Alberts B, et al. Energy Conversion: Mitochondria and Chloroplasts. Molecular Biology of the Cell. 3rd Edition. Garland Publishing, Inc; 1994:653-720.
Birkmayer JG. Coenzyme nicotinamide adenine dinucleotide: New therapeutic approach for improving dementia of the Alzheimer’s type. Ann Clin Lab Sci. 1996;26(1):1-9.
The Coenzyme nicotinamide adenine dinucleotide (NADH) has been used as medication in 17 patients suffering from dementia of the Alzheimer type in an open label trial. In all patients evaluated so far, an improvement in their cognitive dysfunction was observed. Based on the minimental state examination, the minimum improvement was 6 points and the maximum improvement 14 points with a mean value of 8.35 points. The improvement on the basis of the global deterioration scale (GDS) was a minimum of 1 point and a maximum of 2 points with a mean value of 1.82. The duration of therapy was between 8 and 12 weeks. No side effects or adverse effects have been reported from the patients or their caregivers during the observation period which is, in some patients, more than a year. This open label trial represents a pilot study from which no definitive conclusion can be drawn. A double-blind placebo controlled study is necessary to demonstrate the clinical efficacy of NADH. The planning and the fulfillment of all requirements for such a study are in progress.
Reinikainen KJ, et al. Neurotransmitter changes in Alzheimer’s disease: implications to diagnostics and therapy. Neurosci Res. 1990;27:576-86.
Changes in the cholinergic, serotonergic, noradrenergic, dopaminergic, GABAergic and somatostatinergic neurons were investigated to determine their roles in Alzheimer’s disease (AD). Markers for these systems were analyzed in postmortem brain samples from 20 patients with AD and 14 controls. In the CSF study, markers for the cholinergic neurons (choline esterase, ChE) and for the somatostatinergic neurons (somatostatin-like immunoreactivity, SLI) were assayed for 93 and 75 probable AD patients and 29 and 19 controls, respectively. Activity of choline acetyltransferase (CAT) was decreased by 50-85% in four cortical areas and hippocampus in patients with AD, but not in other areas of the brain, indicating a profound deficit in the function of cholinergic projections ascending from the nucleus basalis to the cerebral cortex and hippocampus in AD. Muscarinic receptor binding was reduced by 18% in the frontal cortex but not in other areas of the brain in AD. Serotonin (5HT) concentrations were reduced (by 21-37%) in hippocampal cortex, hippocampus and striatum; and 5HT metabolite levels were lowered (by 39-54%) in three cortical areas, thalamus and putamen in AD patients. Concentrations of noradrenaline (NA) were reduced (18-36%) in frontal and temporal cortex and putamen. These data imply that serotonergic and noradrenergic projections are also affected in AD but less than the cholinergic neurons. Dopamine (DA) concentrations in AD patients were reduced by 18-27% in temporal and hippocampal cortex and hippocampus, while HVA, the metabolite of DA, was unaltered. Glutamic acid decarboxylase activity was not altered in AD. SLI was decreased (28-42%) in frontal, temporal and parietal cortex, but not in thalamus and putamen in patients with AD. Frontal tangle scores correlated most strongly with cortical CAT activity reduction and less so with decreases of 5HT, NA and DA, indicating a closer correlation with the cholinergic changes and severity of AD than with other neurotransmitter deficiencies. ChE activity and SLI were reduced by 20% and 35%, respectively, in CSF of the whole group of AD patients as compared to the controls. Comparison of CSF findings between four subgroups of dementia severity indicated that the SLI was already reduced in the group of mildest AD (-31%), while ChE activity was not. Although ChE activity in CSF declined in relation to dementia severity, however, the maximal reduction was only modest (-30%). On the other hand, SLI in CSF showed only a slight further reduction (up to -41%) as the dementia become more severe.(ABSTRACT TRUNCATED AT 400 WORDS)
Forsyth LM, et al. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol. Feb1999;82(2):185-91.
BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like symptoms, myalgia, weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and swelling and tenderness of lymph nodes. No effective treatment for CFS is known.
OBJECTIVE: The purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral absorbable form, in a randomized, double-blind, placebo-controlled crossover study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger energy production through ATP generation which may form the basis of its potential effects.
METHODS: Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS completed the study. Medical history, physical examination, laboratory studies, and questionnaire were obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the alternate regimen for a final 4-week period.
RESULTS: No severe adverse effects were observed related to the study drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Based upon these encouraging results we have decided to conduct an open-label study in a larger cohort of patients.
CONCLUSION: Collectively, the results of this pilot study indicate that NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and suggest that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.
Birkmayer JG, et al. The coenzyme nicotinamide adenine dinucelotide (NADH) as biological antidepressive agent experience with 205 patients. New Trends in Clinical Neuropharmacology. 1991;5:75-86.
Kay GG, Virre E, Clark J. Stabilized NADH as a countermeasure for jet lag. 48th International Congress of Aviation and Space Medicine. Rio de Janeiro. Sep2000.
Birkmayer JG, et al. Stimulation of the endogenous L-Dopa biosynthesis – a new principle for the therapy of Parkinson’s Disease: The clinical effect of nicotinamide adenine dinucleotide (NADH) and nicotinamide dinucleotidephosphate (NADPH). Acta Neurol Scan. 1989;126:183-187.
The coenzyme nicotinamide adenine dinucleotide (NADH) has been used as a novel medication in 161 Parkinson patients in an open label trial. In all but 18 patients (11.2%) an improvement in their disability was observed. 115 patients (71.4%) showed a very good (better than 30%) response, and 28 patients (17.4%) a moderate response up to 30%. The best results were obtained with a dose of 25 to 50 mg every second day by i.v. administration. Concomitantly with the improvement in disability, the urine HVA level increased significantly, indicating a stimulation of endogenous L-DOPA biosynthesis. 8 patients have been treated with nicotinamide adenine dinucleotidephosphate (NADPH), 5 of whom exhibited an improvement in their disability from 35 to 55%. The other 3 showed a moderate response of 20 to 25%. In all these patients an increase in the urine level of HVA was detected, reflecting elevated endogenous L-DOPA production.
Birkmayer JG, et al. Nicotinamide adenine dinucleotide (NADH) – a new therapeutic approach to Parkinson’s Disease, Comparison of Oral and Parenteral Application. Acta Neurol. Scan. 1993;87(Suppl146):32-35.
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.
Birkmayer JG, et al. Nicotinamide adenine dinucleotide (NADH) as medication for Parkinson’s Disease. Experience with 415 patients. New trends in clinical neuropharmacology. 1990;4(1):7-24.
Alberts B, et al. Energy Conversion: Mitochondria and Chloroplasts. Molecular Biology of the Cell. 3rd Edition. Garland Publishing, Inc; 1994:653-720.
Originally discovered in 1905 in yeast, NADH is also known as the reduced form of coenzyme 1, a complementary enzyme utilized in the production and regulation of energy (oxidative phosphorylation). [ Ref. ] A coenzyme is the active or working form of a vitamin. NADH is the reduced (electron-energy rich) coenzyme form of vitamin B3; while NAD is the oxidized (burned) coenzyme form of vitamin B3. NAD and NADH are converted into each other in numerous different metabolic activities. In some metabolic reactions, it is NAD which is the needed catalyst, with NADH a useful by-product; in other reactions the situation is reversed.
NAD and NADH also serve to activate various enzymes. NADH is the first of five enzyme complexes of the electron transport chain where much of the ATP bioenergy that runs every biological process of the body is formed.
NADH is necessary to oxidize all foodstuffs (fats, sugars, amino acids) into ATP bioenergy. As all living cells require energy to survive, NADH reacts with oxygen to form water and energy. One molecule of NADH yields three molecules of ATP (the stored form of energy), with the amount of NADH present dictating the amount of energy produced. The heart muscle cells contain 90mcg of NADH per gram of tissue, with brain and muscle tissue containing 50mcg per gram. Even red blood cells contain NADH with 4mcg per gram. The more NADH present in cells, theoretically, the more efficient they function in energy production.
NADH was never really considered as an oral dietary supplement due to its high reactivity and probable degradation in the blood. However, a stable, disodium salt oral form of NADH has been introduced and used clinically with reported effectiveness.
B-nicotinamide adenine dinucleotide; disodium salt form.
NAHD is readily absorbed from the intestinal tract.
Toxicities & Precautions
NADH is generally considered to be safe in recommended dosages.
Functions In The Body
Cellular energy production – involved in ATP production via oxidative phosphorylation.
Cell regulation and DNA repair – genetic codes may become damaged by various toxins and environmental stresses such as radiation, UV light, ozone, and chemical toxins (including certain pharmaceutical drugs).
Enhances cellular immunity – useful in Chronic Fatigue Syndrome and in athletes.,
Antioxidant – protects cells against free radical damage.
Stimulator of dopamine, norepinephrine, and other catecholamine production – stimulatory effects, potentially increasing athletic performance and of benefit in Parkinson’s, Alzheimer’s Disease, and Chronic Fatigue Syndrome.
Seventeen patients suffering from dementia of the Alzheimer’s type in an open-label trial were treated with the disodium salt of NADH, 10mg daily. [ Ref. ] Improvement in cognitive function was reported in all patients. Using NADH as a therapeutic choice in the management of dementia is based on the theory of the stimulation of the biosynthesis of endogenous neurotransmitters, in particular dopamine and norepinephrine. This should improve the mental performance of patients with cognitive dysfunction and/or dementia, as these neurotransmitters are reduced in certain areas of the brain in Alzheimer’s patients. [ Ref. ]
The FDA approved a clinical trial at Georgetown University Medical Center to investigate the treatment of Alzheimer’s Disease with disodium NADH. Preliminary results from the study have indicated promising outcomes and warrant further research.
Chronic Fatigue Syndrome
Characterized by a combination of flu-like symptoms including extreme fatigue, myalgia, impairment of short term memory, sleep disturbances, mild fever, and sore throat, Chronic Fatigue Syndrome affects millions of Americans, 70 percent of whom are women. Symptoms must persist for more than six months in order to comply with the definition of Chronic Fatigue Syndrome. A 12-week, double-blind, placebo controlled study reported very positive results using NADH in the management of Chronic Fatigue Syndrome. [ Ref. ] Thirty-one percent of the patients who took the nutritional supplement reported improvement in symptoms, versus 8 percent in the placebo group. The dosage regimen of NADH was 10mg daily for four weeks on, four weeks off. The proposed mechanism of action of NADH in this disease is the replenishment of depleted cellular stores of ATP, thus improving the fatigue and cognitive dysfunction associated with Chronic Fatigue Syndrome.
Additionally, in a follow-up preliminary open-label study, 73 percent of the patients achieved marked improvement over time. Researchers identified no adverse effects from taking the disodium NADH product and no reportable drug interactions.
NADH was used in an open-label trial of 205 patients suffering from depression with various clinical symptoms. [ Ref. ] NADH was given either orally (5mg daily) or by intramuscular or intravenous injection, with the duration of therapy lasting five to 310 days. Ninety-three percent of the patients exhibited beneficial clinical effects. Benefits were attributed to the positive effects that NADH has upon the synthesis of L-dopa, dopamine, norepinephrine, and other catecholamines.
In a double-blind study, subjects taking a “red-eye” flight spanning four time zones were tested with sublingual NADH or a placebo. The subjects who used the sublingual NADH tablets performed better on measurements of cognition and sleepiness compared to placebo controls and there were not any side effects. [ Ref. ]
Several studies have reported benefits in the use of NADH in Parkinson’s patients. [ Ref. ] , [ Ref. ] In an open-label trial of 415 patients with Parkinson’s Disease, NADH was given in its stable form as 5mg every other day for two weeks. Mobility, in particular walking, pushing, posture, and speech, as well as the ability to mimic another’s speech, showed improvement. [ Ref. ] Research has reported that NADH stimulates endogenous L-dopa synthesis, the precursor of dopamine. [ Ref. ]
Symptoms and Causes of Deficency
NADH is not an essential nutrient for humans and a deficiency condition has not been identified.
NADH occurs in many consumable foods, including red meats, poultry, fish, and products with yeast (such as breads).