Page Synopsis: Extremely promising though in my experience it had little effect

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From: ''NAD: The Biological Rocket Fuel that Gives You Energy''


NAD deficiency has long been implicated in numerous chronic inflammatory diseases. It's even being used successfully in drug rehabilitation programs now to ease withdrawal symptoms.


It kind of seems like a miracle so I'm curious why more studies haven't been done using it with the MECFS population.


At this point, it's really, really expensive. Treatments typically run $1000+ for each IV session and usually a minimum of 4 sessions are recommended for CFS. There are clinics that offer less expensive versions but (of course) the people hawking the more expensive BR+ (brain restoration) version insist that theirs is the only effective way to produce the NAD and the price won't come down until the compounding pharmacy that developed it has recouped their investment.


All that makes me scratch my head a little bit because it seems like they could recoup their investment faster if it worked and more people did it at a lower price too.


So is it really all that and a bag of chips? Or just another expensive rip off? I sure wish I knew!

From MindBody Medicine Center


NAD stands for nicotinamide adenine dinucleotide, which is the chemical term for a molecule that reacts with oxygen in the mitochondria in every cell of your body in order to create energy so you can move, breathe, pump blood, digest food, think, and generally, live your life.


Lack of this essential cellular fuel is now recognized as a key feature of chronic fatigue, apathy, depression, anxiety, alcohol and drug addiction, weak immune system (infections and cancer), muscle pain and weakness, headaches, memory disturbance, sleep problems, focus and concentration defects and other chronic diseases. NAD deficiency may be an unrecognized epidemic of cellular disease.


NAD is an activated form of vitamin B3 which becomes a coenzyme when it is bound with hydrogen becoming NADH. Hydrogen, as in hydrogen bomb, is the explosive power that the body uses, along with oxygen, to make energy. Liquid hydrogen and liquid oxygen explode when blended together becoming the fuel that propels rockets into the sky. Hydrogen is so explosive that it must be safely inserted into a molecule so that it can be used by the body. NAD is the carrier for reactive hydrogen as it becomes NADH.


This is how it works. We eat carbohydrates, proteins and fats which provide the chemicals that enter the Citric Acid Cycle, a molecular roundabout that produces NADH. The NAD is now “loaded” with hydrogen (NADH) which in turn enters the electron transport chain in the mitochondria and is “sparked” with oxygen and the outcome is energy, or, ATP, along with water. ATP, or adenosine triphospate, is the fuel for the heart to beat, the muscles to contract and for every cellular energy requirement with in the 100 trillion cells of the body.


It is clear to see how important NADH is for the body as it is involved in every bodily function and catalyzes more than a thousand metabolic reactions in the organs and tissues. The heart uses the most NAD as it beats around 86,000 times daily. The brain consumes about one-third of all the energy produced by the body. Often an energy deficiency is first detected in the brain with poor concentration, difficulty focusing, and attention deficit. If the energy shortage lasts long enough, brain neurons cannot synthesize neurotransmitters, the molecules of consciousness, such as serotonin, dopamine, and noradrenaline, and we experience anxiety, depression, sleep disturbance and other mood changes.


Let us take a look at some of the functions of NADH in the body:


  • Increases energy in heart cells
  • Increases energy in brain cells
  • Protects and repairs DNA, reducing DNA mutations which contribute to atherosclerosis, cancer, immunodeficiency, rheumatoid arthritis, and much more
  • The “most powerful antioxidant” in the body according to Dr. Richard Passwater in his book NADH-The Energizing Coenzyme
  • Lowers cholesterol
  • Lowers blood pressure
  • Strengthens the immune system
  • Stimulates production of dopamine, serotonin, and noradrenaline, thereby improving moods
  • Stimulates nitric oxide production, thereby improving blood flow in the body


Research has shown the following medical conditions to improve with NAD therapy:


  • Chronic fatigue
  • Muscle pain and weakness
  • Joint pain and stiffness
  • Headaches
  • Depression
  • Anxiety
  • Alcohol and drug addiction
  • Diabetes
  • Sleep disturbance
  • Memory loss (forgetfulness)
  • Attention deficit
  • Fevers, sore throats and swollen lymph glands
  • Parkinson’s disease
  • Cancer


Research has also shown that NAD can provide the following benefits in “healthy” people:


  • Increased physical energy
  • Improved mental performance
  • Improved response to short term sleep deprivation
  • Reduce the effects of jet lag
  • Anti-aging
  • Enhance libido


Since NAD is so fundamental to good health, how is it that we can become deficient in this powerful molecule?


First of all, the vitamins, minerals, complex carbohydrates, proteins and fats come from our diet and provide the building blocks to citric acid cycle energy production. If any one of the nutritional factors is low, energy production is weakened. Since oxygen is just as important as hydrogen in cellular energetics, lack of exercise and shallow breathing due to stress are common factors that can reduce the amount of oxygen at the cell level. And finally the enzymes that catalyze the citric acid cycle are often inhibited or destroyed by chemical or physical toxins that create oxidative, or free radical, damage.


Free radical damage comes from cigarette smoke, drugs, radio waves from cell phones and wi-fi, and the myriad chemicals found in all humans at this time on earth, including phalates, parabens, pesticides, styrene, benzene, toluene, and thousands more. For example, medical scientists now widely believe that Alzheimer’s dementia and Parkinson’s disease share the common feature of nerve cell degeneration due to impairment of the ATP producing enzymes with the citric acid cycle and mitochondria.


However, there is more than acquired NAD deficiency, due to poor diet, chronic stress, sedentary living and toxin accumulation so common in our modern world – it may also be genetic for some people. Genetic NAD deficiency may be present at birth and appear in children as poor sleeping, behavioral problems, hyperactivity, impaired concentration, academic stress and underachievement.


Some people have been tired and depressed for as long as they can remember. For these people there is a greater tendency to try drugs and alcohol in order to improve energy and mood, and simply feel better, but the risk for addiction is high. I have treated several people addicted to drugs, alcohol or medical drugs such as benzodiazapenes, like Valium, Librium and Klonopin, with intravenous NAD, thereby eliminating the addiction and leading to improved energy and moods in the long run.


Genetic disorders in energy production are complex and the research is accumulating to help us understand this important issue. There may be a genetic polymorphism that reduces a gene coding for a mitochondrial protein. Since mitochondrial DNA is all received from the mother through the egg (no mitochondria are found in sperm) we can look to the maternal side for clues to energy production in the family history.


How do we diagnose NAD deficiency? Fatigue is often the first signal, but there are many conditions in the body that present as fatigue, such as low thyroid. The following clues are used in making a diagnosis of NAD deficiency:


Family history

  • Fatigue and depression, mainly on the mother’s side


Personal history

  • Fatigue and/or depression beginning early in life, such as childhood or teen years
  • Alcohol or drug addiction
  • Chronic fatigue any time in life
  • Depression and anxiety
  • Almost any chronic disease


Traditional blood tests measure NAD

Lactic acid and pyruvate (blood):

  • Pyruvic acid comes from foods and supplies energy to the citric acid cycle when oxygen is present and alternatively ferments to produce lactic acid when oxygen is lacking (fermentation). Therefore elevated lactic acid or pyruvate may be a signal of NAD deficiency.


Specialty lab tests

  • Organic Acid testing (urine) is available from Genova Diagnostics, Great Plains Laboratory and Metametrix Clinical Laboratory:
  • Pyruvate and lactic acid can also be measured in a first-morning urine.


Citric Acid Cycle Intermediates are organic acids found in the urine that directly reflect CAC activity and when elevated indicate CAC dysfunction and reduced NADH. There are many metabolic reasons for elevated CAC intermediates.


Citric Acid Cycle Intermediates include the following:

  • Citric acid
  • Cis-Aconitic acid
  • Isocitric acid
  • Alpha-ketoglutaric acid
  • Succinic acid
  • Malic acid
  • Beta-hydroxy-beta-methylglutaric acid


How do you treat NAD deficiency?

First of all NAD is in many of the foods that we eat, but it is mostly lost in cooking and what little remains is broken down by the acid in our stomachs. Many research scientists have observed that NAD is oxidized and degraded before it is absorbed from the digestive tract. More recent studies have shown that NAD can be provided in a stabilized form and will increase ATP production in the body and in the brain, thereby offering hope to patients with neurodegenerative disorders.


For patients with severe NAD deficiencies, such as alcoholics or drug addicts, the intravenous form has been shown to be highly effective, usually eliminating the physical craving within three or four days and then producing a clarity of thinking with continued daily IV therapy. The cognitive and emotional improvement is likely due to increased production of neurotransmitters such as serotonin, noradrenalin and dopamine. Numerous studies have shown that IV NAD is highly beneficial for drug addicted patients, including those addicted to benzodiazepine medications like Valium, Librium and Klonopin.


Intravenous therapy for four to six days is often beneficial to people with chronic depression, often unresponsive to antidepressant therapies.


There is now a new form of oral NAD that is proving highly beneficial to patients with NAD deficiency and the widespread problems with adequate cellular energy production.


In the future, NAD therapy will likely prove beneficial for a range of common medical problems, including fatigue, jet lag, mood disorders, menopausal symptoms, obesity and more. Like aerobic exercise and healthy whole food nutrition, NAD therapy offers a foundational treatment that promotes health throughout the body.

From: Healthrising user doerfast on 'NAD: The Biological Rocket Fuel that Gives You Energy'


The following are precursors (raw materials) from which NAD+ can be produced:

  • Nicotinamide Riboside (NR)
  • Tryptophan (L-Trp)
  • Nicotinic Acid (NA, Vitamin B3)
  • Nicotinamide (NAM, also called no flush Niacin)
  • Nicotinamide Mononucleotide (NMN)


NAD supplement does NOT cross the mitochondria inner membrane. NAD+ (the oxidized form of NADH ) does not enter the cell. NADH is the only moleciule that passes the cell membrane and increases the ATP energy in the cell. In the cell NADH is oxidized to NAD\* and water. Hence NADH is the only molecule able to increase intracellular levels of NAD+. NR is a charged molecule and a charged molecule can not penetrate a lipid membrane such as the cell membrane. NADH penetrates the cell membrane and increases ATP in the cell (see attached publication). On Fig. 4 you can see that only NADH but neither Nicotinamide nor NAD+ goes into the cell and increases ATP energy there.


NADH cannot simply pass into mitochondria for oxidation by the respiratory chain, because the inner mitochondrial membrane is impermeable to NADH and NAD+. The solution is that electrons from NADH, rather than NADH itself, are carried across the mitochondrial membrane. One of several means of introducing electrons from NADH into the electron transport chain is the glycerol 3-phosphate shuttle (Figure 18.37). The first step in this shuttle is the transfer of a pair of electrons from NADH to dihydroxyacetone phosphate, a glycolytic intermediate, to form glycerol 3-phosphate.This reaction is catalyzed by a glycerol 3-phosphate dehydrogenase in the cytosol. Glycerol 3-phosphate is reoxidized to dihydroxyacetone phosphate on the outer surface of the inner mitochondrial membrane by a membrane-bound isozyme of glycerol 3-phosphate dehydrogenase. An electron pair from glycerol 3-phosphate is transferred to a FAD prosthetic group in this enzyme to form FADH2. This reaction also regenerates dihydroxyacetone phosphate.

From discussion 'Anyone Tried NADH for Energy?' on

hi, I have just order a product which says its better absorbed then nadh, its called nad. it says its not altered by the acids in the stomach, what doesnt make sense is its subligual so u would think that stomach acid wouldnt be a problem. Anyway im going to give it a try and see how it go's, its now brand from iherb , i have had some response from normal nadh 20mg sublingual, like a caffeine hit i suppose. Anyone else tried this version? be interested to know how u went. The reviews on iherb were very positive but suppose there biast too, lol.

From: PhoenixRising user pemone on 'Anyone Trying Niagen?'

The points below run the risk of being a little obscure to some of you, but this issue strikes me as one that should be among the top three discussions in a CFS forum. Yet, no one here is discussing this. No one is experimenting with Niagen. How can this be?


Read point number one of 10 by James Watson in this article:


The number one anti-aging story of 2013 was that "...mitochondrial dysfunction and...Warburg-type metabolism are fully reversible with the supplementation of NAD+ precursors."


Cancer is the ultimate expression of a cell that is fueled by glucose, and does not need mitochondria. CFS is similar however, because somehow the mitochondria are not functioning well, and the cell is being forced to rely on glucose metabolism. Because that is inefficient, many metabolic processes run out of energy.


Cancer is a special case because the mitochondria get permanently damaged and basically the cell takes on a metabolism that no longer needs mitochondria. But CFS involves cells with mitochondria that are still intact. In theory, CFS might respond very well to the generation of more NAD+.


This is the key point. By whatever means (still not determined), the cells of the CFS sufferer are relying on glucose metabolism, and insufficient NAD+ is produced. Insufficient NAD+ means insufficient ATP production. Insufficient ATP means many cellular processes run too slowly to be effective.


What is exciting about the Watson article is that he is saying we may have chemical ways to reverse this NOW. Watson points out that there are two precursors to NAD+


1) A precursor that is one step away from NAD+ named NMN, but this is very expensive and not available.


2) A precursor that is two steps away from NAD+ named Nicotinamide Riboside (NR). Proprietary name is Niagen. I found a supplier online and it is not cheap, but if it works who wouldn't pay it?


Watson quotes a study by David Sinclair at Harvard in which mice were given NMN, and all of their age-related defects in NAD+ production reversed, quickly. He points out that there are no experiments with Niagen, but he wonders if this won't have the same effect.




1) Have any of you experimented with Niagen / NR, and what was the result?


2) What is the recommended dose for a CFS sufferer? Does it need to be spread out over the day, to support metabolism continuously, or can the body buffer a single dose?


3) Is it necessary to take NR together with other specific vitamins, in order to prevent other B vitamins to be dysregulated?


4) Is there any way to profile our blood cell profile of NAD+, NADH, and the levels of chemicals and enzymes in the pathway(s) that create NAD+?


I see NR / Niagen mentioned in only a few threads here. I'm shocked that this isn't a much bigger topic. This holds out potential to be a cure.


The disease we have seems to downregulate NAD+ production, which leads to all kinds of problems creating ATP. The Watson article is suggesting ways we can fix the NAD+ problem quickly and easily.

From: PhoenixRising user stevesayshi on 'Anyone Trying Niagen?'


I took a gram (8 caps) today.

It did... something. I was furious all day -- but it was like the old fire in my body was turned back on. I was hot in cold rooms, like I was, hell, I want to say before I got sick, but really even further back than that. I decided to go to a casino and play poker like I used to (since I got sick, the most I could manage was about an hour without a mini crash). I felt immune to any adrenaline rush and played for 6 hours. Will take 1 gram tomorrow and let you know how it goes.


Many people on longecity report severe fatigue after taking large doses for several days, ha ha I'd love to see that.


Edit: I don't think it will be a \*cure\*. Seemed to have no impact on non-fatigue symptoms. May take a lot longer to reverse those. Muscle pain in particular was bad today.


Reply from user rwac

Niacinamide lowers free fatty acids, and increases dependency on carbs. I wonder if that muscle pain isn't muscle being sacrificed to keep you burning carbs, assuming NR works similarly to niacinamide. I wonder if people who crash on NR aren't low carbing.


Reply from user pemone

Are you sure what you are experiencing as muscle pain isn't just some acid from exercise that is not clearing from the muscle?


In reading about this some more: "...excess niacin (B3) is metabolized by methylation and thus uses up methyl groups. So if you are an over-methylator, meaning you have extra, then B3 is good because it uses them up, but if you are an under-methylator, meaning deficient, then giving extra B3 is bad because it drains an already poor supply."


That seems to imply we shouldn't try to solve the NAD+ creation problem in isolation. We need to understand our MTHFR defects and our methylation status and fit the NAD+ supplementation into that bigger picture.


In my own case, I have high homocysteine. That suggests a possible methylation issue, and taking niacinamide in high doses might stress my system even more and send my homocysteine even higher.


Reply from user stevesayshi

I don't believe NR uses up methyl groups in the same way niacin does. Could be wrong. Have no idea what my methylation status is. I believe I was probably low for a long time and have now entered some wild swing between high and low. Is muscle pain associated with under or overmethylation? Speaking of which, I used to think it was lactic acid but not so sure now.


Day 2. Not angry today. It's clear this does more for my mental energy than physical.

I bought some a month ago and reordered it. It seems to help with a more awake and on-feeling. One of the very few supplements that has done anything. Very expensive. They have a group buy effort going on at Longecity, which lowers the price.




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