Liposomal Glutathione With Lemon Mint [Discontinued] by Quicksilver Scientific

POSSIBLY EFFECTIVE

• Cisplatin-induced neurotoxicity. Intravenous glutathione seems to reduce neurotoxicity from cisplatin. Details: Clinical studies in cancer patients receiving cisplatin shows that administering glutathione 1.5 grams/m2 by intravenous injection over 15 minutes seems to help prevent neurotoxicity and other toxicities from cisplatin when compared with control. Glutathione may also increase the highest dose of cisplatin that patients are able to tolerate (5373,5374,5377,5378,5380). In one study, this same dose of intravenous glutathione was administered, along with intramuscular glutathione 600 mg on days 2-5 (5374).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there is interest in using oral glutathione for aging, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Alcohol use disorder. Although there is interest in using oral glutathione for alcohol use disorder, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Athletic performance. Oral glutathione has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in young, resistance-trained males shows that taking glutathione (Setria, Kyowa Hakko Bio) 200 mg in combination with L-citrulline 2 grams daily for 8 weeks in conjunction with resistance training has no effect on muscle strength, as measured by leg and bench presses, when compared with L-citrulline alone or with placebo (97394). The trial shows the increase in lean body mass with training to be significantly higher with glutathione and L-citrulline compared with placebo at 4 weeks. However, by 8 weeks of training lean body mass is not different between supplementation and placebo. An additional small, cross-over trial in young, endurance-trained males shows that taking glutathione 200 mg in combination with L-citrulline 2 grams (Setria Performance Blend, Kyowa Hakko Bio) daily for 8 days does not improve high speed running performance, as measured by time to exhaustion, when compared with placebo (112285).
• Angioplasty. It is unclear if intravenous glutathione is beneficial in patients recovering from angioplasty following myocardial infarction. Details: A small clinical trial in Italian adults undergoing primary percutaneous coronary intervention (PCI) for recent ST-elevation myocardial infarction (STEMI) shows that intravenous infusion of glutathione sodium salt 2500 mg/25 mL over 10 minutes before angioplasty and at 24, 48 and 72 hours after angioplasty reduces length of hospital stay by around 2 days; reduces markers of oxidative stress, inflammation, and cardiomyocyte damage; and improves measures of left ventricular function at 6-month's follow-up when compared with placebo (111417,111418).
• Alzheimer disease. Although there is interest in using oral glutathione for Alzheimer disease, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Cardiovascular disease (CVD). Although there is interest in using oral glutathione for preventing CVD, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Cataracts. Although there is interest in using oral glutathione for cataracts, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral glutathione for CFS, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Cirrhosis. It is unclear if oral glutathione is beneficial for improving cirrhosis severity. Details: A small clinical study in patients with cirrhosis shows that taking glutathione 500 mg daily with or without vitamin B6 50 mg daily for 12 weeks does not affect disease severity or reduce oxidative stress when compared with placebo (104392). These findings are limited because the study might not have been powered to detect a difference between groups, as 21 of the 61 participants were lost to follow-up.
• Cognitive function. Oral glutathione has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small cross-over trial in healthy adults shows that taking a product providing 20 mg/day of glutathione as part of a combination product containing probiotics (L. helveticus, Lactiplantibacillus plantarum, Bifidobacterium longum), inulin, zinc, potassium, magnesium and lactoferrin (Puraflor, GSK Consumer Healthcare) for 4 weeks does not affect cognitive performance during acute stress when compared with placebo (110923).
• Contrast induced nephropathy. It is unclear if intravenous glutathione is beneficial for preventing contrast induced nephropathy. Details: A small, non-blinded clinical study in patients aged 65 or older with diabetes undergoing percutaneous coronary intervention (PCI) shows that intravenous reduced glutathione 180 mg daily for 4 days, starting 6 hours prior to PCI, in conjunction with saline hydration, does not reduce the rate of contrast induced nephropathy when compared with saline hydration alone. Saline hydration was administered at a rate of 1 mL/kg/hr, starting 6 hours prior to PCI and continuing for 12 hours after PCI (107477). However, this study may have been inadequately powered to detect a difference between groups.
• Cystic fibrosis. It is unclear if oral glutathione is beneficial in children with this condition. Details: A small clinical study in children ages 2-10 years old with cystic fibrosis shows that taking glutathione powder 65 mg/kg daily in 3 divided doses for 6 months does not impact weight or inflammatory biomarkers when compared with placebo (104391).
• Glaucoma. Although there is interest in using oral glutathione for glaucoma, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Idiopathic interstitial pneumonia. Although there is interest in using inhaled glutathione for idiopathic pulmonary fibrosis, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral glutathione is beneficial in patients with NAFLD. Details: Preliminary clinical research shows that taking glutathione 300 mg daily for 4 months reduces alanine aminotransferase (ALT) levels by around 13% and triglyceride levels by around 16%, but has no impact on aspartate aminotransferase (AST) levels or liver stiffness, when compared with baseline in patients with NAFLD (97397). The validity of these findings is limited by the lack of a comparator group.
• Osteoarthritis. Although there is interest in using oral glutathione for osteoarthritis, there is insufficient reliable information about the clinical effects of glutathione for this condition.
• Parkinson disease. It is unclear if intranasal glutathione is beneficial for improving Parkinson disease symptoms. Details: A small clinical study in patients with Parkinson disease shows that taking glutathione intranasally 100-200 mg three times daily for 3 months has no effect on symptoms when compared with placebo (97398). More evidence is needed to rate glutathione for these uses.

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POSSIBLY EFFECTIVE

• Ulcerative colitis. Limited clinical research shows that taking phosphatidylcholine products may improve clinical and remission scores in adults with ulcerative colitis. Details: Clinical research suggests that taking slow-release, phosphatidylcholine-rich phospholipids (Sterpur P-30 Granulat, Stern-Lecithin and Soja GmbH) improves symptoms and remission rate in patients with ulcerative colitis (68839,93389,93390,105728). A pooled analysis of 3 small randomized clinical trials in adults with chronic, active, ulcerative colitis at a single site shows that taking this specific form of phosphatidylcholine 1-4 grams daily for 3 months increases the odds of achieving clinical remission by 9.7 times when compared with placebo. Overall, 49% of the patients taking phosphatidylcholine achieved clinical remission. Taking phosphatidylcholine also improved quality of life and clinical improvement scores. In one study, this product also decreased the need for steroids, resulting in complete withdrawal of steroid therapy without exacerbation of disease in 80% of patients (93390). However, most patients in these studies were not treated with other standard therapies for ulcerative colitis, such as immunosuppressants and aminosalicylic acids. Subgroup analyses by dose suggest that the effective dose of this product is at least 1 gram daily; however, taking 3-4 grams daily may be more effective (93389,105728). In patients not responsive to mesalamine, some preliminary clinical research suggests taking LT-02 (Lipid Therapeutics GmbH), a modified-release formula of phosphatidylcholine, 3.2 grams daily for 12 weeks, improves symptoms of ulcerative colitis. Overall disease activity was improved by 52%, compared with 33% in those taking placebo. The effects on remission rate and mucosal healing were unclear; however, response rates were increased from 60% in the placebo group to 83% in the phosphatidylcholine group. In an 8-week follow-up, relapse was also less likely in patients treated with this product (93387).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Topical phosphatidylcholine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a topical cream containing niacinamide and linoleic acid-rich phosphatidylcholine (4% niacinamide-phospholipidic; N-PHCL emulsion) once daily for 12 weeks improves skin hydration and reduce acne lesions and inflammation when compared with a 1% clindamycin cream or a carrier-only cream in patients 15 years and older with moderate acne (93388).
• Aging. Although there has been interest in using oral phosphatidylcholine for aging, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Alcohol-related liver disease. It is unclear if oral phosphatidylcholine is beneficial in patients with alcohol-related liver disease. Details: Preliminary clinical research in adults with acute alcoholic hepatitis shows that taking polyunsaturated phosphatidylcholine 6 grams orally daily for 24 months does not increase survival when compared with placebo (68843).
• Alzheimer disease. Although there has been interest in using oral phosphatidylcholine for Alzheimer disease, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Angina. Although there has been interest in using intravenous phosphatidylcholine for angina, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Anxiety. Although there has been interest in using oral phosphatidylcholine for anxiety, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Atherosclerosis. Although there has been interest in using intravenous phosphatidylcholine for atherosclerosis, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Atopic dermatitis (eczema). Although there has been interest in using oral phosphatidylcholine for atopic dermatitis, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Bipolar disorder. Although there has been interest in using oral phosphatidylcholine for bipolar disorder, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Dementia. It is unclear if oral phosphatidylcholine is beneficial in patients with dementia. Details: Population research in a sample of 1259 men in Finland suggests that high daily intake of phosphatidylcholine is associated with a 28% lower risk of developing dementia when compared with low daily intake, over a mean follow-up of about 22 years (103178).
• Fatty deposits. It is unclear if subcutaneous phosphatidylcholine is beneficial in patients with fatty deposits. Details: Very low quality clinical research shows that administering subcutaneous injections of phosphatidylcholine 125 mg-250 mg every 7-15 days can reduce localized fatty deposits on the chin, thigh, hips, abdomen, back, neck, and elsewhere, based on subjective visual assessments, when compared with baseline (15621,15625,15627). Improvements appear to last for 2-3 years or longer (15621,15627). In one study, phosphatidylcholine injections markedly or moderately reduce localized fatty deposits on the face in about 80% of patients for a period of up to 3 years based on subjective patient self-assessment (15621).
• Hepatic encephalopathy. It is unclear if oral phosphatidylcholine is beneficial in patients with hepatic encephalopathy. Details: Preliminary clinical research shows that taking polyunsaturated phosphatidylcholine 1050 mg daily for 6-8 weeks, either orally or through a nasogastric tube, does not improve recovery from encephalopathy compared with control in patients with acute or subacute liver failure. However, polyunsaturated phosphatidylcholine seems to reduce mortality compared to control in patients with subacute, but not acute, liver failure (68835).
• Hepatitis A. It is unclear if oral phosphatidylcholine is beneficial in patients with hepatitis A. Details: Preliminary clinical research shows that taking phosphatidylcholine 900 mg orally daily for 12 weeks does not seem to reduce serum bilirubin or liver enzyme levels in patients with hepatitis A when compared with no intervention (5225).
• Hepatitis B. It is unclear if oral phosphatidylcholine is beneficial in patients with hepatitis B. Details: Preliminary clinical research in adults undergoing interferon treatment for hepatitis B shows that taking phosphatidylcholine 1.8 grams orally daily for 24 weeks improves clinical response when compared with placebo (5226). Other preliminary clinical research in patients with chronic active hepatitis B shows that taking phosphatidylcholine 3 grams orally improves histological disease scores when compared with control (5224).
• Hepatitis C. Oral phosphatidylcholine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults undergoing interferon treatment for hepatitis C shows that taking phosphatidylcholine 1.8 grams orally daily for 24 weeks improves clinical response when compared with placebo (5226).
• Hypercholesterolemia. Although there has been interest in using intravenous phosphatidylcholine for hypercholesterolemia, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Hyperlipidemia. Although there has been interest in using oral phosphatidylcholine for hyperlipidemia, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Hyperlipoproteinemia. Oral phosphatidylcholine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking polyunsaturated phosphatidylcholine 1.8 grams daily for 28 days in combination with clofibrate does not significantly reduce total cholesterol, triglycerides, or phospholipids compared to clofibrate alone in patients with primary hyperlipoproteinemia of Fredrickson Types II or IV. However, taking the combination of polyunsaturated phosphatidylcholine plus clofibrate seems to significantly attenuate the relative increase in low-density lipoprotein (LDL) cholesterol when compared with clofibrate alone (68840).
• Infant development. It is unclear if oral phosphatidylcholine is beneficial for infant development. Details: Preliminary clinical research shows that taking phosphatidylcholine (PhosChol, Nutrasal) 5 grams daily, containing choline 750 mg daily, from 18 weeks' gestation to 90 days postpartum does not improve cognitive function in the infant at 10-12 months of age when compared with corn oil placebo (93386).
• Lipoma. It is unclear if subcutaneous phosphatidylcholine is beneficial in patients with lipoma. Details: An anecdotal report suggests that injecting a phosphatidylcholine solution directly into a lipoma can shrink the tumor by about 35%. However, in this report a major inflammatory reaction occurred, resulting in undesirable fibrotic changes to the tissue and eventual surgical excision of the lipoma (15622).
• Memory. It is unclear if oral phosphatidylcholine is beneficial for memory. Details: Preliminary clinical research shows that taking a single dose of phosphatidylcholine 25 grams (PC-55, TwinLab) orally can improve some measures of memory in healthy college students when compared with placebo (5228).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral phosphatidylcholine is beneficial in patients with NAFLD. Details: Preliminary clinical research shows that taking phosphatidylcholine 600 mg orally three times daily for 24 weeks qualitatively improves liver echogenicity and structure on an ultrasound scan, suggesting a reduction in hepatic steatosis, when compared to baseline. There is also a small decrease in liver function test values, but with considerable variability both at baseline and at 24 weeks (103176,103177). Preliminary clinical evidence also suggests that taking a combination of the milk thistle constituent silybin, phosphatidylcholine, and vitamin E (Realsil, Instituto Biochimico Italiano) orally twice daily for 12 months improves liver function tests (LFTs) and liver histology when compared with placebo in people with NAFLD (63244). It is unclear if this effect is due to phosphatidylcholine, other ingredients, or the combination.
• Periorbital fat pad herniation. It is unclear if subcutaneous phosphatidylcholine is beneficial in patients with periorbital fat pad herniation. Details: Preliminary clinical research shows that injecting phosphatidylcholine 20 mg subcutaneously every 2 weeks markedly reduces lower eyelid fat pads in people with bulging fat pads due to herniation when compared to baseline. In some people, benefits appeared to last for a period of 9 months to 2 years or longer (15623,15628).
• Peripheral arterial disease (PAD). Although there has been interest in using oral phosphatidylcholine for PAD, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Peritoneal dialysis. It is unclear if oral phosphatidylcholine is beneficial in patients with peritoneal dialysis. Details: Very preliminary clinical research shows that taking phosphatidylcholine 900 mg orally daily for 8 weeks does not improve ultrafiltration in peritoneal dialysis when compared to baseline (5222).
• Premenstrual syndrome (PMS). Although there has been interest in using oral phosphatidylcholine for PMS, there is insufficient reliable information about the clinical effects of phosphatidylcholine for this purpose.
• Tardive dyskinesia. It is unclear if oral phosphatidylcholine is beneficial in patients with tardive dyskinesia. Details: Preliminary clinical research taking phosphatidylcholine 30 grams orally daily for 6 weeks does not improve tardive dyskinesia symptoms when compared with placebo (5223). More evidence is needed to rate phosphatidylcholine for these uses.

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LIKELY EFFECTIVE

• Cystic fibrosis. Long-term nebulized hypertonic sodium chloride improves lung function and reduces pulmonary exacerbations in patients with cystic fibrosis. Details: Meta-analyses of clinical research in adults with cystic fibrosis show that, when taken along with a bronchodilator and other standard therapies, nebulized hypertonic sodium chloride in concentrations of 3% to 7%, up to 10 mL twice daily for 4 weeks, increases forced expiratory volume at one second (FEV1) when compared with isotonic saline (sodium chloride 0.9%) (26230,26230). This benefit was not seen at 48 weeks. Other clinical research in adults with cystic fibrosis shows that inhaling sodium chloride 7%, 4 mL twice daily for 48 weeks, does not improve FEV1 when compared with isotonic saline. However, chronic treatment with hypertonic saline does reduce the number of pulmonary exacerbations and increase the number of patients without pulmonary exacerbations when compared with isotonic saline (29402). It is not clear if this benefit occurs in children with cystic fibrosis. The Pulmonary Clinical Practice Guidelines Committee of the Cystic Fibrosis Foundation recommends that individuals with cystic fibrosis aged 6 years or older use nebulized hypertonic saline long-term to improve lung function, reduce the number of exacerbations, and improve quality of life (29403).

POSSIBLY EFFECTIVE

• Amphotericin B nephrotoxicity. Oral sodium chloride seems to prevent nephrotoxicity associated with use of amphotericin B. Details: Clinical research shows that administering oral or intravenous sodium chloride 150 mEq daily during treatment with amphotericin B can attenuate the rise in serum creatinine levels and preserve renal function when compared to treatment with amphotericin B alone (26226).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bipolar disorder. It is unclear if oral sodium is beneficial in preventing lithium level fluctuations in patients with bipolar disorder. Details: A moderate-sized open-label clinical study in adults with type I bipolar disorder receiving lithium carbonate shows that taking sodium chloride 1 gram daily for 12 weeks along with dietary salt restriction of 1 gram daily reduces the percentage of patients with lithium level fluctuations above 0.8 mEq/L, but does not significantly affect serum sodium, potassium, aldosterone, or creatinine levels when compared with controls who were not salt restricted, but were advised not to consume additional salt at the table (112909). However, the interpretation of these findings is limited by missing data in both groups.
• Canker sores. Although there is interest in using topical sodium chloride for canker sores, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Congestive heart failure. It is unclear if oral sodium is beneficial in patients with acute decompensated heart failure requiring decongestive therapy with diuretics. Details: A moderate-sized clinical study in adults hospitalized with acute decompensated heart failure requiring high-dose intravenous furosemide shows that taking sodium chloride 2 grams three times daily for up to 96 hours does not affect patient weight or serum creatinine levels when compared with placebo (112911). However, the clinical relevance of this study is unclear and it may have been inadequately powered to detect a difference between groups.
• Conjunctivitis. Although there is interest in using ophthalmic sodium chloride for conjunctivitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Hyponatremia. Although there is interest in using oral sodium chloride for hyponatremia, there is insufficient reliable information about the clinical effects of oral sodium chloride for this condition.
• Pharyngitis. Although there is interest in using topical sodium chloride for pharyngitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Prematurity. It is unclear if oral sodium is beneficial for premature infants. Details: Preliminary clinical research in infants born at less than 32 weeks' gestation shows that adding sodium 4 mEq/kg daily to enteral feedings, starting from the 7th day after birth and continuing through the 35th day, reduces the risk of developing hyponatremia and improves weight gain when compared with adding water (98180). A small, open-label clinical study in newborns less than 35 weeks gestation shows that high sodium intake, defined as an average of 0.25% sodium in maintenance fluids, for 48 hours on day 2 and 3 after birth results in less weight loss within the first 72 hours of life when compared with control, but does not improve mortality, length of hospital stay, or complications from prematurity (112908). However, interpretation of these findings is limited by varied concentrations of sodium as an intervention. More evidence is needed to rate sodium for these uses.

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POSSIBLY SAFE ...when used orally in doses up to 500 mg daily for up to 2 months (5361,5362,97394,97396,97399,104392). ...when used by inhalation in doses of 600 mg twice daily for up to 3 days (5367,5368,5369). ...when used intramuscularly (5374,5375,5384). ...when used as an intravenous injection (5344,5354,5357,5358,5359,5360,5373,5374,5377,5378,5380).

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

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POSSIBLY SAFE ...when used orally and appropriately. Large doses up to 30 grams per day for 6 weeks (5223) and smaller doses of up to 6 grams daily for up to 24 months have been well tolerated (68839,68843,105728). ...when used subcutaneously and appropriately, short-term. Some research suggests that subcutaneous injections of 0.2 mL to 5 mL of a 5% phosphatidylcholine solution do not cause significant serious adverse effects when doses are administered up to five times and spaced apart by 2-4 weeks (15621,15623,15624,15625). ...when used topically as an emulsion also containing niacinamide for up to 12 weeks (93388).

PREGNANCY: POSSIBLY SAFE
when used orally from 18 weeks of gestation at doses of up to 5 grams daily (93386)

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).

POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310). Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses. Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).

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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.  Details High intake of dietary sodium can increase systolic and diastolic blood pressure (26222). Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease (26223).

CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.  Details Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Altering dietary intake of sodium might alter the levels and clinical effects of lithium.  Details High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

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 complications.  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 supplements or high-sodium diets, 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.

TOLVAPTAN (Samsca) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.  Details Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

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General ...Glutathione seems to be well tolerated; however, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Inhaled: Bronchoconstriction and shortness of breath.

Dermatologic ...Topically, glutathione has resulted in an intolerable rash and irritability in five children (90637).

Pulmonary/Respiratory ...Inhaled (nebulized) glutathione can cause airway narrowing and bronchoconstriction resulting in shortness of breath and cough in patients with asthma (5372).

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General ...Phosphatidylcholine is generally well tolerated when used orally, subcutaneously, or topically.
Most Common Adverse Effects:
Orally: Altered taste, bloating, diarrhea, itching, nausea, sweating, vomiting.
Subcutaneously: Bruising, burning, edema, erythema, hematoma, itching, pain at the injection site.
Serious Adverse Effects (Rare):
Subcutaneously: Lipoma.

Dermatologic ...When taken orally, phosphatidylcholine may increase sweating (5229) and itching (63244). When given subcutaneously, phosphatidylcholine can cause pain, burning, itching, tenderness to touch, bruising, edema, and erythema at the injection site. The pain, itching and erythema usually resolve within 2 days of treatment; however localized tenderness can last longer (15623,15624,15626,15627,15628). Edema and bruising usually resolve within 10 days of treatment (15621,15623,15625). Some people can also develop nodules or hematoma at the injection site. This usually resolves within 30 days (15627).

Gastrointestinal ...Ingesting large amounts of phosphatidylcholine (30 grams per day) can cause gastrointestinal upset and diarrhea (5223). However, bloating, diarrhea, altered taste, nausea, and vomiting have been reported with smaller doses (63244,68843,93389,93390,105728). Although moderate subcutaneous doses do not usually cause systemic side effects, high doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624).

Musculoskeletal ...Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissue changes (15622).

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General ...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level. Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.

Cardiovascular ...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263). A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).

Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).

Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).

Musculoskeletal ...Observational research has found that low sodium levels can increase the risk for osteoporosis. One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).

Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).

Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).

Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).

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