Cordygen VO2 Ultra by Millennium Sport Technologies

POSSIBLY INEFFECTIVE

• Athletic performance. Taking cordyceps orally does not seem to improve athletic performance in adults. Details: One small clinical study in endurance-trained cyclists shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) 3.15 grams daily for 5 weeks does not improve endurance time trials or aerobic capacity when compared with placebo (12095). Another small study in healthy elderly adults shows that taking the same cordyceps preparation (CordyMax Cs-4) 3 grams daily for 12 weeks does not improve exercise performance when compared with placebo (46120). Research also shows that taking combination products containing cordyceps and other ingredients does not improve athletic performance when compared with control. These products have combined cordyceps (CordyMax Cs-4) 1000 mg with rhodiola 300 mg (46091) or cordyceps (CordyMax Cs-4) 2000 mg with roseroot 600 mg (Optygen, First Endurance) (15573); liquid and powdered cordyceps formulations with reishi mushroom, shiitake mushroom, bamboo, and honey (Fohow oral liquid and Fohow lingzhi capsules, FOHOW Technology Investment Group Co. Ltd.) (98686); and cordyceps (form unknown) 1.2 grams with a 930 mg mixture of extracts of ashwagandha root, green tea leaf, rhodiola root, and astragalus root (Shroom Tech Sport, Onnit Labs) (105079).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Arrhythmia. Although there is interest in using oral cordyceps for arrhythmia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Asthma. Oral cordyceps has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with asthma shows that a 619 mg capsule containing equal weights of the dried aqueous extracts of cordyceps, astragalus, skullcap, Radix stemonae, and Bulbus fritillariae daily for 6 months does not reduce the need for medication or improve symptoms when compared with placebo (32935).
• Chronic kidney disease (CKD). Small clinical studies suggest that oral cordyceps may modestly improve biomarkers in some patients with CKD. Details: A meta-analysis of clinical research in patients in China with CKD shows that taking cordyceps 0.6-2 grams orally three times daily, along with standard treatment, seems to decrease serum creatinine levels by 0.6 mg/dL and increase creatinine clearance by 9.2 mL/min when compared with standard treatment alone (92829). Another meta-analysis of clinical studies in patients in China with diabetic kidney disease shows that taking cordyceps 0.5-2 grams orally three times daily along with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) decreases blood urea nitrogen by 2 mg/dL and decreases serum creatinine levels by 0.1 mg/dL when compared with ACEI/ARB treatment alone (92830). Most individual studies in these analyses used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (92829,92830). Both of these analyses are limited by the low methodological quality and short duration (usually 1-6 months) of most of the included studies.
• Chronic obstructive pulmonary disease (COPD). Preliminary clinical studies suggest that oral cordyceps may modestly improve symptoms of COPD. Details: A meta-analysis of preliminary clinical research in patients with moderate or severe COPD shows that taking cordyceps alone or as part of a formulation containing other products for up to 12 months improves lung function and reduces the incidence of an acute exacerbation by a small amount. Also, the distance walked in 6 minutes is increased by about 45 meters, which was considered clinically meaningful. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products, in combination with conventional treatments with conventional treatments alone (109705). This analysis is limited by the low methodological quality of the included studies.
• Contrast induced nephropathy. Small clinical studies suggest that oral cordyceps may modestly reduce contrast induced nephropathy. Details: A preliminary clinical study in patients with diabetic nephropathy shows that taking a specific cordyceps mycelial product (Corbrin; CS-C-Q80) 2-3 grams orally three times daily for 3 days before and after angiography reduces the risk of contrast induced nephropathy by about 48% to 66% when compared to standard treatment (92827). However, other preliminary clinical research in patients with stable angina pectoris shows that taking the same cordyceps product 3 grams orally three times daily for 3 days before and after angioplasty does not decrease the prevalence of contrast induced nephropathy when compared to standard therapy (92826). Reasons for these discrepancies are not clear but may relate to the small size and heterogenous populations in these studies.
• Diabetic nephropathy. Early research suggests that oral cordyceps may modestly improve kidney function in patients with diabetic kidney disease. Details: A meta-analysis of low to moderate quality clinical research in patients with diabetic kidney disease shows that taking cordyceps as adjunctive therapy to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for 2-24 weeks modestly improves kidney function when compared to these medications alone. Kidney function was based on markers such as blood creatinine and urea nitrogen, as well as urinary albumin and total protein. There were also modest improvements in systolic and diastolic blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol. There was no effect on glycemic indices. The effect of cordyceps on disease progression or cardiovascular events is unclear (111903).
• Cough. Although there is interest in using oral cordyceps for cough, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Fatigue. Although there is interest in using oral cordyceps for fatigue, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Hepatitis B. Although there is interest in using oral cordyceps for hepatitis B, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Hypercholesterolemia. Although there is interest in using oral cordyceps for hypercholesterolemia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Kidney failure. Small clinical studies suggest that oral cordyceps may improve inflammatory markers in patients on hemodialysis. Details: A meta-analysis of small clinical trials in patients in China on hemodialysis suggests that adding cordyceps to standard treatment does not seem to improve serum creatinine levels but may improve certain markers of inflammation, such as C-reactive protein, when compared with placebo. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (105076).
• Kidney transplant. Small clinical studies suggest that oral cordyceps is no better than standard treatment in patients with kidney transplant. Details: A meta-analysis of 4 heterogeneous clinical trials evaluating patients in China immediately post-kidney transplant or patients with complications post-kidney transplant suggests that adding cordyceps to standard therapy with cyclosporine and steroids is no better than adding azathioprine 50-150 mg for improving overall survival or graft survival or reducing rejection risk. However, there was a non-significant trend to reduced risk of graft rejection in the cordyceps group (95905). A higher quality systematic review, which determined the available studies were too heterogeneous to pool together in a meta-analysis, suggests that adding cordyceps 3-6 grams to standard therapy daily is no better than azathioprine or cyclosporine for improving organ rejection, kidney function, or survival in patients after kidney transplant (92828). All individual studies in these analyses used Bailing (Cs-C-Q80) fermented cordyceps mycelial product (95905,92828).
• Sexual dysfunction. It is unclear if oral cordyceps is beneficial in patients with sexual dysfunction. Details: Preliminary clinical research shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) approximately 3 grams daily for 40 days can improve symptoms of hyposexuality in 66% of patients, compared with 32% of patients taking natural cordyceps and 24% of patients taking placebo (46145).
• Tinnitus. Although there is interest in using oral cordyceps for tinnitus, there is insufficient reliable information about the clinical effects of cordyceps for this condition. More evidence is needed to rate cordyceps for these uses.

(Read more about CORDYCEPS)

POSSIBLY EFFECTIVE

• Diabetes. Oral jiaogulan extract powder may improve glycemic control in patients newly diagnosed with type 2 diabetes when used alone or with diabetes medications. Details: A meta-analysis of two small clinical trials in adults with newly diagnosed type 2 diabetes shows that taking jiaogulan whole plant extract powder, 1.5 grams dissolved in 60 mL of room temperature water, twice daily before meals for 8-12 weeks reduces glycated hemoglobin by 1%, fasting blood glucose by 29 mg/dL, and post-prandial blood glucose by 80 mg/dL when compared with green tea (111503). In one of the trials, both the jiaogulan and the placebo groups were also started on a sulfonylurea 4 weeks prior to the study and remained on it throughout the trial (95519). In the other trial no participants were taking diabetes medications (95520). Additionally, a very small cross-over trial that was not included in the aforementioned meta-analysis shows this same jiaogulan protocol reduces fasting blood glucose and improves insulin sensitivity at 4 weeks when compared with green tea in adults newly diagnosed with type 2 diabetes (94054). The washout period was 2 weeks, and switching to placebo reversed the improvements in glycemic control. All three clinical trials above were conducted in Vietnam by the same research group with the same jiaogulan extract product and protocol (94054,95519,95520). The validity of these findings may be limited by the use of a potentially non-inert green tea placebo, as green tea itself has been studied for its effects on preventing and treating diabetes.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral jiaogulan for aging, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
• Athletic performance. Although there has been interest in using oral jiaogulan for athletic performance, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
• Cancer. Although there has been interest in using oral jiaogulan for preventing or treating cancer, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
• Cardiovascular disease (CVD). Although there has been interest in using oral jiaogulan for CVD, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
• Hypercholesterolemia. Small clinical studies suggest that oral jiaogulan extract may lower cholesterol levels in patients with hypercholesterolemia. Details: Two small clinical studies in patients with hypercholesterolemia show that taking jiaogulan extract can decrease total cholesterol and increase the high-density lipoprotein (HDL)/total cholesterol ratio (7069,7070). The dose of jiaogulan extract used in one study was 10 mg three times daily (7069).
• Hypertension. Although there has been interest in using oral jiaogulan for hypertension, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
• Memory. Although there has been interest in using oral jiaogulan for memory, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral jiaogulan extract is beneficial in patients with NAFLD. Details: One small clinical study in patients with NAFLD shows that taking jiaogulan extract three times daily for 4 months in conjunction with controlled dieting does not improve markers of liver function, body mass index, cholesterol levels, kidney function, or glucose levels when compared with placebo (57056).
• Obesity. Small clinical studies suggest that oral jiaogulan extract may slightly reduce body weight in patients who are overweight or obese. Details: Two small clinical studies in adult patients who are overweight or obese show that taking jiaogulan extract 225 mg twice daily for 12-16 weeks reduces body weight by 1.3 kg and body mass index (BMI) by around 0.4 kg/m2 when compared with placebo (94058,106651).
• Respiratory tract infections. Although there has been interest in using oral jiaogulan for various respiratory tract infections, including bronchitis, rhinosinusitis, and the common cold, there is insufficient reliable information about the clinical effects of jiaogulan for these conditions.
• Stress. It is unclear if oral jiaogulan extract is beneficial in patients with chronic stress. Details: One small clinical study in healthy adults with self-perceived chronic stress and anxiety at baseline, but without a confirmed diagnosis of anxiety, depression, or other mental health disorders, shows that taking jiaogulan extract 200 mg twice daily for 8 weeks while being exposed to repetitive stressful tasks decreases anxiety scores by almost 17% when compared with placebo. While no subjective assessments of stress were included, salivary cortisol levels and other stress markers did not improve with jiaogulan when compared with placebo (100961). More evidence is needed to rate jiaogulan for these uses.

(Read more about JIAOGULAN)

EFFECTIVE

• Bowel preparation. Oral sodium phosphate is effective for cleansing the colon in preparation for colonoscopy; however, it is unclear whether sodium phosphate is as effective as polyethylene glycol (PEG) solution. Some products are approved by the US Food and Drug Administration (FDA) for this use. However, due to the potential for kidney damage, sodium phosphate is not recommended as first-line therapy. Details: Sodium phosphate tablets (OsmoPrep, Salix Pharmaceuticals; Visicol, Salix Pharmaceuticals) are FDA-approved for cleansing the colon in preparation for colonoscopy. Clinical research shows that using the OsmoPrep formulation can achieve an "excellent" or "good" response rate, which is defined as having 90% of the mucosa visible with only some or little suctioning needed, in 94% to 97% of patients (88133). Similarly, using the specific product Visicol has been shown to achieve an excellent or good response rate in 82% to 86% of patients (94674). Non-FDA-approved sodium phosphate products have also been investigated. One such product (Fleet Phospho-soda, C. B. Fleet Co.) has been shown to achieve adequate bowel cleansing in 23% to 89% of patients (93846,94673). Another sodium phosphate tablet preparation (Clicolon tablets, Korea Pharma Co.) has been shown to achieve adequate bowel cleansing in 63% to 93% of patients (93848,93850,93853). Excellent or good bowel cleansing was found in 98.6% of patients using a 32-tablet regimen of other sodium phosphate tablets (Quiklean, Universal Integrated Corporation) (107008). Reasons for the differences in the percentage of patients who achieve adequate bowel cleansing with the same sodium phosphate product may relate to the method used to analyze bowel cleansing, differences in diet followed during bowel cleansing, and demographic factors (93846,93848,93850,93853). Various preparations (OsmoPrep, Salix Pharmaceuticals; Visicol, Salix Pharmaceuticals; Clicolon tablets, Korea Pharma Co.; Quiklean, Universal Integrated Corporation) have been used which contain 1.102 grams of sodium phosphate monobasic monohydrate and 0.398 grams of sodium phosphate dibasic anhydrous. These products have been taken as 3-4 tablets with 8 ounces of water every 15 minutes for a total of 20 tablets the evening before colonoscopy, and 3-4 tablets with 8 ounces of water every 15 minutes for a total of 12-20 tablets the morning of a colonoscopy (88133,93848,93850,94674,107008). Also, sodium phosphate solution (Fleet Phospho-soda, C. B. Fleet Co.) containing sodium hydrogen phosphate 24.4 grams and disodium phosphate dodecahydrate 10.8 grams has also been used the morning and evening before the procedure (93846). Numerous publications have compared the bowel cleansing activity of sodium phosphate with PEG solution. When given as a split-overnight dosage, sodium phosphate is about as effective as PEG solutions in achieving adequate bowel cleansing. However, when day-before dosage is used, PEG is more effective for bowel cleansing than sodium phosphate (93861,93862,107008). Sodium phosphate and PEG may have different effectiveness depending on the colonic site assessed. When only trials assessing descending colon cleansing are considered, sodium phosphate is found to work similarly to PEG solutions. When only studies assessing ascending colon cleansing are considered, PEG is more effective for bowel cleansing than sodium phosphate (93861). Also, a large clinical trial in outpatients scheduled for non-sedated colonoscopy shows that receiving PEG resulted in an easier insertion and a less painful colonoscopy when compared with receiving sodium phosphate (104473). However, in patients with chronic constipation, sodium phosphate seems to be preferable. A meta-analysis of three small clinical studies in adults with chronic constipation shows that using sodium phosphate has an 87% greater chance of a successful bowel preparation when compared with using PEG (104472). Sodium phosphate is not recommended as first-line therapy for bowel preparation prior to colonoscopy due to the potential for kidney damage (93863,94672). In fact, one sodium phosphate preparation (Fleet Phospho-soda, C. B. Fleet Co.) that was previously approved as an over-the-counter supplement for bowel preparation in the US was withdrawn from the market for this indication in December 2008 due to concerns for phosphate-induced kidney disease (94672). Of the sodium phosphate products that are still approved by the FDA, current guidelines recommend that these products not be used for bowel cleansing in patients with kidney disease, pre-existing electrolyte disturbances, congestive heart failure, cirrhosis, ascites, or inflammatory bowel disease. Guidelines also recommend that caution should be used if these products are prescribed for patients who are elderly, hypertensive, or taking certain classes of drugs (94672). For small bowel preparation for endoscopy, a meta-analysis suggests that sodium phosphate is no more effective than fasting alone (93860).
• Hypophosphatemia. Oral or intravenous phosphate salts are effective for the prevention or treatment of hypophosphatemia. Some products are approved by the US Food and Drug Administration (FDA) for this use. Details: Taking sodium or potassium phosphate orally is effective for preventing and treating hypophosphatemia (15). Treating hypophosphatemia with oral phosphates requires monitoring of serum electrolyte levels to determine appropriate dosing (15). The FDA-approved intravenous (IV) product is also used for the correction of hypophosphatemia (8302,8303,88135). FDA-approved intravenous (IV) sodium phosphate or potassium phosphate 15-30 mmol is typically given over 2-12 hours. Higher doses have been used if needed to increase efficacy (8302,8303,88135).

LIKELY EFFECTIVE

• Constipation. Oral or rectal sodium phosphate is approved by the US Food and Drug Administration (FDA) as an ingredient in over-the-counter (OTC) products to treat constipation. Details: Sodium phosphate is an FDA-permitted ingredient of oral and rectal OTC products intended for the treatment of constipation (88107).
• Dyspepsia. Oral aluminum phosphate and calcium phosphate are approved by the US Food and Drug Administration (FDA) as ingredients in over-the-counter (OTC) antacids. Details: Aluminum phosphate and calcium phosphate are FDA-permitted ingredients of oral OTC products intended for use as antacids (88107).
• Hypercalcemia. Although other treatments are preferred, oral non-calcium phosphate salts are beneficial for treatment of mild to moderate hypercalcemia. Details: Taking phosphate salts (except calcium phosphate) orally is effective for treating mild to moderate hypercalcemia (88144,88145). Treating hypercalcemia with oral phosphates requires monitoring of serum electrolyte levels to determine appropriate dosing (15); other agents are now preferred (6479). Intravenous phosphates should be avoided due to the risk of calcium precipitation in vital organs (metastatic calcification) (15,88144,88145).

POSSIBLY EFFECTIVE

• Kidney stones (nephrolithiasis). Oral potassium phosphate seems to be beneficial for prevention of kidney stones in individuals with hypercalciuria. Details: Taking potassium phosphate orally may help prevent calcium oxalate kidney stones in patients with hypercalciuria (6470). Clinical research in adults with absorptive hypercalciuria and at high risk for stone formation shows that taking a specific slow-release potassium phosphate product (Uro-Phos-K, Mission Pharmacal), providing phosphate 620 mg orally twice daily for 4 days, reduces urinary calcium excretion by 35% to 40% (2208,2209). Potassium and sodium phosphate salts providing 1200-1500 mg of elemental phosphate daily have been used (2209,6470).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. The evidence is mixed as to whether oral sodium phosphate improves cycling or running performance. Most research suggests that oral calcium phosphate and potassium phosphate are not beneficial. Details: Clinical research shows that taking calcium phosphate or potassium phosphate orally does not improve running or cycling performance (2499,9300,8301). Evidence for the use of sodium phosphate to improve cycling performance is mixed. One very small clinical study shows that taking sodium phosphate as tribasic sodium phosphate dodecahydrate for 6 days before a 10-mile cycling trial increases mean power output by about 10% and decreases the time needed to complete the trial by 3% in trained male cyclists (88150). Other small clinical trials in trained cyclists show that taking the same form of sodium phosphate as 50 mg/kg of fat-free mass in four divided doses daily for 6 days modestly improves work, power output, and peak oxygen uptake and reduces heart rate during high-intensity cycling exercise when compared to baseline (93857,93858,93859,107007). However, conflicting research shows that taking a similar dosage of this form of sodium phosphate does not improve time trial performance, work accomplished relative to energy expenditure, power output, or oxygen uptake in trained cyclists (93855,93856,107007). Sodium phosphate has also been evaluated for improving running performance, with mixed findings. Two small clinical trials in female athletes show that tribasic sodium phosphate dodecahydrate 50 mg/kg of fat-free mass taken in four divided doses daily for 6 days moderately improves repeated sprint times when compared with placebo (93843,93844). However, taking the same dosage does not significantly improve sprint times in male athletes (93849). Also, sodium phosphate does not seem to improve endurance or aerobic capacity in treadmill tests (8301,93854). Reasons for the discrepancies regarding the effects of sodium phosphate on athletic performance are not entirely clear, but likely relate to the very small number of participants in the included trials.
• Diabetic ketoacidosis. Potassium phosphate infusion is not recommended as first-line therapy for adults with diabetic ketoacidosis. Details: Clinical research shows that intravenous infusion of potassium phosphate 8.5 mmol/hour (approximately 6 grams of phosphate over 24 hours) along with potassium chloride 12.5 mEq/hour provides no benefit over potassium chloride alone in adults with diabetic ketoacidosis (88149). Guidelines for the treatment of diabetic ketoacidosis in the both the US and UK do not recommend phosphate replacement for most patients. However, it may be considered in specific cases, such as cardiac dysfunction, anemia, respiratory depression, and serum phosphate concentrations below 1 mg/dL (107349,107350A).
• Osteoporosis. Calcium phosphate seems to be beneficial for bone density improvement; however, it does not seem to be more beneficial than calcium carbonate. Details: In postmenopausal adults with osteoporosis and low phosphate intakes, taking calcium 1800 mg daily as tricalcium phosphate for 12 months improves lumbar spine and hip densities. However, it is no more effective than taking the same amount of calcium as calcium carbonate (93847). The calcium products were used in combination subcutaneous teriparatide and oral vitamin D (cholecalciferol) 1000 IU daily.
• Refeeding syndrome. It is unclear if intravenous potassium phosphate or sodium phosphate is beneficial for prevention of refeeding syndrome. Details: Preliminary clinical research shows that giving intravenous sodium and potassium phosphates, 50 mmol (1.56 grams) phosphate over 24 hours, prevents the refeeding syndrome seen when restarting adequate nutrition after severe malnutrition or starvation when compared with historical controls (88148). More evidence is needed to rate phosphate salts for these uses.

(Read more about PHOSPHATE SALTS)

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.

(Read more about POTASSIUM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Altitude sickness. It is unclear if oral rhodiola is beneficial for altitude sickness. Details: Preliminary clinical research shows that taking rhodiola 447 mg four times daily for 7 days does not improve blood oxygenation or markers of oxidative stress when compared with placebo in subjects exposed to simulated high-altitude conditions (25402).
• Anthracycline cardiotoxicity. It is unclear if oral rhodiola is beneficial for epirubicin-induced cardiotoxicity. Details: Preliminary clinical research in breast cancer patients shows that taking salidroside, a constituent of rhodiola, 600 mg daily, beginning one week prior to chemotherapy and continuing throughout chemotherapy administration, reduces epirubicin-induced early left ventricular regional systolic dysfunction when compared with placebo (90434).
• Anxiety. It is unclear if oral rhodiola is beneficial for anxiety. Details: Preliminary clinical research in college students with anxiety shows that taking a specific dried rhodiola extract (Vitango, Schwabe Pharma) 200 mg twice daily for 14 days modestly reduces reported levels of anxiety, anger, confusion, negative mood, and stress when compared with a control group. However, rhodiola extract does not seem to improve cognition (96462).
• Arrhythmia. Although there has been interest in using oral rhodiola for arrhythmia, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Athletic performance. The evidence related to the use of rhodiola for athletic performance is mixed, although specific standardized extracts might be beneficial for certain performance endpoints. Details: The available evidence for rhodiola in athletic performance includes small clinical trials in recreationally active or trained athletes. Trials using rhodiola extracts standardized to 3% rosavins and 1% salidroside (eg. Finzelberg, GmbH) show that taking 3 mg/kg, 200 mg, or 500 mg prior to exercise testing, either as a single dose or with a 3-day lead-in dose, modestly improves performance endpoints on a cycle ergometer. Improved endpoints included time to exhaustion, peak oxygen use, time to completion, perceived exhaustion, anaerobic capacity, and power (13109,90432,100168). However, in trials in which rhodiola was not taken the morning of testing, or when performance endpoints included forearm endurance or marathon time and recovery, rhodiola 170 mg to 1500 mg daily did not affect perceived exertion, time to exhaustion, or peak oxygen use (15574,19284,90433). A small crossover trial shows that taking 500 mg of rhodiola extract, standardized to 3% rosavins and 1% salidroside, three times daily for 3 days followed by 500 mg 30-minutes before exercise testing increases bench press velocity but decreases bench press repetition volume when compared with placebo (110543). Furthermore, limited evidence suggests that rhodiola extract does not affect muscle strength, speed of limb movement, reaction times, or attention span (13109) but might reduce plasma creatine kinase levels (19284). Also, while some evidence suggests that rhodiola extract can reduce blood lactate levels (19284), other research shows that it increases blood lactate levels after resistance training to a greater degree than placebo (110543). In general, it appears that acute doses of rhodiola may improve specific physical performance parameters, but neither acute nor chronic doses appear to notably improve muscle function. Some research has also assessed rhodiola when used in combination with other ingredients. A small clinical study in trained male cyclists shows that taking a specific combination product (Optygen, First Endurance) containing rhodiola 600 mg (standardized to 3% rosavin and 2.5% salidroside) plus cordyceps 2000 mg (standardized to 7% cordycepic acid), daily for 6 days followed by a half-dose daily for 7 days does not improve time to exhaustion or muscle tissue oxygen saturation when compared with placebo (15573). Additionally, a small crossover study in healthy, recreationally active adult males shows that taking a 30:70 blend of rhodiola and maral root extracts at a dose of 350 mg or 175 mg, ninety minutes prior to isokinetic leg strength exercises, does not influence fatigability, performance variables, or affective responses when compared with placebo (105855).
• Bladder cancer. Although there has been interest in using oral rhodiola for bladder cancer, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral rhodiola for CFS, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Coronavirus disease 2019 (COVID-19). Oral rhodiola extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults a with confirmed history of COVID-19 infection and at least 3 of 9 long COVID-19 symptoms for at least 30 days, but no longer than 3 months, after discharge shows that taking a specific combination product (ADAPT-232/Chisan, Swedish Herbal Institute), containing rhodiola extract 90 mg, schisandra extract 300 mg, and eleuthero extract 78 mg, twice daily for 14 days increases walking duration by around 13 minutes but does not reduce the duration of cough, fatigue, headache, pain, or other respiratory problems when compared with placebo (109635). It is unclear if these findings are due to rhodiola, other ingredients, or the combination.
• Depression. It is unclear if oral rhodiola is beneficial for depression. Details: Clinical practice guidelines from the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Treatments (CANMAT) state that rhodiola is not currently recommended for monotherapy or adjunctive use in major depressive disorder based on mixed evidence (110318). Clinical research shows that taking a specific rhodiola extract (SHR-5, Swedish Herbal Institute) 340 mg once or twice daily reduces symptoms of mild-to-moderate depression after 6 weeks of treatment when compared with placebo. Rhodiola decreased overall depressive symptoms, emotional instability, insomnia, and somatization; however, it did not improve feelings of self-esteem (17616). Another small clinical study in patients with major depressive disorder of moderate severity shows that adding a higher dose of rhodiola 600 mg to sertraline daily for 12 weeks improves depressive symptoms when compared with either sertraline alone or sertraline with a lower dose of rhodiola (300 mg) (102283).
• Diabetes. Although there has been interest in using oral rhodiola for diabetes, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Fatigue. Preliminary clinical research suggests that oral rhodiola extract decreases fatigue in stressful situations. Details: Most preliminary clinical trials have evaluated a specific rhodiola root extract (SHR-5, Swedish Herbal Institute) in various doses and populations. Taking 50 mg of this product twice daily reduces mental fatigue and improves subjective well-being in students during an examination period (1927). Taking 144 mg twice daily for 7 days reduces fatigue, but not stress, in university students (19287). In night shift workers, 170 mg daily for 2 weeks reduces feelings of fatigue and improves mental performance (6877). In military cadets, a single dose of 370-555 mg after 24 hours without sleep improves tests of mental processing and short-term memory (16411). Finally, taking 576 mg daily for 28 days decreases symptoms of fatigue and increases attention, but does not improve quality of life or symptoms of depression, in patients with stress-related fatigue (19286). Other clinical research shows that taking a different rhodiola root extract (Rhodaxon, Teknofarm), 660 mg daily for 20 days, reduces mental fatigue by 30% in first-year university students (19288). Clinical research using another specific dried rhodiola extract (Vitango, Schwabe Pharma) also shows that taking 200 mg twice daily for 12 weeks modestly reduces perceived levels of stress, burnout, and fatigue when compared to baseline in adults experiencing symptoms of burnout. The validity of these findings is limited by the lack of a control group (96459). Rhodiola extract has also been studied in combination schisandra berry extract and Siberian ginseng root extract (ADAPT-232, Swedish Herbal Institute). However, evidence is mixed, with one study showing that 270 mg daily improves attention, accuracy, and speed in tired individuals performing stressful cognitive tasks (19289), and another study showing that 280 mg daily for 7 days does not reduce mental fatigue or stress in university students (19287).
• Generalized anxiety disorder (GAD). It is unclear if oral rhodiola is beneficial for GAD. Details: A small clinical study shows that taking a specific rhodiola extract (Rhodax, Bodyonics Ltd.) 170 mg twice daily for 10 weeks decreases anxiety and depression and improves symptom scores when compared to baseline in patients with GAD (16410). The validity of these findings is limited by the lack of a comparator group.
• Hearing loss. Although there has been interest in using oral rhodiola for hearing loss, there is insufficient reliable information about the clinical effects of rhodiola for this purpose.
• Hyperlipidemia. Although there has been interest in using oral rhodiola for hyperlipidemia, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Menopausal symptoms. Oral rhodiola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients experiencing menopausal symptoms shows that taking a combination product (Menopause Relief EP, EuroPharma USA) containing rhodiola extract 400 mg and black cohosh extract 13 mg daily for 12 weeks improves psychological symptoms of menopause when compared with placebo or black cohosh alone (103269). It is unclear if these findings are due to rhodiola, black cohosh, or the combination.
• Premature ejaculation. Oral rhodiola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with lifelong premature ejaculation shows that taking a specific combination product (EndEP) containing rhodiola 200 mg, folic acid 200 mcg, zinc 10 mg, and biotin 50 mcg once daily for 90 days increases time to ejaculation by about 29 seconds and improves control of ejaculation in about 60% of participants when compared to baseline. These improvements disappear within 90 days of discontinuing treatment. The validity of these findings is limited by the lack of a control group (96460).
• Sexual arousal. Although there has been interest in using oral rhodiola for improving sexual arousal, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Stress. Preliminary clinical research suggests that oral rhodiola extract reduces feelings of stress. Details: Preliminary clinical research in adults with general stress shows that taking a specific dried rhodiola extract (Vitango, Schwabe Pharma) modestly reduces levels of stress in certain situations. Taking 200 mg twice daily before breakfast and lunch for 4 weeks improves stress, disability, and functional impairment when compared to baseline (90431). A small study in college students with anxiety shows that taking 200 mg twice daily for 14 days modestly reduces reported levels of stress, anxiety, anger, confusion, and negative mood when compared to a control group (96462). In adults experiencing symptoms of burnout, taking this specific extract 200 mg twice daily for 12 weeks modestly reduces perceived levels of stress, burnout, and fatigue and improves sexual satisfaction when compared to baseline. The validity of these findings is limited by the lack of a control group (96459). Rhodiola has also been evaluated in combination with other ingredients in individuals with stress. A small clinical study in healthy adults with chronic stress shows that taking a specific combination product (Mg-Teadiola, Sanofi-Aventis), containing rhodiola extract 222 mg, magnesium 150 mg, green tea extract 125 mg (providing theanine 50 mg), vitamin B6 0.7 mg, vitamin B9 0.1 mg, and vitamin B12 1.25 mcg, daily for 4 weeks reduces stress scores when compared with placebo (108672). It is unclear if these findings are due to rhodiola, other ingredients, or the combination.
• Tuberculosis. Although there has been interest in using oral rhodiola for tuberculosis, there is insufficient reliable information about the clinical effects of rhodiola for this condition.
• Upper respiratory tract infection (URTI). Although there has been interest in using oral rhodiola for URTI prevention, there is insufficient reliable information about the clinical effects of rhodiola for this purpose. More evidence is needed to rate rhodiola 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 and appropriately. Cordyceps has been used with apparent safety in doses of 3-6 grams daily for up to 1 year (12,12095,92828,95905,105076,111903).

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

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Tea containing jiaogulan 3 grams has been taken twice daily with apparent safety for up to 3 months (94054,95519,95520). Jiaogulan extract has been used with apparent safety at a dose of up to 450 mg daily for up to 4 months (7069,7070,57056,94058,100961,106651). An in vitro study suggests that low, medium, and high doses of jiaogulan polysaccharides are safe in a model of the human intestinal epithelial barrier (110700).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Ginsenoside Rb1, which is identical to the jiaogulan constituent gypenoside 3, has teratogenic effects in animal models; avoid using (10447).

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately short-term (15). ...when sodium phosphate is used rectally and appropriately, no more than once every 24 hours, short-term (104471). Long-term use or high doses used orally or rectally require monitoring of serum electrolytes (2494,2495,2496,2497,2498,3092,112922). ...when used intravenously. Potassium phosphate is an FDA-approved prescription drug (15).

POSSIBLY UNSAFE ...when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL) of 4 grams daily for adults under 70 years and 3 grams daily for adults older than 70. Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur (7555). ...when used rectally more frequently than once every 24 hours, in excessive doses, with longer retention enema time, or in older patients with comorbidity or renal impairment (112922). The US Food and Drug Administration (FDA) warns that this may increase the risk of hyperphosphatemia, dehydration, and electrolyte imbalances leading to kidney and heart damage (104471).

CHILDREN: LIKELY SAFE
when used orally and appropriately at recommended dietary allowances (RDAs). The daily RDAs are: children 1-3 years, 460 mg; children 4-8 years, 500 mg; males and females 9-18 years, 1250 mg (7555). ...when sodium phosphate is used rectally and appropriately, no more than once every 24 hours, short-term in children 2 years and older (104471). ...when used intravenously. Intravenous potassium phosphate is an FDA-approved prescription drug (15).

CHILDREN: POSSIBLY UNSAFE
when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL) of 3 grams daily for children 1-8 years of age and 4 grams daily for children 9 years and older. Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur (7555). ...when sodium phosphate is used rectally more frequently than once every 24 hours, or in children under 2 years of age or with Hirchsprung disease (112922). The US Food and Drug Administration (FDA) warns that these uses may increase the risk of hyperphosphatemia, dehydration, and electrolyte imbalances leading to kidney and heart damage (104471).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately at the recommended dietary allowance (RDA) of 1250 mg daily for individuals 14-18 years of age and 700 mg daily for those over 18 years of age (7555). ...when sodium phosphate is used rectally and appropriately short-term (15). ...when used intravenously. Intravenous potassium phosphate is an FDA-approved prescription drug (15).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL). Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur. The UL during pregnancy is 3.5 grams daily. During lactation, the UL is 4 grams daily (7555).

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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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POSSIBLY SAFE ...when used orally and appropriately, short-term. There is some clinical research showing that taking rhodiola extract up to 300 mg twice daily has been used without adverse effects for up to 12 weeks (13109,16410,17616,71172,96459,102283,103269).

PREGNANCY AND 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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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cordyceps may increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details In vitro and animal research suggests that cordyceps extract inhibits platelet aggregation and function (3429,46112). However, this interaction has not been reported in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concurrent use of cordyceps might interfere with immunosuppressive therapy.  Details Animal and in vitro research suggests that cordyceps stimulates the immune system (3403,3404,3414,3431,3432). However, limited clinical research suggests that taking cordyceps may lower the necessary therapeutic dose of the immunosuppressant cyclosporine (92828), which suggests that cordyceps may have an immunosuppressive effect.

TESTOSTERONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of cordyceps and testosterone might have additive effects.  Details Animal research suggests that cordyceps can increase testosterone levels (46087). The clinical significance of this finding is unclear.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, jiaogulan might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details In vitro research suggests that jiaogulan has antiplatelet effects (7071).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, jiaogulan might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Clinical research shows that jiaogulan can lower blood glucose levels (94054,95519,95520).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, jiaogulan might decrease the effectiveness of immunosuppressive therapy.  Details Clinical and animal studies suggest that jiaogulan can stimulate the immune system (6,94056).

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BISPHOSPHONATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking phosphate salts with bisphosphonates might increase the risk of hypocalcemia.  Details Combining bisphosphonates and phosphate can cause hypocalcemia. In one report, hypocalcemic tetany developed in a patient taking alendronate (Fosamax) who received a large dose of phosphate salts as a pre-operative laxative (14589).

ERDAFITINIB (Balversa) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = A Taking erdafitinib with phosphate salts increases the risk of hyperphosphatemia.  Details Erdafitinib increases phosphate levels. It is recommended that patients taking erdafitinib restrict phosphate intake to no more than 600-800 mg daily (104470).

FUTIBATINIB (Lytgobi) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = A Taking futibatinib with phosphate salts increases the risk of hyperphosphatemia.  Details Futibatinib can cause hyperphosphatemia, as reported in 88% of patients in clinical studies. In addition, 77% of patients in clinical studies required use of a phosphate binder to manage hyperphosphatemia. Phosphate salts should generally be avoided by people taking this medication (112912).

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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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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking rhodiola with antidiabetes drugs might increase the risk of hypoglycemia.  Details In vitro and animal research shows that rhodiola extract can decrease blood glucose due to alpha-glucosidase activity (15717,15719).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking rhodiola with antihypertensive drugs might increase the risk of hypotension.  Details In vitro and animal research shows that rhodiola extract inhibits angiotensin-converting enzyme (ACE) and might lower blood pressure (15719,19495).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.  Details In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate (96463).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.  Details In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.  Details In vitro research shows that rhodiola inhibits CYP3A4 (19497,96461). This effect is highly variable and appears to be dependent on the rhodiola product studied (96461). However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate (96463).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rhodiola use might interfere with immunosuppressive therapy.  Details In vitro and animal research show that rhodiola has immunostimulatory effects (19498,19499,19500,19501).

LOSARTAN (Cozaar) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Rhodiola might increase the levels and adverse effects of losartan.  Details A clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours (96463).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rhodiola might increase levels of P-glycoprotein substrates.  Details In vitro research shows that rhodiola inhibits P-glycoprotein (19497). Theoretically, using rhodiola with P-glycoprotein substrates might increase drug levels and potentially increase the risk of adverse effects.

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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, cordyceps seems to be generally well tolerated when used for up to 1 year.
Most Common Adverse Effects:
Orally: Abdominal discomfort, constipation, diarrhea.

Gastrointestinal ...Orally, cordyceps has been associated with diarrhea, constipation, abdominal discomfort, dry mouth, and throat discomfort in clinical research. However, these events were uncommon, and in some cases symptoms could be reduced by taking cordyceps after eating (92829,105076,109705).

Hematologic ...Two cases of lead poisoning, characterized by loss of appetite and other symptoms, have been reported for patients taking cordyceps powder. After discontinuing cordyceps supplementation, both patients were treated with chelating agents (46135).

Hepatic ...There is a case report of acute cholestatic hepatitis probably associated with the use of a product containing cordyceps. The 64-year-old male was asymptomatic except for jaundice and laboratory markers and recovered once the supplement was stopped. However, it is unclear whether the hepatitis is associated with the cordyceps or with an unknown contaminant (109704).

Renal ...One case of a mild increase in serum creatinine level (< 30%) has been reported (95905).

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General ...Orally, jiaogulan seems to be well tolerated when used for up to 4 months.
Most Common Adverse Effects:
Orally: Diarrhea and nausea.

Gastrointestinal ...Orally, jiaogulan may cause diarrhea and nausea (6,106651). Dry mouth has also been reported with oral jiaogulan use (106651).

Neurologic/CNS ...Orally, jiaogulan may cause dizziness and insomnia (106651).

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General ...Orally, intravenously, and rectally, phosphate salts are generally well tolerated when used appropriately and/or as prescribed.
Most Common Adverse Effects:
Orally: Abdominal pain, anal irritation, bloating, diarrhea, headache, gastrointestinal irritation, hyperphosphatemia, hypocalcemia, malaise, nausea, sleep disturbance, and vomiting.
Rectally: Hyperphosphatemia and hypocalcemia.
Serious Adverse Effects (Rare):
Orally: Extraskeletal calcification.

Cardiovascular ...Orally, a case of allergic acute coronary syndrome e., Kounis syndrome) is reported in a 43-year-old female after ingesting a specific sodium phosphate laxative product (Travad oral). She presented with maculopapular rash that progressed to anaphylaxis and a non-ST elevation acute coronary syndrome. The patient recovered after hospitalization for 3 days with medical management (112894).

Gastrointestinal ...Orally, phosphate salts can cause gastrointestinal irritation, nausea, abdominal pain, bloating, anal irritation, and vomiting (15,2494,2495,2496,2497,93846,93848,93850,93851,93853,107008). Sodium and potassium phosphates can cause diarrhea (15). Aluminum phosphate can cause constipation (15). A large comparative study shows that, when taken orally as a bowel preparation for colonoscopy, sodium phosphate is associated with gastric mucosal lesions in about 4% of patients (93868).

Neurologic/CNS ...Orally, phosphate salts can commonly cause malaise (93846). Headaches and sleep disturbance may also occur (93848,93851).

Renal ...Orally, use of sodium phosphate for bowel cleansing has been associated with an increased risk of acute kidney injury in some patients (93863). However, a pooled analysis of clinical research suggests that results are not consistent for all patients (93864). Some evidence suggests that female gender, probably due to lower body weight, iron-deficiency anemia, dehydration, and chronic kidney disease are all associated with an increased risk of sodium phosphate-induced kidney dysfunction (93865).

Other ...Orally, phosphate salts can cause fluid and electrolyte disturbances including hyperphosphatemia and hypocalcemia, and extraskeletal calcification. Potassium phosphates can cause hyperkalemia. Sodium phosphates can cause hypernatremia and hypokalemia (15,2494,2495,2496,2497,107008).
Rectally, phosphate salts can cause fluid and electrolyte disturbances including hyperphosphatemia and hypocalcemia (15,112922).
Deaths related to intake of oral or rectal phosphate salts are rare and most have occurred in infants and are related to overdose (93866). However, death has also been reported in elderly patients using sodium phosphate enemas, mainly at standard doses of 250 mL (93867).

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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, rhodiola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, increased or decreased production of saliva.

Gastrointestinal ...Orally, rhodiola extract may cause dry mouth or excessive saliva production (16410,16411).

Neurologic/CNS ...Orally, rhodiola extract can cause dizziness (16410).

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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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