In the article on page 8, obesity and type 2 diabetes (T2D) were discussed in the con-text of fatty acid oxidation. While there is a definite need to identify natural products that could aid in the reduction of fatty acid oxidation, a variety of natural products for the improvement of diabetic neuropathy symptoms have been identified and contin-ue to be explored. Diabetic neuropathies comprise a group of heterogeneous disorders caused by poorly managed or untreated T2D. Prolonged hyperglycemia (high blood sugar levels) induces increased production of free radicals, which can damage nerve fibres and cause nerve cell death. As such,
It may well be true that if we had listened better to what our grandparents and parents taught us about the importance of eating fruit and vegetables, we would be living healthier and perhaps longer lives. Research is beginning to show us that aging, and the diseases that accompany that process, may well be the result of the decreasing ability of our bodies to deal with oxidative stress. There is also substantial evidence showing that eating adequate amounts of fruits and vegetables de-creases our chances of developing can-cer, high blood pres-sure, heart disease, stroke and diabetes.
Oxidative stress is the result of an imbalance of pro-oxidant/anti-oxidant homeostasis that leads to the overproduction of reactive oxygen species (ROS). At abnormal levels, ROS can have toxic effects including 1) damage to DNA (cancer-causing effects) or 2) damage to structural components of the brain (neurodegenerative effects, e.g. Alzheimer’s disease). A complex network of enzymes and transcriptional factors exist to counteract the effects of oxidative stress. The balance between pro-oxidant and anti-oxidant activity is weighted such that with additional stress or injury to the cell, oxidant stress leads to aging of cells, disease and damage.
nterestingly, the young broccoli sprout of about 3-4 days old is upwards of 100 times more potent as an anti-oxidant than the mature broccoli plant and most other cruciferous vegetables (cabbage, cauliflower, bok choy, and brussel sprouts). Broccoli sprouts contain a metabolite that increases the oxidant fighting capacity of the cells in our body. The anti-oxidant potential is released from the sprout when it is chewed, and the plant is broken down. A chemical in the sprout, known as glucoraphanin, combines with the enzyme myrosinase, to form the active chemical sulforaphane.
“It may well be true that if we had listened better to what our grandparents and parents taught us about the importance of eating fruit and vegetables, we would be living healthier and perhaps longer lives.”
It is sulforaphane which is the bioactive constituent of the broccoli sprout. Sulforaphane acts through a host of anti-oxidant enzymes, such as superoxide dismutase and glutathione. One of the best studied downstream effects of sulforaphane is the increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2), a protein normally sequestered (trapped) in the cytoplasm within each cell. Once released from the cell, Nrf2 enters the nucleus (control centre) of the cell and binds to a protein commonly known as antioxidant response element (ARE). ARE is the master regulator of the antioxidant system available in all human cells. By binding ARE, Nrf2 is capable of eliminating thousands, if not millions of free radicals. As such, sulfurophane acts to prevent cells from oxidative stress, slowing down the aging process and protecting cells against disease and damage. Indeed, extensive research has been completed to show the protective properties of sulforaphane in several disorders associated with oxidative stress such as cerebral ischemia, brain inflammation, and acute renal failure (1-3).
But what about newborn babies and young children? It appears that the majority of causes of injury to the newborn brain actually occur during pregnancy and late gestation (4). In many, there is an underlying, often unrecognized infection, or a reduction in blood flow from the placenta to the fetus. This can result in a build up of free radicals causing brain and other organ damage. There are a number of conditions such as cerebral palsy and other developmental disabilities in childhood (attention deficit disorder and autism spectrum disorder), which have underlying oxidative stress aetiologies due to placental insufficiency. Babies, in particular, have a lower capability of fighting free radical oxidant stress than adults do, and therefore are often more sensitive to injury.
Generally, the approach to interventions has focused on rescue therapies that will target and help recover the damaged brain tissue (5). In order for rescue therapies to be effective, they must be administered shortly after injury. Unfortunately, newborn brain injury is difficult to time and therefore treatment is complicated. As such, attention has shifted to preventing injury from occurring, and animal studies have shown promise.
The Perinatal Research Laboratory (University of Alberta), under the supervision of Dr Jerome Y Yager MD, has looked at the potential of protecting the newborn brain from injury, by supplementing the diet of pregnant rodents with broccoli sprouts. In these studies (6), pregnant rodents underwent bilateral uterine artery ligation, which mimics the placental insufficiency of cerebral palsy. The researchers have found that when supplemented with broccoli sprouts (200 mg/kg) during the last trimester of pregnancy and early infancy, newborns did not show the same developmental deficits, nor the brain injury that is often associated with children who have cerebral palsy. This was in contrast to the newborns from mothers that were not fed with broccoli spouts in their third semester of pregnancy. In other words, it appears that by enhancing the activation of Nrf2 in either the mother or the fetus, with added broccoli sprout supplementation, and presumably the activation of sulforaphane, injury to the brain, and therefore behavioural abnormalities, was prevented.
Though results in the fields of cancer, diabetes, stroke, high blood pressure and autism have also been promising regarding the use of sulforaphane and/or broccoli s p r o u t s , t h i s work stands alone in the field of the vulnerable fetus and newborn. Much work clearly needs to be done to advance this science. However, given that the majority of injury to the newborn brain occurs during pregnancy, rather than labor and delivery, work with this powerful anti-oxidant appears promising as a preventive a p p r o a c h , a n d perhaps one that may reduce the risk for developing brain damage to the millions of newborns affected around the world each year.
“The Perinatal Research Laboratory (University of Alberta)…has looked at the potential of protecting the newborn brain from injury, by supplementing the diet of pregnant rodents with broccoli sprouts.”
1. Noyan-Ashraf MH, et al. Dietary approaches to positively influence fetal determinants of adult health. FASEB J. 2006;20(2):371-3. doi: 10.1096/fj.05-4889fje.
2. Wu L, et al. Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system. PNAS. 2004;101(18):7094-9.
3. Zhao J, et al. Sulforaphane reduces infarct volume following focal cerebral ischemia in rodents. Neurosci. Lett. 2006;393(2-3):108-12.
4. Ferriero DM. Neonatal brain injury. N. Engl. J. Med. 2014;351:1985-95.
5. Nguyen A et al. Evidence for Therapeutic Intervention in the Prevention of Cerebral Palsy: Hope from Animal Model Research. Semin. Pediatr. Neurol. 2013;20:75-83.
6. Black AM et al. Broccoli sprout supplementation during pregnancy prevents brain injury in the newborn rat following placental insufficiency. Behav. Brain Res. 2015;15(291):289-98.