Natural Supplements to Ward Off Alzheimer’s (Aging on the Brain: The Neurodegenerative Battle)

Alpha-glyceryl phosphoryl choline (alpha GPC) is a precursor for the synthesis of phosphatidylcholine, which may help stimulate human growth hormone (HGH) release. In a study published in the International Journal of Clinical Pharmacology 12 normal volunteers were studied on three randomized occasions: in a control day without drug administration, after 1,000 mg of intramuscular (IM) alpha GPC (as AlphaSize™, from Chemi Nutra), and after 1,000 mg of IM citicoline, respectively.¹¹ Alpha GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of citicoline, plasma choline levels showed a similar time course, but were considerably lower than those observed after alpha GPC. Pharmacokinetic parameters calculated after subtracting the zero time concentration from all post-drug values indicated that exogenously derived choline declined in plasma with a half-life of 0.5 to 6.2 hour, without any significant difference between alpha GPC or citicoline. Choline AUC values after alpha GPC were significantly higher than those observed after citicoline, but the difference was no longer significant when AUC’s were corrected for the different choline content of the two preparations. Researchers concluded that the IM administration of alpha GPC provides an effective means of increasing plasma choline levels.

A Japanese in vivo study examined the neurotoxic effect of A beta and the neuroprotective effect of phosphatidylinositol using transgenic mice.¹² Intrahippocampal CA1 injection of 1.5 mul of 100 nM or 1 microM A beta25-35 increased the number of degenerating neurons in one month, demonstrating an in vivo neurotoxic effect of A beta at lower concentrations after diffusion. Intrahippocampal co-injection or intracerebroventricular administration of 1.5 microl of 500 nM phosphatidylinositol prevented the A beta25-35-induced neuronal degeneration in all the hippocampal regions, while co-injection of another acidic phospholipid, phosphatidylserine (1.5 microl, 500 nM) with A beta25-35 showed no protective effects.

In contrast, studies have shown the positive effects of phosphatidylserine, a phospholipid essential for the normal functioning of neuronal cell membranes, which is mainly found in fish, green leafy vegetables, soybeans and rice.

A double blind Italian study treated 494 elderly patients with moderate to severe cognitive decline with 300 mg/d of bovine cortex-derived phosphatidylserine for six months.¹³ Within the six-month trial period, 69 patients dropped out. Compared to the placebo group, statistically significant improvements in behavioral and cognitive parameters in the phosphatidylserine-treated group were observed. In addition, clinical evaluation and laboratory tests demonstrated that the phosphatidylserine was well tolerated.

Researchers at the University of Munich, Germany, gave 33 patients with mild primary degenerative dementia either 300 mg of bovine-derived phosphatidylserine (from Fidia) or a placebo.¹⁴ Both treatment phases lasted for eight weeks with an eight-week washout phase in between and a four-week washout phase before treatment phase one. The phosphatidylserine treated patients showed significantly more improvement in clinical global improvement ratings than the placebo during treatment phase one. The improvement carried over to the following washout and treatment phases. There were no significant improvements in GBS dementia rating scale, psychometric tests or P300-latency. The patients initially showed higher power values in all frequency bands except alpha, when compared to a younger, healthy control group. Phosphatidylserine reduced the higher power values compared to the placebo, shifting electroencephalographic (EEG) power more toward the normal level.

An open, uncontrolled study published in Clinical Trials Journal involved 27 patients with senile cognitive decline given 300 mg/d of phosphatidylserine for 60 days.¹⁵ A series of neuropsychological tests and the Geriatric Rating Scale were used. During the treatment period, an improvement in cognitive and behavioral functions was observed; the improvement persisted for a month after the end of therapy.

Vinpocetine, a semi-synthetic derivative alkaloid of vincamine, an extract from periwinkle, has been found to increase blood flow and glucose metabolism. A randomized, double blind crossover study at the University of Leeds, Leeds, UK, gave 12 healthy female volunteers pre-treatments with vinpocetine (as BioVinca™, from Cyvex) 10, 20, 40 mg and placebo for two days.¹⁶ On the third day of treatment and one hour following the morning dosage, the subjects completed several psychological tests. There was no significant change in the placebo group on the critical flicker fusion, choice reaction time or subjective ratings of drug effects; however, memory was significantly improved after treatment with 40 mg of vinpocetine when compared to placebo. The results suggest a localized effect of the drug on the serial comparison stage of the reaction process.

Another botanical derived from the root of Angelica gigas Nakai has shown positive effects on memory. A Korean 12-week clinical trial examined the effects of INM 176 (as Cogni-Q, from Maypro) compared with a placebo on the cognitive functions of 92-year-old subjects with cognitive impairment.¹⁷ The subjects scored less than 25 points on the Korean Mini Mental Status Exam (K-MMSE) and showed a high risk of Alzheimer’s from the Neurocognitive Screening Battery. The INM 176 group’s total error score in the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog) decreased significantly (P<0.01), whereas the placebo group showed a slight increase. The mean changes in Instrumental Activities of Daily Living (IADL) and Geriatric Depression Scale (GDS), from baseline scores, favored the INM 176 group more than in the placebo group and outcome changes of ADAS-cog, IADL, KGDS scores during the 12 week clinical trial showed favorable responses in the INM 176 administered group; however, further clinical trials are needed to demonstrate its efficacy. An in vivo study at Seoul National University administered decursin, a major coumarin constituent isolated from Angelica gigas, to mice at 1 and 5 mg/kg body weight with scopolamine-induced amnesia.¹⁸ The decursin significantly ameliorated scopolamine-induced amnesia, measured in the passive avoidance test and the Morris water maze test. Decursin also significantly inhibited acetylcholinesterase (AChE) activity by 34 percent in the hippocampus of the treated mice.

Another study allowed mice free access to drinking water (control group) or water containing different concentrates of an ethanolic extract of Angelica gigas Nakai (EAG).¹⁹ After four weeks, A beta1-42 was injected intracerebroventricular. The mice previously treated with EAG (0.1 percent) significantly blocked the A beta1-42-induced impairment in passive avoidance performance. Next, mice were fed chow mixed with various doses of decursinol for four weeks, before A beta1-42 was injected. The mice pretreated with decursinol (0.001 percent, 0.002 percent and 0.004 percent) significantly attenuated the A beta1-42-induced impairment in passive avoidance performance. Decursinol (0.004 percent) also significantly blunted the A beta1-42-induced decrease in alternation behavior in the Y-maze test without change in general locomotor activity.

Further, a study published in the Journal of Natural Products showed decursinol represented the highest inhibitory activity toward AChE in vitro, out of 11 known isolated coumarins.²⁰

Antioxidants are a weapon beneficial for fighting off oxidation that may cause cell death. A study at the University of Washington, Seattle, gave mouse pups access to drinking water with pomegranate juice, at one of three doses, as well as plain water, sugar water and vitamin C water controls during the last third of pregnancy and throughout the duration of litter suckling.²¹ At postnatal, day seven, the pups underwent unilateral carotid ligation followed by exposure to 8 percent oxygen for 45 minutes. Dietary supplementation with pomegranate juice resulted in markedly decreased brain tissue loss (>60 percent) in all three brain regions assessed, with the highest pomegranate juice dose having the greatest significance (P< or = 0.0001). Pomegranate juice also diminished caspase-3 activation by 84 percent in the hippocampus and 64 percent in the cortex. Ellagic acid, a polyphenolic component in pomegranate juice, was detected in plasma from treated but not control pups.