ENADA NADH 5 mg by Prof. Birkmayer Health Products USA

POSSIBLY EFFECTIVE

• Chronic fatigue syndrome (CFS). Several small clinical studies suggest that oral NADH, taken alone or in combination with coenzyme Q10, modestly improves symptoms of CFS. Details: One small clinical study in patients with CFS shows that taking NADH 10 mg daily for 4 weeks leads to a favorable response in around 31% of patients, compared with around 8% of those taking placebo (8267). Another small clinical study in patients with CFS shows that taking NADH 5-10 mg daily for 24 months reduces symptoms by 42% when compared to baseline in the first 3 months, with symptom scores maintained for the rest of the study. These results were similar to patients receiving conventional treatment with nutritional and psychological interventions (93687). NADH has also been evaluated in combination with other ingredients. A small clinical study in patients with CFS shows that taking a specific product (ReConnect, Vitae Natural Nutrition) containing NADH 10 mg plus coenzyme Q10 100 mg twice daily for 8 weeks reduces fatigue index scores by about 6%, compared with about 3% in those taking placebo (93686). A larger clinical study also shows that taking NADH 20 mg plus coenzyme Q10 200 mg daily for 8 weeks improves some measures of fatigue, sleep quality, and quality of life when compared with baseline. No improvements in these measures were reported with placebo (107448). It is unclear if these findings are due to NADH, coenzyme Q10, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral NADH for aging, there is insufficient reliable information about the clinical effects of NADH for this purpose.
• Alcohol-related liver disease. Although there has been interest in using oral NADH for alcohol-related liver disease, there is insufficient reliable information about the clinical effects of NADH for this purpose.
• Athletic performance. Although there has been interest in using oral NADH for improving athletic performance, there is insufficient reliable information about the clinical effects of NADH for this purpose.
• Cognitive function. Although there has been interest in using oral NADH for improving various measures of cognitive function, including memory and mental alertness, there is insufficient reliable information about the clinical effects of NADH for this purpose.
• Dementia. It is unclear if oral NADH is beneficial in patients with dementia. Details: A small clinical study in patients with mild to moderate dementia of the Alzheimer, vascular, or fronto-temporal type shows that taking NADH 10 mg daily for 12 weeks does not improve measures of memory, cognition, or behavioral function when compared to baseline (8275).
• Depression. Although there has been interest in using oral and parenteral NADH for depression, there is insufficient reliable information about the clinical effects of NADH for this purpose.
• Hypertension. Although there has been interest in using oral NADH for hypertension, there is insufficient reliable information about the clinical effects of NADH for this purpose.
• Jet lag. Although there has been interest in using oral NADH for jet lag, there is insufficient reliable information about the clinical effects of NADH for this purpose.
• Parkinson disease. Small, low-quality studies have yielded conflicting findings regarding the effects of oral or parenteral NADH in patients with Parkinson disease. Details: A very small, double-blind, placebo-controlled clinical trial in patients with Parkinson disease shows that administering intravenous NADH 25 mg daily for 4 days followed by intramuscular NADH 25 mg at weeks 2 and 4 does not improve Unified Parkinson Disease Rating Scale (UPDRS) scores when compared with placebo (3090). However, a large, open-label clinical study in patients with Parkinson disease shows that taking NADH 5 mg by mouth or administering intravenous NADH 12.5 mg over 30 minutes every other day for 14 days reduces disability scores by between 30% and 50% in around 19% of patients and reduces scores by between 10% and 30% in around 59% of patients when compared with baseline (3089). Also, a smaller, open-label clinical study in patients with Parkinson disease shows that administering intravenous NADH 10 mg over 30 minutes once daily for 7 days improves symptoms as measured by the UPDRS and increases the bioavailability of levodopa when compared with baseline (3086). The validity of the findings in these open-label studies is limited by a lack of placebo control. More evidence is needed to rate NADH for these uses.

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LIKELY EFFECTIVE

• Dyspepsia. Over-the-counter oral antacid products containing sodium bicarbonate are considered effective by the US Food and Drug Administration (FDA). Details: Over-the-counter oral antacid products containing sodium bicarbonate are considered effective by the US Food and Drug Administration (FDA) when taken for up to 2 weeks at a maximum daily dosage of 200 mEq sodium and 200 mEq bicarbonate by patients up to 60 years old and when taken at a maximum daily dosage of 100 mEq sodium and 100 mEq bicarbonate by patients over 60 years old (90912).

POSSIBLY EFFECTIVE

• Athletic performance. Oral sodium bicarbonate seems to improve athletic performance in most populations. It is unclear if topical or intravenous sodium bicarbonate is beneficial for athletic performance. Details: Although conflicting research exists, oral sodium bicarbonate seems to improve athletic performance in males and females. This conclusion is the position of the International Society of Sports Nutrition (ISSN) based on a comprehensive review of the literature (106250). The greatest evidence of benefit, with the lowest risk of adverse effects, is shown for single-dose protocols using 300 mg/kg 60-180 minutes before exercise, or protocols involving intakes of 100-200 mg/kg 2-3 times daily for 3-7 days, for a total daily dose of 400-500 mg/kg. Generally, increasing the dose of sodium bicarbonate above 300 mg/kg does not improve athletic performance and may increase the severity of gastrointestinal adverse effects (25706,104850,106250). Multiple meta-analyses of clinical research in male athletes and non-athletes shows that acute doses of oral sodium bicarbonate, taken as 200-400 mg/kg 40-120 minutes prior to exercise, improves mean performance on sprint exercises by 2% to 16% when compared with controls (25706,104847). Another meta-analysis shows that oral or intravenous sodium bicarbonate 100-400 mg/kg, taken within 3 hours of exercise, modestly improves exercise performance, total work, performance time, and power, and increases time to exhaustion when compared with placebo (25707). Although the majority of research has been conducted in males, most available evidence also supports the ergogenic effects of sodium bicarbonate in females (25706,106250,106252). In general, the ergogenic benefits of sodium bicarbonate have been shown in muscular endurance-type activities, as well as high-intensity activities, such as cycling and running, and are especially relevant for single exercise sessions lasting 30 seconds to 12 minutes or for repeated exercise measures (106250). One meta-analysis of clinical research shows that sodium bicarbonate does not improve mean power during sprint tests lasting 10 minutes or longer (25706). Also, although some individual research disagrees (104849), meta-analyses of research assessing athletic performance on Wingate tests, generally lasting up to 30 seconds, shows that acute sodium bicarbonate ingestion does not improve peak or mean power when compared with placebos such as calcium carbonate or sodium chloride (101265,106243). However, it does produce modest improvements in these measures for repeated performance (106243) or when ingested for 5-7 days (101265). In addition to cycling and running, the ergogenic benefits of sodium bicarbonate have been shown in some studies for activities such as swimming and rowing (106250). Although a small study in highly trained rowers found no benefit with sodium bicarbonate (97732), more recent research and a meta-analysis shows that taking sodium bicarbonate 100-300 mg/kg up to 4 hours prior to competition seems to be beneficial for improving mean power during a 2000-meter rowing performance (106245,106250,106253). Also, in elite level rowers, clinical research shows that taking sodium bicarbonate 300 mg/kg prior to competition, on an individualized schedule based on time to peak bicarbonate levels, improves rowing performance when compared with using a standardized administration time of 60 minutes prior to performance (106245). The ergogenic effects of sodium bicarbonate have also been shown for middle-distance, but not short-distance, swimming competitions (106249,106250). A meta-analysis of small clinical trials shows that taking sodium bicarbonate 200-300 mg/kg 60-120 minutes prior to competition has a small benefit on 200-meter and 400-meter swim tests, but not on tests of 100 meters or less (106249). Research related to the ergogenic effects of sodium bicarbonate for combat sports or martial arts is mixed (106244,106250,109691). Although the ISSN have suggested that the available clinical research shows that sodium bicarbonate is beneficial for combat sports (106250), a recent meta-analysis of clinical research in combat sport athletes, including judo, wrestling, and others, shows that sodium bicarbonate as single or multiple doses does not improve athletic performance, power, or perceived exertion when compared with placebo (109691). Also, a small clinical trial in jiu-jitsu athletes shows that taking sodium bicarbonate before testing does not improve muscle contractions (106244). One meta-analysis suggests that the ergogenic effects of sodium bicarbonate are associated with the degree of alkalosis (25707). However, initial research in male athletes shows that although taking 200 mg/kg sodium bicarbonate for 8 days does not significantly increase blood pH, it still improves performance on the Wingate test when compared with a single dose (104849). More research is needed to determine if taking sodium bicarbonate during training improves adaptations to exercise or whether sodium bicarbonate is beneficial in multi-sport or multi-day events (106250). Sodium bicarbonate has also been investigated in combination with other ergogenic compounds. There is some clinical evidence showing that combining sodium bicarbonate with beta-alanine or creatine may have additive effects (106250). Although most of the individual studies disagree with these findings, one meta-analysis of small clinical trials shows that taking a combination of sodium bicarbonate, usually a single dose, along with beta-alanine has a moderately greater ergogenic effect than taking beta-alanine alone (94357). Also, a small number of individual studies shows that taking sodium bicarbonate as a single dose or along with creatine improves performance in various sports (106250). More research is needed to determine any additional benefit of combining sodium bicarbonate with caffeine or nitrates (106250). Topical sodium bicarbonate has also been evaluated. Preliminary clinical research in healthy adults shows that topical application of 0.9036 grams/kg of sodium bicarbonate as a specific sodium bicarbonate 33.2% lotion (PR Lotion; Amp Human Performance) 30 minutes prior to exercise does not improve performance on the Wingate test when compared with placebo. This lotion also led to smaller increases in blood pH and bicarbonate ion levels when compared with a single oral dose of sodium bicarbonate 0.3 grams/kg (104848).
• Drug-induced sodium channel blockade. Intravenous sodium bicarbonate seems to be beneficial for the management of drug-induced sodium channel blockade. Details: Preliminary clinical studies show that intravenous sodium bicarbonate treats QRS widening following exposure to various drugs, including tricyclic antidepressants (TCAs), cocaine, diphenhydramine, citalopram, some antiarrhythmics, and others. Benefits of sodium bicarbonate may be related to an increased sodium concentration and/or a change in pH. The best evidence of effectiveness of sodium bicarbonate is for TCA-induced sodium channel blockade. Further research is needed to determine the most effective dosing regimen (106257,106258).
• Gingivitis. Brushing the teeth with sodium bicarbonate seems to be beneficial for gingivitis. Details: A meta-analysis of seven clinical trials in patients with mild to moderate gingivitis shows that using a 67% bicarbonate toothpaste twice daily for 3-24 weeks has a small beneficial effect on gingivitis, plaque, and bleeding when compared with placebo toothpaste (109692), One specific toothpaste (Parodontax Daily Toothpaste, GlaxoSmithKline) was used in some of the individual studies (98210,109692).

POSSIBLY INEFFECTIVE

• Cardiac arrest. Intravenous sodium bicarbonate does not seem to improve survival in children or adults with an out-of-hospital cardiac arrest. Details: A meta-analysis of randomized controlled trials and observational research shows that sodium bicarbonate administration during cardiopulmonary resuscitation in adults does not improve the survival rate until hospital discharge in patients that had an out-of-hospital cardiac arrest when compared with no sodium bicarbonate administration. There was also no difference in the rate of return to spontaneous circulation (ROSC), with some preliminary evidence suggesting that the use of sodium bicarbonate actually reduces the incidence of sustained ROSC and the incidence of good neurological outcome at discharge (106247). There is also concern regarding the use of sodium bicarbonate in pediatric cardiac arrest. American Heart Association Pediatric Life Support (PLS) guidelines state that sodium bicarbonate administration is not recommended for routine management of cardiac arrest in pediatric patients (106254). A meta-analysis of seven observational studies has found that intravenous administration of sodium bicarbonate during pediatric resuscitation actually led to a moderate reduction in the rate of survival until hospital discharge (106246). The effect of sodium bicarbonate administration on neurological outcomes in adults with an out-of-hospital cardiac arrest has also been evaluated. Observational research in a French dataset has found that sodium bicarbonate administration is not associated with neurological outcome after 30 days. However, in North America, sodium bicarbonate administration is associated with 55% decreased odds of having a favorable functional outcome and a 41% reduction in survival (109693).
• Ischemia-reperfusion injury. Intravenous sodium bicarbonate does not seem to prevent ischemia-reperfusion kidney injury in patients undergoing cardiac surgery. Details: A meta-analysis of clinical research shows that administering intravenous sodium bicarbonate does not prevent ischemia-reperfusion kidney injury when compared with placebo in adults undergoing cardiac surgery (97733).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Although there is interest in using topical sodium bicarbonate for eczema, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Bowel preparation. Sodium bicarbonate is an ingredient in some approved medications for bowel cleansing. However, there is insufficient reliable information about the clinical effects of sodium bicarbonate alone for this use.
• Burns. Although there is interest in using topical sodium bicarbonate for burns, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Cancer. Although there is interest in using intratumoral sodium bicarbonate for cancer, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Chronic kidney disease (CKD). It is unclear if oral sodium bicarbonate is beneficial for CKD. Details: Preliminary clinical studies in adults with stage 3-5 CKD and low serum bicarbonate levels show that taking oral sodium bicarbonate 5.95-11.9 mEq three times daily or 0.4 mEq/kg daily for 12 months increases serum bicarbonate levels, but does not improve kidney function, quality of life, bone mineral density, or physical functioning scores, when compared with placebo (104845,104851). Some clinical research in adults undergoing continuous ambulatory peritoneal dialysis shows that adding oral sodium bicarbonate 900 mg three times daily for 12 months to prescription dialysis improves nutritional status and reduces the duration of hospitalization, but not number of hospitalizations, when compared with placebo (29940). One preliminary clinical trial shows that taking sodium bicarbonate, titrating up to an average of 3.7 grams daily in two divided doses, for 12 weeks reduces the frequency of hyperkalemia from 11% of measurements at baseline to 4%. Also, pre-dialysis bicarbonate levels were increased by 2.12 mmol/L (109689). However, the target bicarbonate level of 22 mmol/L was not consistently achieved and there was no benefit in lean body mass, muscle strength, or electrocardiogram changes (109689). Also, other clinical research in patients with metabolic acidosis prior to dialysis shows that administering dialysate bicarbonate 40 mEq/L with or without oral sodium bicarbonate 1 mEq/kg daily in three divided doses for 16 weeks does not improve nutritional parameters when compared with dialysate bicarbonate 35 mEq/L alone (29939).
• Constipation. Although there is interest in using oral and topical sodium bicarbonate for constipation, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Contrast induced nephropathy. It is unclear if intravenous sodium bicarbonate is beneficial for contrast induced nephropathy prevention. Details: Clinical trials evaluating the use of intravenous sodium bicarbonate report conflicting results and utilize heterogeneous doses, comparators, and concomitant therapies. Meta-analyses of clinical research show that intravenous sodium bicarbonate (sodium concentration 80-154 mEq/L) 1 mL/kg/hr for up to 12 hours or 3 mL/kg/hr for 1 hour prior to cardiac angiography, followed by 1 mL/kg/hour for 6-12 hours following cardiac angiography, reduces the risk of contrast induced nephropathy when compared to hydration with normal saline (25714,25715,25717,25718,25721,25754,97036). However, when only studies that compared the effects of sodium bicarbonate plus N-acetylcysteine to normal saline plus N-acetylcysteine are considered, the favorable effect of sodium bicarbonate was less significant or not significantly different (25715,25717), suggesting that N-acetylcysteine may have been responsible for the enhanced effectiveness shown in other studies. Additionally, most of the analyses note that significant heterogeneity exists among the published studies. When only large, higher methodological quality, randomized controlled trials are considered, sodium bicarbonate does not appear to reduce the risk of contrast induced nephropathy when compared to hydration with sodium chloride (25716,25721,97036). Clinical research shows that sodium bicarbonate does not appear to reduce the risk of congestive heart failure, the need for renal replacement therapy, or mortality when compared with normal saline (25711,25713,25714,25717,25718,25721,25754). Preliminary clinical research in patients with stage 3 chronic kidney disease also shows that no hydration is similar to hydration with 250 mL of sodium bicarbonate (sodium concentration 170 mEq/L). Follow up after 2-5 days and 7-14 days shows that the relative increase in serum creatinine with no hydration is non-inferior to sodium bicarbonate. However, the volume and concentration of sodium bicarbonate used in this trial was lower than many trials that previously demonstrated benefits (104846). Finally, a meta-analysis of the available literature suggests that xanthine and statins are superior to both sodium bicarbonate and normal saline for the treatment of contrast induced nephropathy (97036).
• Dental plaque. It is unclear if brushing the teeth or rinsing the mouth with sodium bicarbonate is beneficial for dental plaque reduction. Details: A meta-analysis of clinical research shows that brushing teeth one time with 1.5 grams of toothpaste containing sodium bicarbonate 20% to 65% removes plaque better than brushing teeth with toothpaste containing triclosan/copolymer or fluoride/silica and no sodium bicarbonate, particularly for teeth that are difficult to reach with a toothbrush (25708). Products assessed in the analysis included Arm & Hammer Dental Care, Arm & Hammer Advanced White Brilliant Sparkle, Arm & Hammer Advance White Baking Soda and Peroxide, and Arm & Hammer Liquid Gel (Church & Dwight Co. Inc.). However, the meta-analysis is limited by the fact that most studies were only single-brushing crossover comparisons. Therefore, it is not clear if sodium bicarbonate-containing toothpastes are significantly better than toothpastes that do not contain sodium bicarbonate when used long-term. Additionally, some limited research suggests that sodium bicarbonate seems to work as well as fluoride in toothpaste for removing dental plaque. One small clinical study shows that brushing teeth once with toothpaste containing sodium bicarbonate 20% to 67% is no different for reducing plaque than brushing teeth with control toothpaste containing 0.312% fluoride (101264). Preliminary clinical research also shows that using an oral rinse (Periogen) containing sodium bicarbonate, sodium fluoride, and multiple other ingredients for 60 seconds, twice daily for 3 days, decreases dental plaque and bleeding by a small amount when compared with baseline in healthy patients who did not brush their teeth during the study (97731).
• Earwax. It is unclear if ear drops containing sodium bicarbonate are beneficial for removing earwax. Details: Preliminary clinical research shows that treatment with sodium bicarbonate solution four drops twice daily for 5 days prior to irrigation improves earwax clearance better than no treatment and similar to Cerumol ear drops. The percentage of ears completely cleared by irrigation after treatment with Cerumol, sodium bicarbonate, and no treatment is 22%, 20%, and 5%, respectively (29936). Other clinical research shows that administering 10% sodium bicarbonate solution four drops daily for 14 days is similarly effective to 2.5% acetic acid solution for reducing the degree of earwax in children and adults with occlusive earwax (29937). However, treatment with sodium bicarbonate solution prior to irrigation may make syringing more difficult when compared to other methods. Some clinical research shows that administering Cerumol ear drops once daily for 3 days prior to syringing makes syringing easier when compared to administering sodium bicarbonate for the same treatment duration in elderly patients (29938).
• Gastroesophageal reflux disease (GERD). Sodium bicarbonate is an ingredient in some approved medications for GERD. However, there is insufficient reliable information about the clinical effects of sodium bicarbonate alone for this use.
• Hyperkalemia. Although there is interest in using oral and intravenous sodium bicarbonate for hyperkalemia, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Infertility. Although there is interest in using intravaginal sodium bicarbonate for infertility, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Insect bite. Although there is interest in using topical sodium bicarbonate for insect bite treatment, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Jellyfish stings. It is unclear if topical sodium bicarbonate is beneficial for jellyfish stings. Details: Preliminary clinical research shows that topical application of a sodium bicarbonate 50% slurry on gauze, replaced every 2 minutes for 30 minutes, does not reduce pain associated with jellyfish stings when compared with placebo. However, application of the slurry reduces overall redness (97730).
• Kidney stones (nephrolithiasis). Although there is interest in using oral sodium bicarbonate for kidney stones, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Muscle Strength. It is unclear if oral sodium bicarbonate is beneficial for muscle strength. Details: A meta-analysis of small clinical studies in healthy adults shows that taking sodium bicarbonate 300-400 mg/kg 1-2 hours before exercise does not improve mean muscle strength when compared with placebo (104852).
• Neonatal resuscitation. It is unclear if intravenous sodium bicarbonate improves outcomes in neonates requiring resuscitation. Details: Preliminary clinical research in asphyxiated newborns still requiring positive pressure ventilation at 5 minutes of life shows that intravenous sodium bicarbonate 4 mL/kg (1.8 mEq/kg) for 3-5 minutes does not improve survival or reduce the risk of neurological abnormality, encephalopathy, cerebral edema, need for inotropic support, or risk of intraventricular hemorrhage when compared with 5% dextrose (25692).
• Oral mucositis. It is unclear if rinsing the mouth with sodium bicarbonate is beneficial for chemotherapy-associated oral mucositis. Details: Clinical research in patients with chemotherapy-induced oral mucositis shows that using 7.5 mL of a mouthwash containing sodium bicarbonate 5% for 3 weeks has a moderate to large beneficial effect on the severity of mucositis and quality of life when compared with placebo. The mouthwash was swished for two, two-minute sessions separated by 15 minutes, repeated every 8 hours (109690).
• Organophosphorus pesticide poisoning. Although there is interest in using intravenous sodium bicarbonate for organophosphorus pesticide poisoning, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Peptic ulcers. Sodium bicarbonate is an ingredient in some approved medications for peptic ulcers. However, there is insufficient reliable information about the clinical effects of sodium bicarbonate alone for this use.
• Poison oak and poison ivy dermatitis. Although there is interest in using topical sodium bicarbonate for poison oak and poison ivy dermatitis, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Pruritus. Although there is interest in using topical sodium bicarbonate for pruritus, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Psoriasis. It is unclear if topical sodium bicarbonate is beneficial for psoriasis. Details: In patients with mild to moderate stable plaque psoriasis, a small clinical trial shows that topical sodium bicarbonate 30% does not improve symptoms of psoriasis when compared with a lanette wax vehicle only (106256).
• Rhabdomyolysis. Although there is interest in using intravenous sodium bicarbonate for preventing rhabdomyolysis-induced kidney injury, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Salicylate intolerance. Although there is interest in using intravenous sodium bicarbonate for salicylate intolerance, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Tooth discoloration. It is unclear if brushing the teeth with sodium bicarbonate is beneficial for tooth discoloration. Details: Preliminary clinical research shows that using a specific toothpaste containing 35% sodium bicarbonate (Arm & Hammer Truly Radiant Toothpaste, Church & Dwight Co. Inc.) for 2 minutes twice daily for 6 weeks reduces tooth staining by approximately 45% when compared to baseline. This product was more beneficial than a non-whitening toothpaste control, as well as a positive control that reduced staining by approximately 38% over baseline (97736). However, preliminary clinical research shows that using a toothpaste containing sodium bicarbonate 67% (Corsodyl Daily Gum and Toothpaste, GSK Consumer Healthcare) for one minute twice daily for 6 weeks does not reduce staining associated with use of a chlorhexidine 0.2% mouthwash when compared with a control toothpaste without sodium bicarbonate (97727).
• Urinary tract infections (UTIs). Although there is interest in using oral sodium bicarbonate for UTIs, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition.
• Ventilator-associated pneumonia (VAP). It is unclear if rinsing the mouth with sodium bicarbonate reduces the risk of VAP. Details: Preliminary clinical research in adults who have been mechanically ventilated for at least 4 days shows that using an oral rinse containing sodium bicarbonate 0.13 grams in 20 mL every 2 hours, in conjunction with tooth brushing three times daily, does not reduce the risk of VAP when compared with sterile water and tooth brushing (97737).
• Wound healing. Although there is interest in using topical sodium bicarbonate for wound healing, there is insufficient reliable information about the clinical effects of sodium bicarbonate for this condition. More evidence is needed to rate sodium bicarbonate for these uses.

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POSSIBLY SAFE ...when used orally and appropriately. NADH has been safely used at doses up to 10 mg daily for up to 12 weeks and 20 mg daily for up to 8 weeks (8267,8275,93686,107448).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY UNSAFE ...when used orally in excessive amounts. Over 20 cases of stomach rupture have been reported for patients who used sodium bicarbonate to relieve stomach discomfort after eating large meals (29414,29415,29416,29962,90913). In some of these cases, it is believed that the patients consumed dry sodium bicarbonate or a sodium bicarbonate suspension rather than a completely dissolved sodium bicarbonate solution. Ingestion of undissolved or partially undissolved sodium bicarbonate is believed to produce excess carbon dioxide and corresponding gastric dilation, leading to stomach rupture (90913). There is also concern that excessive or prolonged use of oral sodium bicarbonate may cause metabolic alkalosis characterized by hypokalemia, hypochloremia, and hypernatremia (25733,29962,90913). There is insufficient reliable information available about the safety of sodium bicarbonate when used topically.

CHILDREN: POSSIBLY SAFE
when used intravenously and appropriately with proper medical supervision. Intravenous sodium bicarbonate solutions are approved by the US Food and Drug Administration (FDA) to be used in infants and children (13309).

CHILDREN: POSSIBLY UNSAFE
when used topically. At least two cases of hypernatremia resulting from topical application of sodium bicarbonate (baking soda) have been reported (29962,90914). There is insufficient reliable information available about the safety of sodium bicarbonate when used orally; avoid using unless advised by a physician.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally or intravenously during pregnancy. There is concern that sodium bicarbonate may increase the risk of metabolic alkalosis or fluid retention when used orally during pregnancy (90915). There is insufficient reliable information available about the safety of oral or intravenous sodium bicarbonate when used in medicinal amounts during lactation.

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AMINOGLYCOSIDE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk for hypokalemia in patients receiving aminoglycosides.  Details Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, when administered intravenously, the most common complication of sodium bicarbonate is hypokalemia (25709). Nephrotoxicity caused by aminoglycosides may lead to increased urinary losses of various electrolytes, including potassium (9519).

AMPHOTERICIN-B (Abelcet, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk for hypokalemia in patients receiving amphotericin B.  Details Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, when administered intravenously, the most common complication of sodium bicarbonate is hypokalemia (25709). Amphotericin B increases urinary potassium losses due to toxic effects on renal tubular epithelium. Hypokalemia can occur in up to 50% of patients (9519).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, sodium bicarbonate may reduce the levels and clinical effects of aspirin.  Details In humans, oral or intravenous administration of sodium bicarbonate increases salicylate elimination. Although the exact mechanism of this effect is not clear, some researchers hypothesize that sodium bicarbonate increases urinary pH, which increases salicylate ionization and subsequent excretion by the kidneys. In patients with urine pH of about 5.5, renal clearance of salicylate is approximately 55 mL/min. When urine pH is increased with oral sodium bicarbonate to about 7.5, renal clearance of salicylate increases to approximately 100 mL/min. Similarly, urine alkalinization with sodium bicarbonate increases the mean total body clearance of salicylate by approximately 60% compared with urine acidification (29410,29411).

BETA-ADRENERGIC AGONISTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk for hypokalemia in patients taking beta-adrenergic agonists.  Details Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, the most common adverse effect of intravenous sodium bicarbonate is hypokalemia (25709). Oral, parenteral, or inhaled beta-adrenergic agonists can reduce serum potassium levels, especially during acute use of high doses (6217,7001,8880,8881,8882,8883,8884,8885,8886,8889)(8890,9534,9599).

CEFPODOXIME PROXETIL (Vantin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, sodium bicarbonate might reduce the levels and clinical effects of cefpodoxime.  Details Cefpodoxime proxetil is an oral prodrug that is de-esterified in the intestine to the active drug cefpodoxime. Drugs or supplements that increase gastric pH can inhibit the activation of cefpodoxime proxetil and reduce the peak plasma concentrations of cefpodoxime. In humans, taking sodium bicarbonate 12.6 grams orally along with cefpodoxime proxetil 200 mg reduces peak plasma concentrations and area under the plasma concentration-time curve (AUC) of cefpodoxime by 35% to 50% (25740).

CHLORPROPAMIDE (Diabinese) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, sodium bicarbonate might reduce the levels and clinical effects of chlorpropamide.  Details The elimination of chlorpropamide by the kidneys depends strongly on urine pH. At a pH of 5, the renal clearance of chlorpropamide ranges from 0.5 to 3 mL/hr. At a pH of 8, renal clearance of chlorpropamide ranges from 500 to 1000 mL/hr. When taken in combination with oral sodium bicarbonate, the elimination half-life of chlorpropamide is shortened from 49.7 to 12.8 hours and urinary excretion of chlorpropamide is increased four-fold (25741).

CISPLATIN (Platinol-AQ) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk of hypokalemia in patients receiving cisplatin.  Details Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, the most common complication of intravenous sodium bicarbonate is hypokalemia (25709). Cisplatin can cause renal tubular damage, with increased losses of electrolytes including potassium (15509,15510,15511).

CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk of hypokalemia in patients taking corticosteroids.  Details Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, the most common intravenous complication of sodium bicarbonate is hypokalemia (25709). Some glucocorticoids (corticosteroids) can also cause hypokalemia by causing sodium retention, resulting in compensatory renal potassium excretion. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).

LOOP DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk of hypokalemia in patients taking loop diuretics.  Details Loop diuretics increase urinary potassium excretion (4412,4425,4449). Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, the most common complication of intravenous sodium bicarbonate is hypokalemia (25709).

METHYLXANTHINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk of hypokalemia in patients taking methylxanthines.  Details Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, the most common complication of intravenous sodium bicarbonate is hypokalemia (25709). Theophylline and related drugs can reduce serum potassium levels, possibly by increasing intracellular uptake of potassium. Hypokalemia is most likely to occur after acute overdose of these drugs (17). However, reduced potassium levels can occur with therapeutic doses, and the incidence and degree of hypokalemia increases with increasing serum theophylline levels (9534,9537,9538,9539).

PSEUDOEPHEDRINE (Sudafed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, sodium bicarbonate may increase levels and adverse effects of pseudoephedrine.  Details In humans, intravenous or oral administration of sodium bicarbonate can increase urinary pH. Clinical evidence shows that urine alkalinization increases the serum elimination half-life of pseudoephedrine by approximately 10-fold (29412). In one patient with persistently alkaline urine, treatment with pseudoephedrine resulted in hallucinations and personality changes (29412).

SODIUM-CONTAINING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related adverse effects.  Details The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium bicarbonate, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

STIMULANT LAXATIVES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk of hypokalemia in patients taking stimulant laxatives.  Details Long-term use of stimulant laxatives, or acute use of high doses (e.g., in bowel-cleansing regimens), can result in potassium loss and hypokalemia (4411,4412,4425). Orally, use of excessive sodium bicarbonate (such as intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, the most common complication of intravenous sodium bicarbonate is hypokalemia (25709).

THIAZIDE DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sodium bicarbonate may increase the risk of hypokalemia in patients taking thiazide diuretics.  Details Thiazide diuretics increase urinary potassium excretion (4412,4425,4449). Orally, use of excessive sodium bicarbonate (such as the intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with cases of hypokalemia (25733). Furthermore, the most common complication of intravenous sodium bicarbonate is hypokalemia (25709).

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General ...Orally, NADH seems to be well tolerated. No adverse effects have been reported in clinical research.

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General ...Orally, sodium bicarbonate is generally well tolerated when used in over-the-counter antacid products. However, it is possibly unsafe when used in excessive amounts. Intravenously, sodium bicarbonate is generally well tolerated when used appropriately with proper medical supervision. Topically, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, diarrhea, flatulence, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Metabolic alkalosis and stomach rupture.
Intravenously: Alkalotic tetany, hypernatremia, hypocalcemia, hypokalemia, and metabolic alkalosis.

Cardiovascular ...Orally, sodium bicarbonate has been reported to cause increased blood pressure (109689).

Gastrointestinal ...Orally, sodium bicarbonate may cause mild adverse effects including gastrointestinal disturbance such as bloating, nausea, vomiting, and abdominal pain (25706,106250). The severity of these effects appears to increase with dose (104850). When taken in large amounts (300 mg/kg as a single dose, 4 ounces over a 24-hour time period, or 10-12 ounces over 5 days), sodium bicarbonate can cause diarrhea, nausea, vomiting, bloating, flatulence, and abdominal pain (29962,104853,104850). Gastrointestinal side effects during exercise can be reduced when single doses of 200-300 mg/kg are taken 3 hours before with a high-carbohydrate meal (106250). Taking enteric-coated or delayed-release formulations may also reduce the incidence and severity of mild gastrointestinal symptoms (104853,106250), but enteric-coated formulations may also reduce overall absorption of bicarbonate (104853).
Sodium bicarbonate antacids may cause serious gastrointestinal effects, including stomach rupture, if taken orally as a partially dissolved slurry rather than a solution, especially if taken when overly full from food or drink (25735,25736,29414,29415,29416,90913).

Hematologic ...In patients with normal kidney function, appropriate use of oral sodium bicarbonate may not cause significant alkalosis, although it may increase loss of sodium, chloride, potassium, and volume due to diuresis (25733). However, excessive use or chronic oral intake of sodium bicarbonate may induce metabolic alkalosis characterized by levels of sodium bicarbonate ≥40 mEq/L, hypokalemia, hypochloremia, and hypernatremia (25733,29962,106255). When administered intravenously, the most common complication of sodium bicarbonate is hypokalemia (25709). Hypocalcemia or hypernatremia may also occur, although these effects are less common and typically associated with overaggressive therapy (25709,106255).
At least two cases of hypernatremia resulting from topical application of sodium bicarbonate (baking soda) have been reported (29962,90914).

Musculoskeletal ...Metabolic alkalosis induced by sodium bicarbonate has reportedly been associated with tetany that results from hypocalcemia; however, this condition is rare (25709).

Neurologic/CNS ...Orally, concomitant use of excessive sodium bicarbonate (intake of "tablespoons" of sodium bicarbonate daily or up to one box of baking soda weekly) has been associated with at least two cases of hypercalcemia-induced metabolic alkalosis, characterized by dizziness, headache, and loss of consciousness with shivering (25733). Rare symptoms include drowsiness, lethargy, seizures, and coma (106255). Sodium bicarbonate may also cause metabolic alkalosis and the associated symptoms when administered intravenously (13309). However, these effects are typically associated with therapy that is overaggressive.

Ocular/Otic ...At least three cases of otitis externa have been reported following the use of eardrops containing sodium bicarbonate (25696).

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