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The Journal of Orthomolecular Medicine Vol. 12, 2nd Quarter 1997

Neurobiology and Quantified E.E.G.

Rodolfo Marincola, M.D.

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Abstract

Brain oxidative stress may be involved in a number of diseases and aging. Coenzyme Q10 is the only known lipid soluble endogenous antioxidant that animal cells can synthesize “de novo” and for which there exist enzymatic mechanisms that can regenerate the antioxidant from its oxidized form resulting from its inhibitory effect of lipid peroxidation. Synthetic CoQ10 given to patients with benign essential hypertension has a neuropsychopharmacological effect similar to a “cognitive enhancer“ (bioequivalency concept) documented by Quantified Pharmaco EEG(QPEEG). This neuropsychopharmacological effect may play an important future role in treating or preventing cerebral oxidative damage in vascular and other conditions such as those observed in benign essential hypertension and other pathological brain conditions as well as in physiologic aging.

Introduction

Oxidative damage to the brain may be involved in aging, hypertension, stroke, Parkinson’s disease, Alzheimer’s disease, states of compromised cerebral blood flow, ionizing radiation, heavy metal intoxication, Down’s syndrome, Huntington’s disease, and other neuropsychiatric illnesses.7

In 1955 Festenstein et al In Morton’s laboratory in Liverpool observed a new compound in pig intestine, rat liver and kidney. From its chromatographic behavior, UV and IR spectra, they proposed a steroid structure, however based on its ability to be reduced and oxidized in the presence of mitochondria, succinateandcyanide,Crane et al in 1957 proposed a quinoid molecular structureas 2,3-dimethoxy5-methyl6meth-ylprenyl benzoquinone.

CoQ10 biosynthesis involves a series of steps. The first one is the synthesis of the ring from aromatic amino acids (tyrosine and phenylalanine) supplied by the diet. The other one is the synthesis of the isoprenoid side chain, followed by prenylation of the ring with the aid of 4-hydroxy-benzoate prenyltransferase. After the ring has been prenylated, there occurs a sequence of reactions involving the modifications of the ring, such as decarboxylation, hydroxylations, and methylations.

CoQ10 in the reduced form, in reconstituted membranes, in the absence of alphatocopherol, inhibited lipid peroxidation which is a conclusive evidence for its role of antioxidant in biological membranes.

Multiple experimental and clinical studies have shown the antioxidant properties of CoQ10 but its potential action over human brain function have not been reported\published.8,9

NeurotoxicityofMPTP(1-Methyl-4-phenyl-1,2,5,6,-tetrahydropyridine), produces Parkinson’s in humans and experimental animals. MPTP and Its metabolites inhibits mitochondrial respiratory chain resulting in ATP depletion in vivo which leads to secondary excitotoxicity and free radical generation, and various degrees of striatal dopamine depletion is observed. CoQ10 seems to have a protective role as documented by Shulz et al.24

CoQ10 features a high degree of hydrophobicity and its widespread occurrence in biological membranes and in low densitylipoprotein, suggest and important role in cellular defense against oxidative number of male -female, medicated only with betablockers. Excluded from the study were patients with history of hypertensive crisis, presence of any other medical conditions and hypertension treatment needing the use of diuretics.

Quantified EEG (QEEG™) and Dynamic Brain Mappingwas performed by using a Brain Function Monitoring unit #308 made by H.Z.I. Research Center, New York Medical College, with 10-20 system montages of the American E.E.G. Society, with homolateral ear electrode as reference, before and 1 hour after 100 mg. CoQ10 ( synthetic ) given orally. Digital mathematicalanalysisofthefourfrequency bands primary and first derivative cortical spontaneous bioelectrical activity recorded in the entire E.E.G. for 5 minutes in epochs of 5 seconds each.17

ANOVA of E.E.G. alpha frequencies ( 8-12 Hz ) and alpha relative power, determined that increments of less than 30% between baseline and 1 hour post CQ10 100mg. orally must be considered a placebo effect, therefore statistical significant changes are those above 30% of alpha activity, have a bioequivalent pattern of a cognitive activator (moderate psychostimulant) according with H.Z.I.

database and the International Pharmaco EEG Society. It is important to mention that with this non-invasivemethod, biodisponibility of the administered substance is determined in situ, and in a noninvasive fashion, by changes of brain cortical activity as it is shown in QEEG,therefore such substance must have been absorbed, metabolized, and eventually crossed the blood brain barrier.18,27

Quantified electrophysiology (electroencephalography and evoked potentials) refers to the computer-based acquisition, display, storage, and analysis of EEG Dynamic Brain Mappingand Topological Brain Mappingare brain function images either of frequency or time domain ( power) analysis.19 Submitted data is the average of the entire population tested.

Results

Table1 shows QEEGdata percentages of frequencies of baseline and 1 hour post CoQ10 100mg. Increments of alpha activity, are statistically significant (42%) in T values (T value= % Diffential Map(Post-Pre)ofPostMap.Itisimportant to see that this augmented alpha activity (cognitive enhancement) correlates with diminished slow activity delta and theta which is usually observed in patients with moderate to advanced cerebrovascular disease.

Figure 1(page 6) shows the transaxial view of alpha activity only, of the entire recording , (frequency domain map, real and interpolated electrodes). Decreased activity in frontal lobes, above pre Rp, and increased , below 1 hour post CoQ10. Figure 2 (page 7) shows the right lateral views, and the absolute highest map of all frequency bands (dominant activity). Note that theta activity in the frontal lobe is replaced by alpha activity in the post CoQ10 image.

Figure 3 and figure 4 (page 8) show QEEG profiles of all EEG frequency bands of test population before and after a 100 mg dose of CoQ10. The QEEG data of CoQ10 reveals a mirror-like effect of both profiles and a bioequivalent effect (a similarity to the QEEG profile of psychostimulants). Co Q10 dosing results in subjects exhibiting a slow activity Delta Theta and extremely fast Beta activity.

Figure 4 plots the Test Dose Response1HourMeanplotandthehighest similarity coefficient value for each of the recordedtimeperiods.Thegreyextensions to the X and Y axis shows the classification of the Test Dose drug where Black (center) represents no classification or a placebo effect. Conclusions

Synthetic CoQ10 given orally to patients with benign essential hypertension have a bioequivalent effect of a moderate


Neurobiology and Quantified Pharmaco E.E.G. of Coenzyme Q10

Table 1. shows QEEG Data Percentages of Frequencies of Baseline and 1 Hour Post CoQ10 100mg.

PRE ( before Rp/ ) POST ( after Rp/ )

Delta Theta Alpha Beta Delta Theta Alpha Beta

Montage R-82a

F3 9.7 32.0 26.1 32.1 4.2 18.3 34.9 47.5 F4 7.9 29.5 27.6 34.8 5.7 17.7 35.4 45.6 C3 10.0 30.2 29.1 30.5 1.1 18.0 45.5 35.1 C4 10.6 30.1 26.2 32.8 0.9 16.0 42.3 40.5 P3 11.8 30.3 32.3 25.4 1.0 13.0 51.9 33.8 P4 6.6 27.3 35.9 29.9 0.9 11.0 52.0 34.2

  1. 01 6.1 25.1 39.4 29.2 1.2 13.0 53.5 32.0

  2. 02 9.2 26.0 36.2 20.3 2.0 17.0 45.0 34.2

Montage R-82b

F7 4.3 28.9 27.6 38.9 6.4 21.2 37.5 34.6 F8 3.5 27.1 24.6 44.3 3.3 35.3 31.4 29.9 T3 3.7 27.3 29.7 39.1 2.1 15.3 46.2 36.1 T4 8.3 11.0 23.0 65.5 2.2 15.3 37.9 44.4 T5 2.2 28.4 36.5 32.7 1.6 16.6 49.0 32.5 T6 1.4 33.2 35.6 29.6 2.2 15.2 48.8 33.4

  1. 01 4.8 26.1 40.0 28.8 1.0 13.0 60.4 25.2

  2. 02 2.1 26.0 41.7 29.9 1.3 16.4 53.1 28.8

Mean of % in all leads before Rp/ Mean of % in all leads after CQ10 Alpha 31.9 45.4 Beta 34.5 34.8 Theta 27.4 17.1 Delta 5.9 2.3

Montages= topographic setting of scalp electrodes.
Increments of alpha activity, are statistically significant ( 42%) in T values ( Tvalue= %Diffential Map ( Post-
Pre ) of Post Map .

psychostimulant known as a cognitive if we think in terms of the abundance of activator/enhancer. cerebrovascular disease morbidity/mortal-

Benign hypertension is probably the ity nowadays which is frequently preceded most simple and common example of brain by a history of hypertension. Should enzyme oxidative stress and is usually associated CoQ10 be given to all patients with any form with low plasma levels of CoQ10 when of hypertension and other vascular diseases compared to normal matched controls, to prevent brain oxidative damage ? provided a model for antioxidant replace-It has been shown that post-mortem ment therapy, orthomolecular medicine, exams of brain tissue with cerebrovascular and its potential efficacy. disease have a low amount of magne-

Further research seems quite important sium (Mg), ascorbate, alpha-tocopherol,


Neurobiology and Quantified Pharmaco E.E.G. of Coenzyme Q10

40 years ago, our basic knowledge about this lipid is limited. Interest has increased recently about our only endogenous lipid-soluble antioxidant which plays an important role in the mitochondria respiratory chain as well as in most membranes.

Further research will be needed in order to establish Normal Age Related Plasma levels of CoQ10 which may be indicative of oxidative stress sustaining capacity.

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Journal of Orthomolecular Medicine Vol. 12, No. 1, 1997

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