What is Oleuropein?

The Mediterranean diet (MD) is claimed to prevent age-related dysfunctions, including neurodegeneration, possibly due to its richness in plant polyphenols, considered active against aging- and disease-related neurodegeneration with mechanisms still to be completely deciphered. Polyphenols are natural plant secondary metabolites which exhibit remarkable multipotent ability to control and modulate ROS, metal toxicity, inflammation, apoptosis, signal transduction, ion channels, and neurotransmitters(1). Oleuropein and its aglycone are the major polyphenols in the leaves and drupes of Oleaceae, particularly Olea Europaea, yet with different abundancies in the various cultivars, and in the extra virgin olive oil (EVOO) thereof(2). Together with resveratrol and other plant polyphenols, olive polyphenols, including hydroxytyrosol (HT) and oleocanthal, are typical components of the MD. Available reports suggest that a close adherence to the MD enhances cognitive function, reduces the risk of developing mild cognitive impairment and of conversion of the latter to AD (3). Studies in rodents suggest that diet supplementation with phenol-rich components of the MD such as red wine and EVOO improves several pathological conditions, with particular emphasis on aging- and disease-associated cognitive and behavioral deficits.

What is Bioavaible Glutathione?

GSH is the most abundant non-protein thiol in mammalian cells and the preferred substrate for several enzymes in xenobiotic metabolism and antioxidant defense. It plays an important role in many cellular processes, such as cell differentiation, proliferation, apoptosis, in metal transport, storage and metabolism, and is involved in the process of conjugation of metals through production of complexes via non-enzymatic reactions. GSH functions as a source of cysteine for metal binding, and as a reductant or cofactor in redox reactions involving metals. The sulfhydryl group of the cysteine moiety of GSH has a high affinity for metals such as mercury, silver, cadmium, lead, zinc and copper, forming a thermodynamically stable complex that can be eliminated.

What is the purpose of the vitamins present in the product?

Preservation of cognitive ability well in old age is essential not only to promote an adequate health status but also to delay the onset of dementia and slow down its progress. As a curative treatment is currently not possible for dementia, a number of attempts have been made to find out the non genetic risk factors that may be modified to limit it. Vitamins B12, B6, D3 and E are well known essential substances whose deficiency in elderly is described to increase the risk of neurodegenerative processes occurrence. Many studies reported an association between antioxidant nutrients, such as vitamins E, carotenoids and flavonoids and a lower risk of cognitive decline or AD, but few studies have investigated this association in relation to vitamin supplements. Observational studies found that the use of vitamin E supplements was inversely associated with subsequent risk of cognitive decline or but not consistently. The biological plausibility of a beneficial effect of antioxidant vitamins on cognitive function has been supported by the endogenous capacity of these compounds to reduce neuronal damage and death caused by oxidative stress, which contributes to the pathogenesis of dementia. Some research showed that pathological AD changes are already well established in the brain in a substantial fraction of people diagnosed with cognitive impairment. In addition, low blood levels of vitamins E and C are associated with a memory deficit in older dementia-free persons(4). Particularly, Vitamin E bioavailability, metabolism and plasma levels have been studied in humans and in AD, particularly as α-tocopherol. Vitamin E has been shown to cross the blood brain barrier and to accumulate at therapeutic levels in the central nervous system, where it is able to lower lipid peroxidation and β-amyloid deposition. It also rescues neuronal damage and β-amyloid deposition in the brain by reducing isoprostane levels.

What are Antioxidants?

The free radical and oxidative stress theory of aging suggests that oxidative damage is a major player in neuronal degeneration and several studies have demonstrated that oxidative stress is an early occurring condition in AD. Antioxidants are a group of endogenous or exogenous molecules that “when present in low concentrations compared to that of an oxidizable substrate, significantly delays or inhibits the oxidation of that substrate”. Antioxidants act at the level of removing and scavenging ROS and ROS precursors, inhibiting ROS and other free radical formation and binding metal ions necessary for the catalysis of ROS generation.

The natural antioxidant system can be subdivided in enzymatic and non-enzymatic antioxidants. As opposed to chelating agents, that are indirect antioxidants, the direct antioxidants are scavenging and chain-breaking molecules represented mainly by the exogenous ascorbate (vitamin C), tocopherols/ tocotrienols (vitamin E) and carotenoids. Endogenous direct antioxidants include molecules such as glutathione, uric acid and bilirubin. Reliable publications have determined that reduced glutathione (GSH) protects cultured neurons against oxidative damage resulting from β-peptide and 4-hydroxynonenal (HNE), a lipid peroxidation product that is increased in AD. GSH, in fact, protects the affected areas through the formation of metal complexes via non-enzymatic reactions and may also be beneficial in normalizing the adverse effects of iron accumulation in the aging brain (6). Up to now use of antioxidants in prevention or therapy gave conflicting results. One possible explanation is related to the low permeability of the blood brain barrier to most of the antioxidants currently used. An important topic is the still unknown fine tuned equilibrium among different antioxidants and free radical production. It is conceivable that the use of multiple antioxidants, supported by measurements of biomarkers reflecting the antioxidant status of patients, can lead to more positive results (5).

*These statements have not been evaluated by Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent disease.

1. Khushwant S., et al., Polyphenols: Multipotent Therapeutic Agents in Neurodegenerative Diseases. Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada. 10 March 2013; Accepted 29 April 2013.
2. Casamenti F, et. al., Oleuropein Aglycone: A Possible Drug against Degenerative Conditions. In Vivo Evidence of its Effectiveness against Alzheimer’s Disease. J Alzheimers Dis. 2015 Jan 1;45(3):679-88.
3. Casamenti F, Stefani M. Olive polyphenols: new promising agents to combat aging-associated neurodegeneration. Expert Rev Neurother. 2016 Oct 20:1-14.
4. Basambombo LL, et al., Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline. Ann Pharmacother. 2017 Feb;51(2):118-124.
5. Mecocci P, Polidori MC. Antioxidant clinical trials in mild cognitive impairment and Alzheimer’s disease. Biochim Biophys Acta. 2012 May;1822(5):631-8.
6. Cacciatore I, et al., Prodrug approach for increasing cellular glutathione levels. Molecules. 2010 Mar. 3;15(3):124