Zeta Cleanse by Dr. Donsbach

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. Although there is interest in using oral or intravenous chelation therapy products for Alzheimer disease, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Angina. It is unclear if oral or intravenous chelation therapy products are beneficial for angina. Details: A small clinical trial (Program to Assess Alternative Treatment Strategies to Achieve Cardiac Health; PATCH) in patients with angina shows that 500-mL infusions of a multicomponent disodium ethylenediamine tetraacetic acid (EDTA) chelation solution (Endrate) does not improve exercise capacity or time to ischemia when compared with a placebo containing all components other than EDTA. The dose of EDTA was 40 mg/kg (maximum 3 grams per dose) and was provided over a period of 3 hours. Infusions took place twice weekly for 15 weeks and then monthly for 3 months. Each infusion also provided magnesium sulfate 750 mg, ascorbic acid 5 grams, and sodium bicarbonate 5 grams. All patients also took an oral multivitamin/multimineral product (108104). This study may have been underpowered to detect differences between groups. There is currently no information suggesting that the oral use of chelation therapy products is beneficial.
• Arsenic poisoning. Although there is interest in using topical chelation therapy products for arsenic poisoning, there is insufficient reliable information about the clinical effects of topical chelation therapy products for this condition.
• Atherosclerosis. Although there is interest in using oral chelation therapy products for atherosclerosis, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral chelation therapy products for ADHD, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose.
• Atopic disease. Although there is interest in using oral chelation therapy products for atopic disease, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose.
• Autism spectrum disorder. It is unclear if oral or topical chelation therapy products are beneficial for autism spectrum disorder. Details: Various chelation therapy products have been investigated in clinical research. One preliminary clinical trial in children aged 3-8 years with autism spectrum disorder shows that taking dimercaptosuccinic acid (DMSA) 10 mg/kg three times daily as chelation therapy does not improve sociability, communication with speech or language, or general stereotypical behaviors when compared with placebo. The DMSA was taken for 3 days and then repeated up to 6 times, with 11 days off between treatment periods. Prior to the initiation of this phase of the study, all children received at least one 3-day round of chelation therapy to ensure the excretion of high amounts of heavy metals; however, heavy metal excretion was not compared between groups . Also, half of the children received topical glutathione for 7 days (21057,108099,108109). Other preliminary clinical research in children aged 3-9 years with autism spectrum disorder shows that taking a single dose of DMSA 10 mg/kg increases urinary excretion of cadmium, mercury, and lead. Taking DMSA monthly for 6 months improves overall behavior when compared with baseline. However, only specific behaviors, such as relating to people, imitation, and communication, were improved; other behaviors, including emotional, visual, auditory, or intellectual responses, were not improved (108110). The validity of these findings is limited by the lack of a comparator group. Small clinical studies have also evaluated other chelation therapy products in children with autism spectrum disorder. These include rectal thiamine tetrahydrofurfuryl disulfide (108111) and oral, intravenous, rectal, or topical 2,3-dimercaptopropane-1-sulfonate (DMPS) (108098). However, there is insufficient reliable information available regarding their effects.
• Cancer. Although there is interest in using oral chelation therapy products for cancer, there is insufficient reliable information about the clinical effects of chelation therapy products for this use.
• Cardiovascular disease (CVD). It is unclear if oral or intravenous chelation therapy products are beneficial for CVD. Details: One large clinical study (the Trial to Assess Chelation Therapy; TACT) in adults with stable coronary disease following a recent myocardial infarction (MI) shows that receiving 500-mL infusions of a multicomponent disodium ethylenediamine tetraacetic acid (EDTA) chelation solution, with or without oral high-dose vitamins, reduces the composite risk of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization by about 18% over 5 years. However, there was no effect of EDTA on the risk of these individual endpoints. A sub-group analysis shows that the risk of this composite outcome is reduced by up to 41% in patients who also have diabetes, with no reduction in patients without diabetes (94983,94985). Also, receiving just the multicomponent disodium EDTA chelation solution without oral high-dose vitamins does not reduce the risk of this composite outcome when compared with placebo, even in the subgroup of patients with diabetes (94986). Each infusion provided EDTA 3 grams over a period of at least 3 hours in combination with ascorbic acid 7 grams, magnesium chloride 2 grams, potassium chloride 2 mEq, sodium bicarbonate 840 mg, pantothenic acid 250 mg, thiamine 100 mg, pyridoxine 100 mg, procaine hydrochloride 100 mg, and heparin 2500 units (94983,94985,94986). Significant limitations of the trial, including missing data and possible unblinding, limit the reliability of these findings (95697).
• Hypertension. Although there is interest in using oral chelation therapy products for hypertension, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Influenza. Although there is interest in using oral chelation therapy products for influenza, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose.
• Lead toxicity. Although there is interest in using topical chelation therapy products for lead toxicity, there is insufficient reliable information about the clinical effects of topical chelation therapy products for this condition.
• Mercury toxicity. Although there is interest in topical chelation therapy products for mercury toxicity, there is insufficient reliable information about the clinical effects of topical chelation therapy products for this condition.
• Osteoporosis. Although there is interest in using oral chelation therapy products for osteoporosis, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Parkinson disease. Although there is interest in using oral chelation therapy products for Parkinson disease, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Peripheral arterial disease (PAD). It is unclear if oral or intravenous chelation therapy products are beneficial for PAD. Details: Individual preliminary clinical trials included in a systematic review have shown that intravenous disodium ethylenediamine tetraacetic acid (EDTA) has no beneficial effect on blood flow, walking distance, pain-free walking distance, blood lipid levels, or well-being in patients with PAD (5752,5753,5754,108103). Most studies have used EDTA 3 grams twice weekly, usually in combination with vitamins and minerals, over a period of up to 10 weeks (5753,108103). In addition, there is no information suggesting that the oral use of EDTA is beneficial.
• Uterine fibroids. Although there is interest in using oral chelation therapy products for uterine fibroids, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose. More evidence is needed to rate chelation therapy products 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 UNSAFE ...when unregulated chelation therapy products are used orally or parentally or when prescription chelation therapy products are used for unproven indications and/or in unapproved doses or routes of administration. The American College of Medical Toxicology and The American Academy of Clinical Toxicology recommend against the unapproved use of chelation therapy products (108106). Chelation therapy products can result in severe side effects including dehydration, hypocalcemia, kidney failure, neurodevelopmental toxicity, and death (107700,108095,108096,108105,108106,108107). Also, infusion of the disodium form of EDTA over less than 3 hours can cause severe, life-threatening adverse effects including hypocalcemia and death (5737).

CHILDREN: POSSIBLY UNSAFE
when unregulated chelation therapy products are used orally or parentally or when prescription chelation therapy products are used for unproven indications and/or in unapproved doses or routes of administration. The American College of Medical Toxicology and The American Academy of Clinical Toxicology recommend against the unapproved use of chelation therapy products (108106). Chelation therapy products can result in severe side effects including dehydration, hypocalcemia, kidney failure, neurodevelopmental toxicity, and death (107700,108095,108096,108105,108106,108107).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when unregulated chelation therapy products are used orally or parentally or when prescription chelation therapy products are used for unproven indications and/or in unapproved doses or routes of administration. The American College of Medical Toxicology and The American Academy of Clinical Toxicology recommend against the unapproved use of chelation therapy products (108106). Chelation therapy products can have teratogenic effects and result in severe side effects including dehydration, hypocalcemia, kidney failure, neurodevelopmental toxicity, and death (107700,108095,108096,108105,108106,108107).

(Read more about CHELATION THERAPY PRODUCTS)

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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DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Concomitant use of ethylenediamine tetraacetic acid (EDTA) and potassium-depleting diuretics might increase the risk for hypokalemia.  Details EDTA can decrease serum potassium levels and increase excretion of potassium (15).

INSULIN Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Ethylenediamine tetraacetic acid (EDTA) can decrease the activity of insulin and increase the risk for hypoglycemia.  Details Concomitant use of disodium EDTA with insulin can cause severe decreases in blood glucose concentrations (5737,5771). Additionally, EDTA chelates zinc in insulin products (15) and might interfere with the onset and duration of activity of various insulin preparations.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, disodium ethylenediamine tetraacetic acid (EDTA) can decrease the anticoagulant effects of warfarin.  Details Disodium EDTA has been reported to decrease international normalized ratio (INR) in a patient taking warfarin (4611).

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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 ...The use of chelation therapy products for unproven indications, or in unapproved doses or routes of administration, is generally considered to be unsafe.
Most Common Adverse Effects:
Orally: Gastrointestinal upset, nausea.
Intravenous: Abdominal cramps, anorexia, burning and pain at infusion site, diarrhea, headache, nausea, vomiting.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, Stevens-Johnson syndrome.
Intravenous: Allergic reactions, arrhythmias, convulsions, death, heart failure, hypercalcemia, hypocalcemia, insulin shock, kidney failure, paresthesia, respiratory arrest, tetany, thrombophlebitis.

Cardiovascular ...Intravenously, chelation therapy products such as 2,3-dimercaptopropane-1-sulfonate (DMPS) or ethylenediamene tetraacetic acid (EDTA) have been associated with hypotension and irregular heartbeat (5737,5771,5772,108105,108106). Intravenously, EDTA can also cause thrombophlebitis (108099,108103). Disodium EDTA, when given as a rapid infusion or highly concentrated solution, can cause hypocalcemia, severe cardiac arrhythmias, respiratory arrest, and death (15,108102).
There are at least three case reports of intravenous chelation therapy-related hypocalcemia resulting in cardiac arrest. Two cases involved the use of disodium EDTA in children and one involved the unapproved use of an unknown type of EDTA over a 10- to 15-minute infusion in an adult (107700,108095,108096,108097,108105). At least in part because of these cases, disodium EDTA is no longer FDA-approved (108105). In a large clinical trial in patients with a previous myocardial infarction, the rate of hypocalcemia was 6.2% in patients given disodium EDTA, compared with 3.5% of those given placebo; however, disodium EDTA did not increase the risk of heart failure or death (94985).

Dermatologic ...There is a case report of Stevens-Johnson syndrome after two weeks of oral 2,3-dimercaptopropane-1-sulfonate (DMPS) chelation therapy in a child with chronic mercury exposure. Symptoms included a widespread eruption of red, itchy macules which gradually improved after discontinuation of DMPS therapy (108112). Rash has also been reported in patients given intravenous DMPS or oral dimercaptosuccinic acid (DMSA) (108099).
Intravenously, ethylenediamene tetraacetic acid (EDTA) can commonly cause exfoliative dermatitis (15,108103) and a burning sensation and pain at the site of infusion (5744,108103).

Endocrine ...Intravenously, calcium disodium ethylenediamene tetraacetic acid (EDTA) can cause zinc deficiency (5771,5772) and hypercalcemia (5771,5772). Disodium EDTA can occasionally reduce magnesium and potassium serum concentrations (5771,5772), and rarely cause insulin shock (5737).
Disodium EDTA, when given as a rapid infusion or highly concentrated solution, can cause hypocalcemia, leading to tetany, convulsions, cardiac arrhythmias, cardiac failure, respiratory arrest, and death. This has occasionally occurred when the disodium form of EDTA was used in error, instead of the calcium disodium form (15,94984,94985,107700,108095,108096,108097,108099,108105).

Gastrointestinal ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can commonly cause abdominal cramps, anorexia, nausea, vomiting, and diarrhea (15). EDTA can also sometimes cause thirst (15).
When given orally or intravenously, 2,3-dimercaptopropane-1-sulfonate (DMPS) has caused nausea and dysgeusia.
Orally, dimercaptosuccinic acid (DMSA) has caused gastrointestinal upset and diminished appetite (108099).

Hematologic ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can sometimes cause anemia (15), prolonged prothrombin time (5737) and transient bone marrow suppression (5737,5772).

Hepatic ...Intravenously, the calcium disodium form of ethylenediamene tetraacetic acid (EDTA) can cause mild elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and decreased alkaline phosphatase (ALP) levels (15,108102).
Orally, dimercaptosuccinic acid (DMSA) has been associated with mild elevations in liver transaminase levels (108105).

Immunologic ...Intravenously, disodium ethylenediamene tetraacetic acid (EDTA) can rarely cause histamine-like reactions (5737). There are rare reports of allergic reactions to EDTA given as a nasal provocation, topically, intradermally, and subcutaneously (94992). In one case report, a 57-year-old male presented with pruritus on the hands and feet, as well as urticaria and swelling of the face, following subcutaneous injection with a local anesthetic containing EDTA. Allergy to other ingredients in the anesthetic was ruled out, and intradermal and subcutaneous testing with calcium disodium EDTA confirmed the allergic response. The patient also reacted to radio-contrast medium containing EDTA (94992).
Topically, application of EDTA in cosmetics, shampoos, and other products has rarely been reported to cause contact dermatitis (94992).
Orally, dimercaptosuccinic acid (DMSA) has been associated with allergic reactions (108105).

Musculoskeletal ...Intravenously, disodium ethylenediamene tetraacetic acid (EDTA) can occasionally cause muscle cramps, back pains, muscle weakness, and myalgias (15). In a large clinical trial in patients with a previous myocardial infarction, the rate of hypocalcemia was 6.2% in patients given disodium EDTA, compared with 3.5% of those given placebo; however, only one patient had associated muscle cramping leading to a hospital visit (94985).

Neurologic/CNS ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can commonly cause headache and faintness (15,108103). EDTA can also sometimes cause fever, chills, fatigue, and malaise (15,108099). Disodium EDTA can occasionally cause tremors, tingling, and paresthesias (15).
Orally, dimercaptosuccinic acid (DMSA) was associated with lethargy in one child in a clinical trial. Other possible adverse effects associated with DMSA included sleep problems (108099).

Pulmonary/Respiratory ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can sometimes increase sneezing and nasal congestion (15). Inhalation of disodium EDTA contained in nebulizer solutions has been reported to cause dose-related bronchoconstriction (5765).

Renal ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can sometimes cause urinary urgency and frequency (5772). However, the most serious adverse effect of EDTA is kidney toxicity (5772,108095,108099,108102) for doses greater than 3 grams daily (15). In a clinical trial in patients with angina, intravenous disodium EDTA has resulted in an elevation of serum creatinine (108104). EDTA can cause nocturia, hyperuricemia, polyuria, dysuria, oliguria, proteinuria, glycosuria, hematuria. and distal tubule and glomeruli changes (15). EDTA can also cause acute renal tubular necrosis, renal insufficiency, and renal failure (5772).

(Read more about CHELATION THERAPY PRODUCTS)

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).

(Read more about POTASSIUM)

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).

(Read more about SODIUM)