No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia

Rainer, Michael; Kraxberger, E.; Haushofer, Manfred; Mucke, Hermann Am; Jellinger, K. A.

doi:10.1007/s007020070011

Cited by 35 publications

(21 citation statements)

References 24 publications

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“…Afterwards, the safety of the stabilized orally absorbable form of NADH tablet was tested in the rat (21) and the dog (22). Rainer et al (23) reported that they found no evidence for any cognitive effect by oral NADH in dementia. NADH might also be used as a dietary supplement, but it is important to understand the fate of orally given NADH.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Metabolic Fates of Nicotinamide, NAD<sup>+</sup> and NADH Administered Orally and Intraperitoneally; Characterization of Oral NADH

Kimura

Fukuwatari

Sasaki

et al. 2006

J Nutr Sci Vitaminol

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Summary Since NADH has been implicated in medication for some symptoms and as a possible supplement for health, we characterized the metabolic fate of NADH orally given to mice by comparing with those of nicotinamide (Nam), NAD ϩ and NADH intraperitoneally or orally administered. Mice were individually housed in metabolic cages, and divided into two sets of four groups. Within each set, one group was intraperitoneally or orally administered saline and the other three groups received intraperitoneal or oral administration of a pharmacological dose of Nam, NAD ϩ or NADH (5 mol/mouse). Twenty-four hour urine samples for the day before and days 1 to 4 after administration were collected and analyzed for Nam and its metabolites. When mice were administered saline alone, urinary excretion of Nam and its metabolites, such as nicotinamide N -oxide (Nam N -oxide), N 1 -methylnicotinamide (MNA), N 1 -methyl-2-pyridone-5-carboxamide (2-Py), and N 1 -methyl-4-pyridone-3-carboxamide (4-Py), was unchanged from day 0 to day 4. Intraperitoneal injection of Nam, NAD ϩ and NADH produced significant increases in urinary excretion of Nam and its metabolites. Similar results were obtained when Nam and NAD ϩ were given orally. On the other hand, oral administration of NADH did not bring about an increase in urinary excretion of Nam and its metabolites, suggesting that NADH in digestive organs has been decomposed to a compound(s) that cannot yield Nam. In fact, incubation of NADH at acidic pH to mimic the stomach resulted in rapid conversion of NADH to an unknown compound. Better understanding of the fate of oral NADH is needed for its therapeutic and supplemental use.

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Section: Discussionmentioning

confidence: 99%

Comparison of Metabolic Fates of Nicotinamide, NAD<sup>+</sup> and NADH Administered Orally and Intraperitoneally; Characterization of Oral NADH

Kimura

Fukuwatari

Sasaki

et al. 2006

J Nutr Sci Vitaminol

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“…In a preliminary trial of NADH therapy for patients with Alzheimer's dementia, improvement was seen in cognitive function of all 17 patients tested (Birkmayer 1996). However, another study observed no cognitive improvement in patients with either AD, or vascular and frontotemporal dementia treated with NADH (Rainer et al 2000).…”

Section: Deficiency and Supplementation Of Individual Mt-nutrients Inmentioning

confidence: 94%

Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer's disease, and Parkinson's disease

Liu¹,

Ames²

2005

Nutritional Neuroscience

127

116

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Mitochondrial decay due to oxidative damage is a contributor to brain aging and age-related neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). One type of mitochondrial decay is oxidative modification of key mitochondrial enzymes. Enzyme dysfunction, that is due to poor binding of substrates and coenzymes may be ameliorated by supplementing adequate levels of substrates or coenzyme precursors. Such supplementation with mitochondrial nutrients (mt-nutrients) may be useful to prevent or delay mitochondrial decay, thus prevent or treat AD and PD. In the present review, we survey the literature to identify mt-nutrients that can (1) protect mitochondrial enzymes and/or stimulate enzyme activity by elevating levels of substrates and cofactors; (2) induce phase-2 enzymes to enhance antioxidant defenses; (3) scavenge free radicals and prevent oxidant production in mitochondria, and (4) repair mitochondrial membrane. Then, we discuss the relationships among mt-nutrient deficiency, mitochondrial decay, and cognitive dysfunction, and summarize available evidence suggesting an effect of mt-nutrient supplementation on AD and PD. It appears that greater effects might be obtained by longer-term administration of combinations of mt-nutrients. Thus, optimal doses of combinations of mt-nutrients to delay and repair mitochondrial decay could be a strategy for preventing and treating cognitive dysfunction, including AD and PD.

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“…MB has a remarkably high permeability through biomembranes, which is unparalleled by redox compounds also displaying neuroprotective properties in experimental conditions including creatine, α-lipoic acid, nicotinamide and coenzyme Q (Rainer et al, 2000; Teichert et al, 2003; Artuch et al, 2004; Lensman et al, 2006). Due to its redox nature, MB has a notable affinity for a wide variety of tissue oxidases, including those localized to mitochondria (Salaris et al, 1991; Visarius et al, 1997).…”

Section: Mechanisms Of Action Of Mb Relevant For Memory Enhancemenmentioning

confidence: 99%

Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue

Rojas

Bruchey

González-Lima

2012

Progress in Neurobiology

145

181

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This paper provides the first review of the memory-enhancing and neuroprotective metabolic mechanisms of action of methylene blue in vivo. These mechanisms have important implications as a new neurobiological approach to improve normal memory and to treat memory impairment and neurodegeneration associated with mitochondrial dysfunction. Methylene blue’s action is unique because its neurobiological effects are not determined by regular drug-receptor interactions or drug-response paradigms. Methylene blue shows a hormetic dose-response, with opposite effects at low and high doses. At low doses, methylene blue is an electron cycler in the mitochondrial electron transport chain, with unparalleled antioxidant and cell respiration-enhancing properties that affect the function of the nervous system in a versatile manner. A major role of the respiratory enzyme cytochrome oxidase on the memory-enhancing effects of methylene blue is supported by available data. The memory-enhancing effects have been associated with improvement of memory consolidation in a network-specific and use-dependent fashion. In addition, low doses of methylene blue have also been used for neuroprotection against mitochondrial dysfunction in humans and experimental models of disease. The unique auto-oxidizing property of methylene blue and its pleiotropic effects on a number of tissue oxidases explain its potent neuroprotective effects at low doses. The evidence reviewed supports a mechanistic role of low-dose methylene blue as a promising and safe intervention for improving memory and for the treatment of acute and chronic conditions characterized by increased oxidative stress, neurodegeneration and memory impairment.

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No evidence for cognitive improvement from oral nicotinamide adenine dinucleotide (NADH) in dementia

Cited by 35 publications

References 24 publications

Comparison of Metabolic Fates of Nicotinamide, NAD<sup>+</sup> and NADH Administered Orally and Intraperitoneally; Characterization of Oral NADH

Comparison of Metabolic Fates of Nicotinamide, NAD<sup>+</sup> and NADH Administered Orally and Intraperitoneally; Characterization of Oral NADH

Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer's disease, and Parkinson's disease

Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue

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