Mangosteen by EB Earth's Bounty

POSSIBLY EFFECTIVE

• Periodontitis. Oral and topical mangosteen may modestly improve gum health. Details: A small clinical study in adults with chronic periodontitis shows that applying a gel containing mangosteen pericarp 4% to the periodontal pocket following scaling and root planing procedures improves pocket depth, clinical attachment, and bleeding by 56% to 63%, compared with a 33% to 42% improvement with placebo (97875). Another small clinical study in similar patients shows that applying mangosteen 4% gel to the periodontal pocket following scaling and root planning improves pocket depth and clinical attachment when compared with placebo. However, plaque and bleeding indices were not compared between groups (110126). A clinical study in patients with generalized or localized gingivitis or stage I periodontitis shows that taking 194 mg of a product containing mangosteen and propolis orally improves the modified gingival index by 31% or 40% at weeks 4 or 8, respectively, compared with 16% or 25% in those receiving placebo. No changes in probing depth, clinical attachment, plaque index, bleeding, or gingival recession were observed (106789). It is unclear if these effects are due to mangosteen, propolis, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral mangosteen is beneficial for patients with Alzheimer disease. Details: A small clinical study in adults with Alzheimer disease in Thailand shows that treatment with oral mangosteen pericarp extract, provided either as 220-280 mg daily for 24 weeks, or as 220-280 mg daily for 12 weeks followed by 440-560 mg daily for 12 weeks, does not consistently improve cognitive function scores to a clinically significant extent when compared with placebo. This study assessed cognitive function on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Thai Mental State Examination (110127). However, the validity of this study is limited by poor methodology, including inadequate power and blinding.
• Androgenic alopecia. Mangosteen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical trial in males and females with androgenic and diffuse alopecia shows that applying a hair lotion containing fermented mangosteen 2%, fermented papaya 2%, and caffeine 0.5% to the scalp daily plus use of a shampoo containing fermented mangosteen 0.5% and fermented papaya 0.5% 3 times weekly for 14 weeks improves hair shaft and root quality, hair diameter, and the density and percentage of thick hairs compared to baseline (111719). It is unclear if these effects are due to fermented mangosteen, other ingredients, or the combination.
• Atopic dermatitis (eczema). Although there has been interest in using topical mangosteen for eczema, there is insufficient reliable information about the clinical effects of mangosteen for this purpose.
• Muscle fatigue. It is unclear if oral mangosteen is beneficial in preventing muscle fatigue during physical activity. Details: A very small clinical study in healthy, physically active adults shows that drinking 250 mL of a specific mangosteen juice product (Lord Duke Biotechnology Corporation) containing mangosteen, pomegranate, acerola, white grape, strawberry, passion fruit, and tamarind, 1 hour prior to physical activity, does not improve time to exhaustion when compared to the juice product without mangosteen (92805).
• Muscle strength. Oral mangosteen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in young, resistance-trained males shows that taking a combination product (CinDura, Laila Nutraceuticals) containing mangosteen fruit rind extract and Indian cassia leaf extract 400 mg twice daily for 42 days increases muscle strength and endurance when compared with placebo. Single bench and leg presses improved by approximately 23.5 kg and 29.3 kg, respectively, compared with 3.4 kg and 5.2 kg, respectively, in those taking placebo. Also, the number of leg extension repetitions increased by 6.5, compared to an increase of 2 with placebo (101079). It is not clear if these benefits are due to mangosteen, Indian cassia, or the combination.
• Obesity. Oral mangosteen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults who were overweight shows that taking a specific combination product containing a mixture of mangosteen and Sphaeranthus indicus (Meratrim, Laila Nutraceuticals) 400 mg twice daily for 16 weeks results in weight loss of 6.7%, compared with weight loss of 1.4% with placebo (97876). In adults with obesity, taking the same dose of this product for 8 weeks results in an additional reduction in body weight of 4.6% when compared with placebo (97878,97879). This product also seems to improve body mass index (BMI), waist and hip measurements, and blood lipids in some patients (97876,97878,97879). It is not clear if these benefits are due to mangosteen, Sphaeranthus indicus, or the combination.
• Osteoarthritis. Topical mangosteen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large, single-blind clinical study in adults with knee osteoarthritis causing moderate pain shows that applying a specific cream (TMP-4) containing extracts of mangosteen peel, sesame seed, soybean, and gotu kola leaf four times daily for 4 weeks provides similar improvement in pain scores when compared with diclofenac 1% gel. Topical TMP-4 cream also seems to improve knee stiffness, stair climbing, and mobility similarly to diclofenac gel. However, patient impression of overall improvement was higher with diclofenac (110128). The validity of this study is limited by inadequate blinding.
• Schizophrenia. It is unclear if oral mangosteen is beneficial in schizophrenia. Details: A clinical study in adults with schizophrenia or schizoaffective disorder shows that taking mangosteen pericarp 1000 mg daily for 24 weeks does not improve total symptom severity when compared with placebo (106787). A secondary analysis of cognitive outcomes also did not demonstrate any differences (106790). More evidence is needed to rate mangosteen for these uses.

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EFFECTIVE

• Hypokalemia. Oral or intravenous potassium can treat and prevent hypokalemia. Details: Administering potassium orally or intravenously is effective for treating and preventing hypokalemia (15,107970). Oral potassium 20 mEq (780 mg of elemental potassium) is typically taken once daily to prevent hypokalemia (15,95010). Oral potassium 40-100 mEq (1560-3900 mg of elemental potassium) is typically taken in 2-5 divided doses daily to treat hypokalemia (95010). Doses should be limited to 40 mEq (1560 mg of elemental potassium), and the total dose should not exceed 200 mEq (7800 mg of elemental potassium) in 24 hours (95010). Potassium supplementation and route of administration should be individualized based on serum potassium level and patient status (15,107970).

LIKELY EFFECTIVE

• Hypertension. Oral potassium, via dietary intake or supplementation, reduces blood pressure. Details: Population research has found that higher dietary potassium consumption is associated with a lower risk of developing hypertension (1310,8817,69512). Additionally, most clinical research shows that potassium, taken orally as part of the diet or as a supplement, reduces systolic blood pressure by about 3-9.5 mmHg and diastolic blood pressure by about 2-6.4 mmHg in patients with or without hypertension (3385,92104,92106,95624,107974). In most of these studies, daily intake of potassium typically ranged from about 1500-7800 mg, with the most common intake being about 2340-2540 mg daily (92104,95624). However, some research shows that taking potassium does not lower systolic or diastolic blood pressure (69541,69550,107966). Differences in the patient populations, potassium intake, and salt intake could have contributed to the conflicting results. Potassium seems to be more effective for people with hypertension, low potassium levels, high daily sodium intake, and for Black adults (3384,3385,3386,92104,92106). Some research also shows that the greatest blood pressure-lowering effects of potassium occur at doses of about 3900-7800 mg daily (95624). A meta-analysis of clinical trials using a novel computational technique to assess both potassium intake and excretion suggests that the optimal blood pressure reduction occurs when taking about 1500 mg supplemental potassium daily or an overall intake of 4500-6500 mg potassium daily (105448). This analysis is limited by the heterogeneity and short duration of the included trials. There is also interest in utilizing low-sodium, high-potassium food substitutes to treat hypertension. Research shows that using salt substitutes containing 25% to 30% potassium chloride reduces systolic and diastolic blood pressure by 3-4.6 mmHg and 1 mmHg, respectively, when compared with regular table salt (107971,107976). In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) published guidelines recommending that patients with hypertension consume 3500-5000 mg of potassium daily (95680). This intake of potassium is expected to lower systolic blood pressure by about 4-5 mmHg in patients with hypertension and by about 2 mmHg in normotensive patients (3385). Although potassium supplements and dietary potassium both seem to be beneficial, the guidelines recommend getting potassium from dietary sources, since potassium-rich diets are usually heart-healthy (95680). Additionally, the US Food and Drug Administration (FDA) has determined that foods containing at least 350 mg potassium and that are low in sodium, saturated fat, and cholesterol can state that "diets containing foods that are good sources of potassium and low in sodium may reduce the risk of high blood pressure and stroke" (1310,8817).
• Kidney stones (nephrolithiasis). Oral prescription potassium citrate reduces the risk of kidney stone recurrence. It is unclear if non-prescription potassium citrate would be beneficial. Details: The American Urological Association (AUA) recommends potassium citrate therapy for patients with recurrent calcium stones and low urinary citrate, those with recurrent calcium or calcium oxalate stones without current metabolic abnormalities, and those with uric acid or cystine stones. The citrate component reduces urine calcium excretion and increases urine citrate and urine pH, which in turn alleviates crystal growth, formation, and aggregation. Sodium citrate may also be used to prevent stone recurrence; however, due to sodium's propensity to increase urine calcium excretion, potassium citrate remains the preferred salt formulation (107972). It is important to note that potassium citrate supplements are not equivalent to prescription potassium citrate products. Dose and duration of treatment is determined by a healthcare professional and individualized based on a patient's urinary citrate levels (107975,107989). Serum potassium levels should be monitored prior to starting potassium citrate, within 2 weeks of treatment initiation, and every 12 months (107975).

POSSIBLY EFFECTIVE

• Cardiovascular disease (CVD). Eating foods high in potassium and low in sodium might reduce the risk of cardiovascular disease. It is unclear if taking potassium supplements has the same benefit. Details: Large population studies in adults without prior CVD have found that higher dietary potassium intake is associated with a lower risk of cardiovascular events (109395,109399). One study found that daily potassium intake of about 3300 mg is associated with a 13% reduction in CVD risk when compared with intake of about 1920 mg (109399). The other study found that each additional 1000 mg of daily urinary potassium excretion, which is a marker of dietary intake, is associated with an 18% reduction in CVD risk (109395). Another observational study in over 15,000 adults with history of stroke or hypertension shows that replacing regular table salt with a substitute product containing 75% sodium chloride and 25% potassium chloride for an average of 5 years decreases the rate of stroke, major cardiovascular events, or death (107976). High quality clinical trials are needed to confirm this association. The US Food and Drug Administration (FDA) has determined that foods containing at least 350 mg potassium and that are low in sodium, saturated fat, and cholesterol can state that "diets containing foods that are good sources of potassium and low in sodium may reduce the risk of high blood pressure and stroke" (1310,8817).
• Stroke. Eating foods high in potassium and low in sodium might reduce the risk of stroke. It is unclear if taking potassium supplements has the same benefit. Details: Higher dietary intake of potassium seems to be associated with a lower risk of stroke. Population research has found that increasing dietary potassium intake by 1-1.5 grams daily is associated with up to a 20% reduced risk of stroke (92105,92107). Some population research has found that higher supplemental intake of potassium is associated with a 29% reduced risk of ischemic stroke. However, supplemental potassium intake is not found to be associated with a lower risk of hemorrhagic or total stroke (92107). An observational study in over 15,000 adults with history of stroke or hypertension shows that replacing regular table salt with a substitute product containing 75% sodium chloride and 25% potassium chloride for an average of 5 years decreases the rate of stroke, major cardiovascular events, or death (107976). High quality clinical trials are needed to confirm this association. The US Food and Drug Administration (FDA) has determined that foods containing at least 350 mg potassium and that are low in sodium, saturated fat, and cholesterol can state that "diets containing foods that are good sources of potassium and low in sodium may reduce the risk of high blood pressure and stroke" (1310,8817).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dental hypersensitivity. It is unclear if topical potassium improves dental hypersensitivity. Details: One meta-analysis of clinical research shows that using a dentifrice containing 5% potassium nitrite reduces dentin sensitivity when compared with a dentifrice that does not contain potassium nitrite (69549). Other clinical research published in a systematic review shows that potassium-containing toothpastes might reduce dentin sensitivity more than controls that do not contain potassium. However, these toothpastes might be less effective than other active toothpastes, such as those containing sodium monofluorophosphate, and the effect may result from a placebo effect, since the mechanism of action of potassium is unclear (69456).
• Diabetes. It is unclear if increasing dietary potassium reduces the risk of diabetes. Details: A meta-analysis of 7 large population studies has found that consuming dietary potassium 3300-3500 mg daily is associated with a 20% reduction in the risk of diabetes when compared with consumption below 1000 mg daily. Results were similar when studies that measured potassium intake with a dietary questionnaire were analyzed separately from those that measured intake based on urinary potassium excretion (110776). However, the validity of this finding is limited by the heterogeneity of the included studies. Furthermore, despite use of data from various databases, most studies included in the analysis were conducted by the same author.
• Impaired glucose tolerance (prediabetes). It is unclear if oral potassium improves glycemic control in prediabetes. Details: A small clinical study in Black patients with prediabetes shows that taking extended-release potassium (Klor-Con M10, Cardinal Health) 40 mEq daily as potassium chloride for 3 months does not improve glucose tolerance when compared with placebo. Although fasting glucose levels were slightly reduced in the potassium group when compared with placebo, both groups experienced a worsening of glucose intolerance, with no change in insulin levels or glycated hemoglobin (98533).
• Osteoporosis. Although there is interest in using oral potassium for osteoporosis, there is insufficient reliable information about the clinical effects of potassium for this condition.
• Physical performance. It is unclear if oral potassium improves physical performance in older adults. Details: Observational research in older adults has found that decreased dietary potassium intake and increased dietary sodium intake over 5 years is associated with worsened physical performance (105450).
• Systemic lupus erythematosus (SLE). It is unclear if oral potassium is beneficial in patients with SLE. Details: Observational research in patients with SLE has found that increased dietary potassium intake is not associated with improvements in disease activity scores or markers of cardiovascular disease, including lipid levels and blood pressure, when compared with low dietary potassium intake. However, higher potassium intake does seem to reduce the odds of having elevated levels of C-reactive protein, a marker of inflammation, in these patients (109397). More evidence is needed to rate potassium 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. Mangosteen has been used with apparent safety at a dose of up to 560 mg daily for 12 weeks (110127). It has also been used with apparent safety in combination with Sphaeranthus indicus (Meratrim, Laila Nutraceuticals) or Indian cassia (Cindura, Laila Nutraceuticals), for a total dose of 800 mg daily for up to 16 weeks (97876,97878,97879,101079). ...when used topically as a single dose. Mangosteen pericarp 4% gel has been applied once along the gum line with apparent safety (97875).

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

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LIKELY SAFE ...when used orally in doses up to 100 mEq total potassium daily, not to exceed 200 mEq in a 24-hour period (95010,107989). Oral potassium chloride and potassium citrate are FDA-approved prescription products (95010,107989). Larger doses increase the risk of hyperkalemia (15). ...when administered intravenously (IV) at appropriate infusion rates (95011). Parenteral potassium is an FDA-approved prescription product (15,95011). A tolerable upper intake level (UL) for potassium has not been established; however, potassium levels should be monitored in individuals at increased risk for hyperkalemia, such as those with kidney disease, heart failure, and adrenal insufficiency (100310,107966).

CHILDREN: LIKELY SAFE
when used orally and appropriately in dietary amounts. A tolerable upper intake level (UL) has not been established for healthy individuals (6243,100310).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in dietary amounts of 40-80 mEq daily (15). A tolerable upper intake level (UL) has not been established for healthy individuals (100310).

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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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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of mangosteen with anticoagulant or antiplatelet drugs may increase the risk of bleeding.  Details In vitro and animal research shows that gamma-mangostin, a constituent of mangosteen, is a potent and competitive antagonist of the serotonin 2A (5-HT2A) receptor. Antagonism of the 5-HT2A receptor is believed to reduce platelet aggregation (12017,61685,61686).

DONEPEZIL (Aricept) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of mangosteen with donepezil might increase the effects of donepezil.  Details Animal research shows that concomitant use of an aqueous extract of mangosteen pericarp with donepezil increases brain concentrations of donepezil at 4 hours by 64% without associated effects on systemic exposure (106791).

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ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = C Using ACEIs with high doses of potassium increases the risk of hyperkalemia.  Details ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = C Using ARBs with high doses of potassium increases the risk of hyperkalemia.  Details ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia (15,23207). However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628).

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = C Concomitant use increases the risk of hyperkalemia.  Details Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia (15).

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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 ...Orally, mangosteen is generally well tolerated. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Lactic acidosis.

Dermatologic ...Orally, mangosteen extract up to 560 mg daily has been reported to cause skin rash. It is not known if this side effect was related to mangosteen (97877).

Gastrointestinal ...Orally, mangosteen extract up to 560 mg daily has been reported to cause constipation, abnormal stool, abdominal discomfort, abdominal bloating, salivation, nausea and vomiting, and diarrhea. It is not known if these side effects were related to mangosteen (97877).

Neurologic/CNS ...Orally, mangosteen extract up to 560 mg daily has been reported to cause mild tiredness, headache, dizziness, and malaise. It is not known if these side effects were related to mangosteen (97877).

Pulmonary/Respiratory ...Orally, mangosteen extract up to 560 mg daily has been reported to cause dry throat, flu-like symptoms, cough, and nasal congestion. It is not known if these side effects were related to mangosteen (97877).

Renal ...Orally, mangosteen extract up to 560 mg daily has been reported to cause abnormal urination. It is not known if this side effect was related to mangosteen (97877). In one case report, a patient with chronic kidney disease and metabolic syndrome consumed mangosteen juice daily for 12 months and later presented with severe lactic acidosis. The juice was reported to contain 250 mg of mangosteen with 25 mg alpha-mangostin per ounce. Alpha-mangostin appears to inhibit mitochondrial function, disrupting the electron transport chain and adenosine triphosphate (ATP) production, causing accumulation of reactive oxygen species and inducing apoptosis. Researchers speculate that these effects might have led to lactic acidosis in this patient (16399).

Other ...Orally, mangosteen extract up to 560 mg daily has been reported to cause weight loss. It is not known if this side effect was related to mangosteen (97877).

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General ...Orally or intravenously, potassium is generally well-tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, belching, diarrhea, flatulence, nausea, and vomiting.
Serious Adverse Effects (Rare):
All ROAs: High potassium levels can cause arrhythmia, heart block, hypotension, and mental confusion.

Cardiovascular ...Orally or intravenously, high potassium levels can cause hypotension, cardiac arrhythmias, heart block, or cardiac arrest (15,16,3385,95011,95626,95630).

Gastrointestinal ...Orally or intravenously, high doses of potassium can cause, nausea, vomiting, abdominal pain, diarrhea, and flatulence (95010,95011). Bleeding duodenal ulcers have also been associated with ingestion of slow-release potassium tablets (69625,69672).

Neurologic/CNS ...Orally or intravenously, high potassium levels can cause paresthesia, generalized weakness, flaccid paralysis, listlessness, vertigo, or mental confusion (15,16,3385,95011).

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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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