N-acetylcysteine (NAC) : CerefolinNAC

A medical food for the dietary management of neurovascular oxidative stress and/or hyperhomocysteinemia.

N-acetylcysteine (NAC)

The effects of aging are influenced by genetic and environmental factors. Reactive oxygen species (ROS) are considered major culprits in aging and disease. ROS are byproducts of energy generation in normal metabolism and increase during infection and inflammation, exercise and stress, overexposure to sunlight and radiation, and exposure to external pollutants such as auto and diesel exhausts, emissions from power plants, cigarette smoke, pesticides, lead from old paint, and asbestos just to name a few.¹

When high levels of ROS exist with inadequate antioxidants to neutralize them, oxidative stress increases and exacerbates aging and disease. The consequences of ROS damage depends on the molecules they attack and the body's levels of antioxidants. When the target molecule is DNA, the resulting ROS-induced chemical changes lead to genetic mutations. Oxidation of lipids and proteins injures cell membranes, increases blood vessel frailty, damages immune cells and modifies enzymes.

As people age, internal antioxidant production declines. This paves the way for increased risk for disease and age-related conditions. No matter how healthy, fit or nutrition-conscious an individual has been, bombardment with environmental contaminants provokes the formation of ROS thus producing some degree of oxidative stress. This increases the demand for antioxidants at a time when the body is producing less. Glutathione levels have been shown to decrease with aging leaving neurons vulnerable to ROS attack and subsequent damage.² A steady state of oxidative stress exhausts the body's glutathione resources and outpaces its ability to replace them. Depletion of glutathione is compounded by insufficient supply of precursors for glutathione synthesis.³ As glutathione levels decrease and oxidative stress increases, the cell's ability to function progressively declines until it dies.

Boosting levels of this antioxidant powerhouse may mean taking an oral supplement. Glutathione levels cannot be increased by orally ingesting glutathione. This is because glutathione is manufactured inside the cell. The manufacture of glutathione in cells is limited by the concentration of its precursor, cysteine. Supplements that increase glutathione must provide cysteine. Glutathione levels cannot be increased by ingesting oral cysteine because oral cysteine is potentially toxic and is spontaneously destroyed in the gastrointestinal tract.

N-acetylcysteine is the bioavailable form of cysteine and dramatically increases the body's production of glutathione, the brain's most important scavenger of free radicals.

CEREFOLIN^®NAC HELPS PROTECT THE HEALTH OF NEURONS

(Data on file)

This graph represents technical information presented in: Ho P, Collins S, Dhitavat S, Ortiz D, Ashline D, Rogers E, Shea T. Homocysteine potentiates ß-amyloid neurotoxicity: role of oxidative stress. Journal of Neurochemistry. 2001;78:249-253.

DUAL ACTION OF N-ACETYLCYSTEINE

Homocysteine Reduction
N-acetylcysteine is effective in homocysteine reduction. Evidence indicates that N-acetylcysteine alone can reduce elevated homocysteine levels by 20-50%. ^{4 5}

Antioxidant
N-acetylcysteine's effectiveness is primarily attributed to its ability to stimulate the synthesis of glutathione. In an in vivo study⁶, researchers investigated the effects of N-acetylcysteine on glutathione levels in the brains of mice. They compared a control group that was not given N-acetylcysteine to a group that was injected with N-acetylcysteine. Nerve cell samples were examined from both groups. Neurons from the N-acetylcysteine treated group had significantly higher levels of total glutathione compared to controls. (P<0.01)

Glutathione Level After Treatment with NAC

This graph represents technical information presented in: Pocernich C et al. In-vivo glutathione elevation against hydroxyl free radical-induced protein oxidation in rat brain. Neurochemistry International 2000;36:185-191.

NAC REDUCES FREE RADICAL ATTACKS ON PROTEIN

Free radical attacks on protein produce protein peroxidation. Protein peroxidation is increased in AD brains and linked to oxidative stress. Glutathione has been shown to reduce formation of free radicals that attack proteins causing peroxidation.

In the previous in vivo study ⁷ both the control and N-acetylcysteine (NAC) groups were exposed to iron (Fe) and hydrogen peroxide (H₂O₂) which are known to cause protein peroxidation. To examine the effect of NAC, nerve cells were obtained from both groups. The NAC group that previously demonstrated elevations in glutathione was found to be better protected against protein peroxidation. The NAC group had less evidence of protein damage than the control group. From this study, it is most likely that the protective effects of NAC resulted from an NAC-induced increase in glutathione levels. (p<0.01)

NAC Reduces Protein Oxidation in Neurons Exposed to Hydrogen Peroxide (H₂O₂)

This graph represents technical information presented in: Pocernich C et al. In-vivo glutathione elevation against hydroxyl free radical-induced protein oxidation in rat brain. Neurochemistry International 2000;36:185-191.

GLUTATHIONE REDUCES FREE RADICAL ATTACKS ON DNA

Beta amyloid plaque (Aß) has been shown to induce oxidative stress. Many studies have shown that Aß causes excessive calcium influx into neurons which results in excitotoxicity. Overexcited neurons generate ROS (free radicals) and contribute to neurotoxic death.

In a recent (2005) in vivo study, the protective role of glutathione against the oxidative and neurotoxic effects of Aß was evaluated. Not surprisingly, the authors found protein peroxidation and neurotoxicity increased in neurons treated with Aß. When the glutathione level in Aß treated neurons increased, protein peroxidation and excitotoxicity decreased.⁸

These results show that the up-regulation of glutathione protects nerve cells from oxidative stress and neurotoxicity caused by Aß. Nerve cell death is associated with progressive memory loss.

Another significant finding of this study was the neurons exposed to Aß showed extensive DNA damage and nerve cell death. When neurons were pre-treated to increase glutathione levels, there was a significant reduction in DNA damage and neuronal death when exposed to Aß (p<0.05)

NAC REDUCES DNA DAMAGE IN NEURONS

This graph represents technical information presented in: Boyd-Kimball D et al. Gamma-Glutamylcysteine ethyl ester-induced up-regulation of glutathione protects neurons against Aß (1-42)-mediated oxidative stress and neurotoxicity: implications for Alzheimer's disease. Journal of Neuroscience Research 2005;79:700-706.

Cerefolin^®NAC contains N-acetylcysteine which increases levels of GSH. GSH played a protective role in the oxidative and neurotoxic damage induced by Aß.

References

1. Monograph: Glutathione, Reduced (GSH). Alternative Medicine Review 2001;6(6):601-607.
2. Lui R and Choi J. Age-associated decline in Gamma-glutamylcysteine synthetase gene expression in rats. Free Radical Biology Medicine 2000;28:566-574.
3. Pocernich C et al. In-vivo glutathione elevation against hydroxyl free radical-induced protein oxidation in rat brain. Neurochemistry International 2000;36:185-191.
4. Ibid.
5. Hultberg B et al. Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine. Scandinavian Journal of Clinincal Laboratory Investigation 1994;54(6):417-22.
6. Pocernich.
7. Ibid.
8. Boyd-Kimball D et al. Gamma-Glutamylcysteine ethyl ester-induced up-regulation of glutathione protects neurons against Aß (1-42)-mediated oxidative stress and neurotoxicity: implications for Alzheimer's disease. Journal of Neuroscience Research 2005;79:700-706.

Cerefolin®NAC is a medical food for the dietary management of neurovascular oxidative stress and/or hyperhomocysteinemia. CerefolinNAC.com © 2007