NEW YORK – A combination of nutrients offered protection against neurodegeneration in a rodent model of parkinsonism, according to a new study.
The findings pave the way for human studies to explore whether nutritional supplementation in early Parkinson’s disease (PD) can modify the disease course, said, speaking at the International Conference on Parkinson’s Disease and Movement Disorders.
The rodent study found improvement in a broad array of behavioral, biochemical, and histopathologic measures in rats who were dosed with a combination of whole foods known to have constituents beneficial in other disease states.
Dr. Ali, who is head of the department of pharmacology and toxicology at Al-Azzah University, Cairo, said that the element manganese ingested in excessive amounts is neurotoxic to both humans and rodents. Many elements of manganism, or manganese poisoning, she said, mimic PD in both species. She added that, in humans, “Chronic exposures to low levels of manganese may progressively extend the site of manganese deposition and toxicity to the entire area of the basal ganglia,” and that this chronic exposure can be a risk factor for PD.
Manganese-induced oxidative stress, with subsequent neuroinflammation, DNA damage, and cell apoptosis and necrosis, is a logical target for therapy by means of nutritional supplementation, said Dr. Ali.
Dr. Ali and her collaborators selected several supplements to test against both control rats fed a usual diet and those in whom manganism had been induced via a 17-day run-in period of manganese supplementation.
Wheatgrass has active constituents, including chlorophyll, vitamins, minerals, enzymes, and amino acids, and has been studied in a variety of inflammatory conditions, said Dr. Ali. Cocoa is a natural source of flavonoids and was another nutrient selected for study.
Coenzyme Q10 (CoQ10) “acts as an antioxidant that scavenges free radicals and ... protects the stability of cell membranes,” and is key to mitochondrial bioenergetics, Dr. Ali said. Finally, pomegranate contains vitamins and minerals, as well as phenolic compounds that have been studied in diabetes and Alzheimer’s disease, she said.
The study’s primary aim was to assess the neuroprotective effects of each of these four supplements singly and in combination against manganese-induced parkinsonism in rats, with a secondary aim of comparing the efficacy of each substance against the others and against the combination taken together.
The PD rats were divided into five groups, with four groups each receiving one of the supplements, and one group receiving all four in combination. The normal controls – who were dosed with saline rather than manganese – made up the sixth group of rodents studied.
After 28 days, all groups were put through a series of behavioral tests. The investigators also drew blood to assess levels of a variety of neurotransmitters, inflammatory markers, and hormones. Finally, the animals were sacrificed for histopathologic examination of the cerebral cortex, the hippocampus, and the striatum, all areas where PD-related neurodegeneration are seen.
Compared with the control rats, the manganese-dosed rats showed significantly abnormal behavior, with longer latency shown on the classic swimming test and worse working memory performance in a maze test. In most cases, though, giving a PD model rat each supplement individually resulted in significant improvements in the behavioral tests. The PD model rats given the full combination of supplements showed performance essentially equal to the control rats, Dr. Ali said. Turning to the many biochemical parameters measured in the rodent study, Dr. Ali said that the supplements all ameliorated, but did not normalize, the proinflammatory effects of manganese. Tumor necrosis factor–alpha and interleukin 1–beta levels fell by about one half with all kinds of supplementation – a significant effect – but levels still far exceeded those seen in the control rats, she said.
Dopamine and norepinephrine levels rose markedly with supplement administration as well, though serotonin levels did not. With combination therapy, both dopamine and norepinephrine values, as well as those of gamma-aminobutyric acid and glutamate, approached those of controls, said Dr. Ali.
Histology of the control rats’ brains, as expected, showed no abnormal changes in the areas examined. The manganese-dosed rats showed a variety of degenerative changes, including diffuse nuclear pyknosis, and eosinophilic plaque formation within the striatum. The brains of the rats fed the individual supplements showed essentially the same amount of degeneration. However, Dr. Ali noted, rats fed the combination therapy had brain tissue that essentially looked like that of the control rats, with “no histopathological alteration” in any area examined.
A more fine-grained examination of the data showed that overall, “Cocoa and pomegranate showed more pronounced protection against neuronal degeneration and behavioral impairments induced by manganese than wheatgrass or CoQ10,” Dr. Ali said.
Still, the combination of nutrients offered “maximum protection” against manganese-induced parkinsonism, she said. “This combination of nutrients could be a meaningful approach to reduce motor and nonmotor symptoms of Parkinson’s disease, and warrants further study in human subjects.”
Dr. Ali reported no relevant financial disclosures.