peroxidation.
This occurs when harmful molecules called free radicals steal electrons from the lipids in cell membranes, resulting in cell damage.
In chronoferroptosis, however, that pathway doesn’t end in cell death.
Instead, neurons chronically exposed to iron saw long-term functional changes rather than immediate death. Acutely exposed neurons could handle the stress, but those with chronic exposure became vulnerable to neurodegenerative diseases.
‘We think these coordinated alterations in iron-handling and antioxidant defense proteins make chronically exposed neurons vulnerable to neurodegenerative pathology,’ Dr Nawab John Dar, co-corresponding study author and postdoctoral researcher in Maher’s lab, said.
‘Entering this state of chronoferroptosis may set neurons up for age-related failure.’
Iron cannot be produced by the body on its own, but it is rich in animal proteins like lean meat, fish and beef liver
Dar noted that by using the progressive model, the team found it’s ‘not the amount of iron that seals the fate of these cells, it’s the amount of time they spend under stress.’
‘It’s one of the most important minerals in the body,’ he added. ‘So, it isn’t the iron itself that is a problem with age. It is this accumulation of iron over time that is the problem.’
The researchers were able to treat the iron toxicity with Ferrostatin-1, a synthetic antioxidant that inhibits chronoferroptosis and blocks cell stress and death.
There were several limitations to the research, including not specifying an exact amount of iron that leads to chronoferroptosis and looking at cell models rather than humans.
