Reassessing the role of NAD as a prosurvival factor

Preyat, Nicolas; Léo, Oberdan

doi:10.1080/23723556.2015.1062591

Cited by 3 publications

(3 citation statements)

References 10 publications

(10 reference statements)

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“…Nicotinamide adenine dinucleotide has 3 related precursor vitamins – nicotinamide, nicotinic acid, and nicotinamide riboside – that have highly efficient synthetic and recycling ‘salvage’ pathways and one ‘detoxification’ pathway using nicotinamide N -methyltransferase (NNMT). 48–54 There is an important backup nicotinamide/NAD ‘de novo’ synthetic pathway from the essential amino acid tryptophan. 55 This pathway is crucial to our story as it is closely linked with immunologic tolerance and intolerance.…”

Section: Biochemical Backgroundmentioning

confidence: 99%

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Hill

Williams

2017

Int J�Tryptophan�Res

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Meat and vitamin B3 – nicotinamide – intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by ‘welcoming’ gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B3 deficiency may now be common among the poor billions on a low-meat diet. Disease transitions to non-communicable inflammatory disorders (but longer lives) may be driven by positive ‘meat transitions’. High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B3 could lead to better health, but such a preventive approach needs more equitable meat distribution. Some people may require personalised doses depending on genetic make-up or, temporarily, when under stress.

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Section: Biochemical Backgroundmentioning

confidence: 99%

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Hill

Williams

2017

Int J�Tryptophan�Res

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“…The change of the NAD + level in a cell may not only affect apoptosis but also other types of cell death, such as necroptosis [50,51], autophagy [52,53], and parthanatos [54,55]. As NAD + and NADH play crucial roles in a number of fundamental biological processes, such as energy metabolism, mitochondrial functions, and gene regulation, the fluctuation in the intracellular NAD+ pool may serve as a potential therapeutic target for treating several disorders.…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide phosphoribosyltransferase aggravates inflammation and promotes atherosclerosis in ApoE knockout mice

Kong

Zhang

et al. 2019

Acta Pharmacol Sin

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Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme of nicotinamide adenine dinucleotide (NAD) salvage biosynthesis in mammals, and is involved in fundamental physiological processes and pathophysiology of many diseases. Thus far, however, the role of Nampt in atherosclerosis development is still in debate. In this study, we crossed global Nampt transgenic mice (Nampt-Tg) with a well-established atherosclerosis animal model (ApoE knockout mice, ApoE −/−) to generate ApoE −/− ;Nampt-Tg mice and investigated the effects of Nampt overexpression on atherosclerosis development in ApoE −/− mice. Both ApoE −/− and ApoE −/− ;Nampt-Tg mice were fed with a pro-atherosclerotic high-fat diet (HFD) for 16 weeks. Their serum lipid contents and atherosclerotic lesion were assessed. The results showed that there was no significant difference in body weight or serum levels of glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol between the two strains of mice, but ApoE −/− ;Nampt-Tg mice had a significantly higher level of serum non-esterified fatty acid. Compared with ApoE −/− mice, ApoE −/− ;Nampt-Tg mice displayed significantly increased atherosclerotic lesion area and thickness, lower collagen content, decreased collagen I/III ratio (collagen immaturation), increased number of apoptotic cells, and enhanced activities of caspase-3, caspase-8, and caspase-9. Moreover, macrophage infiltration (F4/80 staining), tumor necrosis factor signaling, and chemokines expression (ICAM-1 and CXCR-4) were all activated in aortic atherosclerotic plaque of ApoE −/− ;Nampt-Tg mice compared with ApoE −/− mice. Our results provide in vivo evidence that Nampt transgene aggravates atherosclerotic inflammation and promotes atherosclerosis development in ApoE −/− mice.

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“…Nicotinamide as an essential component of NAD/ NADH (reduced NAD) drives the electron transport chain converting the free energy of the electromotive force in to a proton gradient across the mitochondrial inner membrane driving ATP production and controlling pH and other voltagecoupled processes. [145][146][147][148] Simultaneously, many NAD-coupled redox reactions as well as more recently discovered NADconsuming reactions are known to be important for cell development, repair, and ageing: NAD is a master controller of much of metabolism necessary for running large bodies and brains and restoring stem cells. 70,[149][150][151][152][153][154][155] High energy has long been recognised as crucial for expanding ape brain size but has often been considered to be paid for by reducing energy spent on large guts, inefficient locomotion, and less chewing.…”

Section: Meat -The Key Ingredient Is Nicotinamidementioning

confidence: 99%

Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

Williams

Hill

2017

Int J�Tryptophan�Res

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Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B3 / nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.

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Reassessing the role of NAD as a prosurvival factor

Cited by 3 publications

References 10 publications

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Nicotinamide phosphoribosyltransferase aggravates inflammation and promotes atherosclerosis in ApoE knockout mice

Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

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Reassessing the role of NAD as a prosurvival factor

Cited by 3 publications

References 10 publications

Meat Intake and the Dose of Vitamin B3– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Meat Intake and the Dose of Vitamin B3– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Nicotinamide phosphoribosyltransferase aggravates inflammation and promotes atherosclerosis in ApoE knockout mice

Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics

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Product

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Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Meat Intake and the Dose of Vitamin B₃– Nicotinamide: Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?