NAD Abstracts 2

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The Coenzyme Nicotinamide Adenine Dinucleotide (NADH) As Biological Antidepressive Agent

            (Birkmayer 1991) Download

The coenzyme nicotinamide adenine dinucleotide (NADH) has been used in an open label trial as medication in 205 patients suffering from depression with various clinical symptoms. NADH was given orally, intramuscularly or intravenously. The duration of therapy ranged from 5 to 310 days. 93% of the patients exhibited a beneficial clinical effect. An improvement up to 44 with a mean value of 11,5 was observed.

Nicotinamide adenine dinucleotide (NADH)--a new therapeutic approach to Parkinson's disease. Comparison of oral and parenteral application

            (Birkmayer, Vrecko et al. 1993) Download

The reduced coenzyme nicotinamide adenine dinucleotide (NADH) has been used as medication in 885 parkinsonian patients in an open label trial. About half of the patients received NADH by intravenous infusion, the other part orally by capsules. In about 80% of the patients a beneficial clinical effect was observed: 19.3% of the patients showed a very good (30-50%) improvement of disability, 58.8% a moderate (10-30%) improvement. 21.8% did not respond to NADH. Statistical analysis of the improvement in correlation with the disability prior to treatment, the duration of the disease and the age of the patients revealed the following results: All these 3 parameters have a significant although weak influence on the improvement. The disability before the treatment has a positive regression coefficient (t value < 0.01). The duration of the disease has a negative regression coefficient (< 0.01) and so has the age a negative regression coefficient (t value < 0.05). In other words younger patients and patients with a shorter duration of disease have a better chance to gain a marked improvement than older patients and patients with longer duration of the disease. The orally applied form of NADH yielded an overall improvement in the disability which was comparable to that of the parenterally applied form.

Patent NADH and NADPH therapeutic agents for nasal, sublingual, rectal and dermal administration

Birkmayer 1996 Download

NADH in Cancer Prevention and Therapy

            Birkmayer 2005 Download

The role of NADH in Cancer Therapy

            Birkmayer 2007 Download

NADH (Coenzyme 1) Newest findings

            Birkmayer 2011 Download

Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR)

            (Bushehri, Jarrell et al. 1998) Download

A gradual increase in blood pressure (BP), often attaining hypertensive levels, is common during aging--"age-related hypertension." Therefore, means to prevent or ameliorate this elevated BP safely are important. Although oral B-nicotinamide adenine dinucleotide (NADH), a natural coenzyme, is used principally to treat various neurologic disorders, we wished to investigate whether this agent had the same potential to lower BP and benefit the cardiovascular system as does coenzyme Q10, a similar-type agent. As a first approximation, spontaneously hypertensive rats (SHR) were used to determine effects of oral NADH. In a blinded, placebo-controlled study, ten rats received placebo; and ten, NADH for ten weeks. Systolic BP was measured by tail plethysmography. Blood was collected terminally, and chemistries were performed by routine methodologies. Thiobarbituric acid reactive species (TBARS) (an estimate of lipid peroxidation/free radical formation) was measured in renal and hepatic tissues. The following was noted: water and food intake were comparable, and the steady weight gain of young SHR were similar in the placebo and NADH groups. Although systolic BP did not differ between the two groups over the first month, it decreased and stayed markedly lower for the remainder of study in SHR receiving oral NADH. At the end of 60 days, SBP in NADH-treated SHR was 184 mm Hg +/- 2.8 (SEM) compared to 201 mm Hg +/- 2.1 (SEM) in control SHR (p < 0.001). No significant differences were seen in blood levels of glucose, insulin, triglyceride, and HDL levels but NADH intake lowered total cholesterol (p < 0.002) and LDL (p < 0.02). Renal TBARS were also significantly lower in SHR receiving NADH (P < 0.001). Accordingly, supplementation with the natural coenzyme NADH theoretically could prove to be useful in preventing age-related increases in BP and, thus, various cardiovascular maladies.

Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study

            (Demarin, Podobnik et al. 2004) Download

This study was designed to evaluate the effect of stabilized oral reduced nicotinamide adenine dinucleotide (NADH) on cognitive functioning in patients with Alzheimer's disease (AD). NADH is a coenzyme that plays a key role in cellular energy production and stimulates dopamine production. In previous trials NADH has been shown to improve cognitive functioning in patients with Parkinson's disease, depression and AD. The present trial was a randomized, placebo-controlled, matched-pairs, double-blind, 6-month clinical study. Patients with probable AD (n = 26) were randomized to receive either stabilized oral NADH (10 mg/day) or placebo. Twelve pairs of subjects were matched for age and baseline total score on the Mattis Dementia Rating Scale (MDRS) and the Mini Mental State Examination. After 6 months of treatment, subjects treated with NADH showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05). Analysis of MDRS subscales revealed significantly better performance by NADH subjects on measures of verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and a trend (p = 0.08) to better performance on a measure of abstract verbal reasoning. There were no differences between groups in measures of attention, memory, or in clinician ratings of dementia severity (Clinical Dementia Rating). Consistent with earlier studies, the present findings support NADH as a treatment for AD.

Biomarkers in Alzheimer's disease

            (Demarin, Zavoreo et al. 2011) Download

Dementia is a growing public health concern because of the lack of effective curative treatment options and a rising global prevalence. Alzheimer's disease (AD) is the most common type of dementia, affecting 60%-70% of all patients with dementia. The main pathological features of Alzheimer's dementia are neurofibrillary tangles and senile plaques caused by progressive deposition of beta-amyloid in the brain, but its underlying pathological basis is unclear. In common late onset AD sporadic forms (95% of all AD cases), a major genetic risk factor is the apolipoproteinE-varepsilon4 (ApoE-varepsilon4) alleles, and other genetic determinants have also been proposed to play causative role. This review focuses on biomarkers and subsequent changes in continuous measurement of cognitive and functional abilities in patients with mild cognitive impairment (MCI) and AD that aim to achieve a higher diagnostic accuracy for AD along with clinical assessment, neuropsychological testing and neuroimaging.

NADH - neue Wege in der Behandlung des klimakterischen Syndroms

            Friedrich 2006 Download

NADH: sensor of blood flow need in brain, muscle, and other tissues

            (Ido, Chang et al. 2001) Download

NADH augments blood flow in physiologically activated retina and visual cortex

            (Ido, Chang et al. 2004) Download

The mechanism(s) that increase retinal and visual cortex blood flows in response to visual stimulation are poorly understood. We tested the hypothesis that increased transfer of electrons and protons from glucose to cytosolic free NAD(+), reducing it to NADH, evoked by increased energy metabolism, fuels redox-signaling pathways that augment flow. The near-equilibrium between free cytosolic NADH/NAD(+) and lactate/pyruvate ratios established by lactate dehydrogenase predicts that transfer of additional electrons and protons from injected lactate to NAD(+) will augment the elevated blood flows in stimulated retina and cortex, whereas transfer of electrons and protons from NADH to injected pyruvate will attenuate the elevated flows. These predictions were tested and confirmed in rats. Increased flows evoked by stimulation also were prevented by inhibition of nitric oxide synthase. These findings support an important role for cytosolic free NADH in fueling a signaling cascade that increases *NO production, which augments blood flow in photostimulated retina and visual cortex.

Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease

            (Kapogiannis and Mattson 2011) Download

Epidemiological, neuropathological, and functional neuroimaging evidence implicates global and regional disruptions in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified by excitatory and inhibitory synaptic activity and neurotrophic factors. Ageing and Alzheimer's disease cause perturbations in cellular energy metabolism, level of excitation or inhibition, and neurotrophic factor release, which overwhelm compensatory mechanisms and result in dysfunction of neuronal microcircuits and brain networks. A prolonged positive energy balance impairs the ability of neurons to adapt to oxidative and metabolic stress. Results from experimental studies in animals show how disruptions caused by chronic positive energy balance, such as diabetes, lead to accelerated cognitive ageing and Alzheimer's disease. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signalling) have been effective in animal models and in preliminary studies in humans.

NADH monograph

         Kelley 2006 Download

X-ray induced L02 cells damage rescued by new anti-oxidant NADH

            (Liu and Zhang 2003) Download

AIM: To explore molecular mechanism of nicotinamide adenine dinucleotide (NADH) antagonization against X-ray induced L02 cells damage. METHODS: L02 liver cells were cultured in RPMI 1640, exposed to X-ray irradiation and continued to culture in the presence or absence of NADH. Cellular viability was analyzed by routine MTT methods. The percent age of apoptotic cells and positive expressions of p53, bax and bcl-2, fas, fasL proteins were determined by FCM. Level of intracellular ROS was determined by confocal microscope scanning. Morphological change was detected by scanning electron micrograph. RESULTS: The viability of L02 cells was decreased with increasing dose of X-ray irradiation. NADH could not only eliminate the apoptosis induced by X-ray irradiation, but also up-regulate expression of bcl-2 protein and down-regulate expression of p53, bax, fas and fasL proteins (P<0.05). At the same time, NADH could reduce level of intracellular ROS in radiated L02 cells. CONCLUSION: NADH has marked anti-radiation effect, its mechanism may be associated with up-regulation of bcl-2 expression and down-regulation of p53, bax fas and fasL expression, as well as decline of intracellular ROS. However, further investigation of its mechanism is worthwhile.

The vitamin nicotinamide: translating nutrition into clinical care

            (Maiese, Chong et al. 2009) Download

Nicotinamide, the amide form of vitamin B(3) (niacin), is changed to its mononucleotide compound with the enzyme nicotinic acide/nicotinamide adenylyltransferase, and participates in the cellular energy metabolism that directly impacts normal physiology. However, nicotinamide also influences oxidative stress and modulates multiple pathways tied to both cellular survival and death. During disorders that include immune system dysfunction, diabetes, and aging-related diseases, nicotinamide is a robust cytoprotectant that blocks cellular inflammatory cell activation, early apoptotic phosphatidylserine exposure, and late nuclear DNA degradation. Nicotinamide relies upon unique cellular pathways that involve forkhead transcription factors, sirtuins, protein kinase B (Akt), Bad, caspases, and poly (ADP-ribose) polymerase that may offer a fine line with determining cellular longevity, cell survival, and unwanted cancer progression. If one is cognizant of the these considerations, it becomes evident that nicotinamide holds great potential for multiple disease entities, but the development of new therapeutic strategies rests heavily upon the elucidation of the novel cellular pathways that nicotinamide closely governs.

Chronic fatigue syndrome and mitochondrial dysfunction

         (Myhill, Booth et al. 2009) Download

This study aims to improve the health of patients suffering from chronic fatigue syndrome (CFS) by interventions based on the biochemistry of the illness, specifically the function of mitochondria in producing ATP (adenosine triphosphate), the energy currency for all body functions, and recycling ADP (adenosine diphosphate) to replenish the ATP supply as needed. Patients attending a private medical practice specializing in CFS were diagnosed using the Centers for Disease Control criteria. In consultation with each patient, an integer on the Bell Ability Scale was assigned, and a blood sample was taken for the "ATP profile" test, designed for CFS and other fatigue conditions. Each test produced 5 numerical factors which describe the availability of ATP in neutrophils, the fraction complexed with magnesium, the efficiency of oxidative phosphorylation, and the transfer efficiencies of ADP into the mitochondria and ATP into the cytosol where the energy is used. With the consent of each of 71 patients and 53 normal, healthy controls the 5 factors have been collated and compared with the Bell Ability Scale. The individual numerical factors show that patients have different combinations of biochemical lesions. When the factors are combined, a remarkable correlation is observed between the degree of mitochondrial dysfunction and the severity of illness (P<0.001). Only 1 of the 71 patients overlaps the normal region. The "ATP profile" test is a powerful diagnostic tool and can differentiate patients who have fatigue and other symptoms as a result of energy wastage by stress and psychological factors from those who have insufficient energy due to cellular respiration dysfunction. The individual factors indicate which remedial actions, in the form of dietary supplements, drugs and detoxification, are most likely to be of benefit, and what further tests should be carried out.

The Reduced Coenzyme Nicotnamide Adenine Dlnuclcotide (NADH) Prevents Hepatic Cells From Apoptosis by Mitochondria-dependant Signaling Pathway

         (Xu and Zhang 2000) Download

Birkmayer, G. D. (1991). "The Coenzyme Nicotinamide Adenine Dinucleotide (NADH) As Biological Antidepressive Agent." New Trends in Clinical Neuropharmacology V(314).

Birkmayer, J. G., C. Vrecko, et al. (1993). "Nicotinamide adenine dinucleotide (NADH)--a new therapeutic approach to Parkinson's disease. Comparison of oral and parenteral application." Acta Neurol Scand Suppl 146: 32-5.

Bushehri, N., S. T. Jarrell, et al. (1998). "Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR)." Geriatr Nephrol Urol 8(2): 95-100.

Demarin, V., S. S. Podobnik, et al. (2004). "Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study." Drugs Exp Clin Res 30(1): 27-33.

Demarin, V., I. Zavoreo, et al. (2011). "Biomarkers in Alzheimer's disease." Clin Chem Lab Med 49(5): 773-8.

Ido, Y., K. Chang, et al. (2004). "NADH augments blood flow in physiologically activated retina and visual cortex." Proc Natl Acad Sci U S A 101(2): 653-8.

Ido, Y., K. Chang, et al. (2001). "NADH: sensor of blood flow need in brain, muscle, and other tissues." FASEB J 15(8): 1419-21.

Kapogiannis, D. and M. P. Mattson (2011). "Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease." Lancet Neurol 10(2): 187-98.

Liu, F. Q. and J. R. Zhang (2003). "X-ray induced L02 cells damage rescued by new anti-oxidant NADH." World J Gastroenterol 9(8): 1781-5.

Maiese, K., Z. Z. Chong, et al. (2009). "The vitamin nicotinamide: translating nutrition into clinical care." Molecules 14(9): 3446-85.

Myhill, S., N. E. Booth, et al. (2009). "Chronic fatigue syndrome and mitochondrial dysfunction." Int J Clin Exp Med 2(1): 1-16.

Xu, M. and J. Zhang (2000). "The Reduced Coenzyme Nicotnamide Adenine Dlnuclcotide (NADH) Prevents Hepatic Cells From Apoptosis by Mitochondria-dependant Signaling Pathway." Int J Molecular Cancer Therapy 3(1).