Morphobolic by Morphogen Nutrition

There is insufficient reliable information available about the effectiveness of laxogenin.

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POSSIBLY EFFECTIVE

• Memory. Oral rosemary seems to improve memory in young adults. It is unclear if rosemary aromatherapy improves memory. Details: Clinical research in healthy adults shows that taking rosemary 500 mg orally twice daily for one month improves memory by approximately 14% when compared with placebo (98536). Other preliminary clinical research shows that applying four drops of pure rosemary essential oil (Tisserand Aromatherapy) to an aromatherapy diffuser pad 5 minutes before a single test period can improve the quality, but not the speed, of memory recall, and increase alertness and contentment more than lavender aromatherapy or no aroma (18323). Rosemary aromatherapy has also been evaluated for improving memory in adults with kidney failure. A small clinical study in patients (mean age 53 years) undergoing hemodialysis shows that aromatherapy with rosemary essential oil three times weekly for 1 month does not improve medication adherence or measures of prospective and retrospective memory when compared with a control group. In this study, five drops of rosemary essential oil were applied to gauze, which was then placed 10 cm from the patient's nose for 30 minutes starting 1 hour after hemodialysis (109559).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Abortion. Although there has been interest in the use of oral rosemary as an abortifacient, there is insufficient reliable information about the clinical effects of rosemary for this purpose.
• Age-related cognitive decline. It is unclear if oral rosemary is beneficial for age-related cognitive decline. Details: A small clinical study in healthy individuals aged 65-90 years shows that a single 750 mg dose of powdered rosemary leaf in tomato juice may improve memory speed. However, higher single doses of 1500-6000 mg seem to have a deleterious effect on memory speed. For other measures of attention and memory, there were no clear benefits across the range of doses from 750-6000 mg (18246). Oral rosemary has also been evaluated in combination with other ingredients. A small clinical study in healthy adults aged 62 years or younger shows that taking a combination product containing equal parts rosemary, lemon balm, and sage twice daily for 2 weeks modestly improves word recall when compared with placebo. However, it does not appear to have benefit in adults aged 63 years and older (97277). It is unclear if any benefit is due to rosemary, other ingredients, or the combination.
• Alopecia areata. Topical rosemary oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rosemary oil 114 mg, in combination with lavender oil 108 mg, thyme oil 88 mg, and cedarwood oil 94 mg, mixed with jojoba oil 3 mL and grapeseed oil 20 mL and applied topically to the scalp, improves hair growth in 44% of patients, compared with 15% of those receiving placebo. This combination was massaged into the scalp for a minimum of 2 minutes, followed by wrapping the head in a warm towel, every night for 7 months (5177).
• Androgenic alopecia. It is unclear if topical rosemary is beneficial for androgenic alopecia. Details: Preliminary clinical research shows that applying rosemary oil (Barij Essence Pharmaceutical Company) 1 mL to the scalp twice daily for 6 months is as effective as minoxidil 2% for increasing hair count in patients with androgenic alopecia (91729).
• Depression. It is unclear if oral rosemary is beneficial for major depressive disorder. Details: A small clinical trial among adults newly diagnosed with major depressive disorder and recent initiation of antidepressant medication shows that taking rosemary dried leaf extract 650 mg twice daily for 8 weeks might reduce some symptoms of depression and anxiety when compared with placebo (112141). However, the validity of these findings is limited by differences in baseline depression symptom scores between groups.
• Diabetes. It is unclear if oral rosemary is beneficial for improving glycemic control in patients with type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that taking rosemary tea daily for 90 days decreases glycated hemoglobin levels by 15% and waist and hip circumference by 6% and improves insulin resistance. However, there was no effect on fasting blood glucose, lipid profile, body weight, or body mass index (BMI). The tea was made by adding rosemary 2 grams to a liter of boiling water for 3 minutes and then passing through a sieve (105323). Other preliminary clinical research in adults with type 2 diabetes shows that taking rosemary powder 3 grams daily for 4 weeks does not reduce fasting blood glucose levels or improve lipid profile when compared with baseline. These endpoints were improved in a group of healthy adults (105327). The validity of the findings from these studies is limited by the lack a comparator group.
• Diabetic nephropathy. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product (Canephron N, Bionorica) containing 18 mg each of rosemary leaf, centaury herb, and lovage root per tablet, as two tablets three times daily for 6 months along with standard antidiabetes treatment and enalapril (Vasotec), decreases microalbuminuria by 73%, decreases albumin:creatinine ratio by 46%, increases high-density lipoprotein (HDL) cholesterol by 25%, and lowers triglyceride levels by 43%, but does not improve glomerular filtration rate, when compared to baseline. Improvements were greater in those taking the combination product than in those treated only with standard antidiabetes therapy and enalapril. However, the combination product does not appear to improve reductions in total cholesterol or low-density lipoprotein (LDL) cholesterol (91726).
• Dysmenorrhea. It is unclear if oral rosemary is beneficial for dysmenorrhea. Details: In patients with moderate primary dysmenorrhea, clinical research shows that taking rosemary extract 220 mg every 8 hours for the first three days of the menstrual cycle, repeated for two menstrual cycles, is as effective as mefenamic acid for reducing average pain and bleeding when compared with two baseline cycles (105328).
• Fatigue. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy young adults with below-average energy levels shows that taking a single dose of a mixture of rosemary from Albania (Rosmarinus officinalis) and Morocco (Rosmarinus eriocalyx) 1.7 grams does not consistently improve sustained attention, motivation to perform cognitive tasks, mental energy, or mental fatigue when compared with placebo (91731).
• Fibromyalgia. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with fibromyalgia shows that taking an oral product containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (Meta050, Metagenics), at a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks, does not improve symptoms when compared to baseline (18327).
• Gingivitis. A mouth rinse containing rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with 10 mL of mouthwash containing 5% v/v of a combined alcoholic extract of rosemary, calendula, and ginger for 30 seconds twice daily after meals for 2 weeks decreases plaque formation, gingival inflammation, and gingival bleeding similarly to chlorhexidine gluconate 0.2% mouthwash and better than a placebo mouthwash (93555).
• Hypertension. Although there is interest in using oral rosemary for hypertension, there is insufficient reliable information about the clinical effects of rosemary for this condition.
• Hypotension. It is unclear if oral rosemary is beneficial for hypotension. Details: Preliminary clinical research in patients with primary hypotension shows that taking rosemary essential oil (Metapharmaceutical) 1 mL every 8 hours for 44 weeks increases systolic blood pressure by 13 mmHg and diastolic blood pressure by 7 mmHg when compared to baseline. However, blood pressure returned to near baseline values after treatment discontinuation (91730).
• Mental alertness. It is unclear if rosemary aromatherapy is beneficial for improving mental alertness. Details: Preliminary clinical research in nurses working on a night shift shows that placing one drop of rosemary oil on a surgical mask that is worn for 2 hours with a 10-minute on/15-minute off cycle modestly increases alertness and reduces sleepiness when compared with a water drop control (105324).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral rosemary leaf is beneficial in patients with NAFLD. Details: A small clinical study in patients with NAFLD shows that taking rosemary leaf powder 2 grams twice daily for 8 weeks, in conjunction with diet and exercise recommendations, does not improve measures of liver function, glycemic control, cholesterol, or body weight when compared with placebo (109561).
• Opioid withdrawal. It is unclear if oral rosemary is beneficial for opioid withdrawal when used in combination with methadone. Details: Preliminary clinical research shows that taking rosemary leaf along with methadone for 2 weeks improves symptoms of opioid withdrawal and the ability to sleep when compared with methadone alone after 3 and 7 days of treatment, but not after 2 weeks. Rosemary leaf was provided in capsules containing 300 mg each (Barij Essence Pharmaceutical Company) at a dose of 16 capsules daily for the first 3 days, 12 capsules daily for the next 4 days, and eight capsules daily for the next 7 days, in divided doses (91727).
• Osteoarthritis. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective reductions in pain associated with osteoarthritis when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Raynaud syndrome. It is unclear if topical rosemary essential oil is beneficial in patients with Raynaud syndrome. Details: A very small, open-label study in patients with Raynaud syndrome caused by systemic scleroderma shows that applying 10 drops of rosemary 10% essential oil to the hands does not increase skin temperature or improve warmth perception when compared with olive oil (109560). However, this study may have been inadequately powered to detect a difference between groups.
• Rheumatoid arthritis (RA). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective decreases in pain associated with RA when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
• Stress. It is unclear if rosemary aromatherapy is beneficial for stress. Details: Preliminary clinical research on the use of rosemary aromatherapy for anxiety and stress is conflicting. In a group of graduate nursing students, perceived stress associated with taking a test was lower when inhalers containing rosemary or lavender oil were used. Three drops of rosemary essential oil were added to an inhaler and inhaled before and during the test. Pulse rates, but not blood pressure, were also reduced (18324). In contrast, a small clinical study in adults aged 18-30 years shows that the aroma from diluted rosemary essential oil applied to the wrist during timed crossword puzzle completion actually increases subjective feelings of anxiety and tension when compared with placebo (18325).
• Sunburn. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of rosemary and grapefruit extracts in a 1:1 ratio (NutroxSun, Monteloeder, Inc.), 250 mg orally once daily for 12 weeks, increases the amount of UV radiation needed to cause sunburn by 34% after 8 weeks and 56% after 12 weeks when compared to baseline (91728). The validity of these findings is limited by the lack of a comparator group.
• Upper respiratory tract infection (URTI). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial among healthy adults shows that taking a combination product containing rosemary leaf extract, aloe gel powder, and poria mushroom extract daily for 8 weeks does not reduce the frequency, duration, or severity of URTI-related symptoms when compared with placebo. However, in patients receiving an influenza vaccine midway through the study, this product does seem to improve some immune response biomarkers when compared with placebo (111921). The amount of rosemary leaf extract in the supplement was not disclosed.
• Wound healing. It is unclear if topical rosemary cream is beneficial for wound healing. Details: A moderate-sized clinical trial among primiparous adults with medio-lateral episiotomy shows that applying a cream containing rosemary extract to the wound twice daily for 10 days improves episiotomy wound healing and reduces redness and discharge when compared with placebo cream (112143). More evidence is needed to rate rosemary 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 used orally. Although the safety of purified laxogenin, or its synthetic analogue 5-alpha-hydroxy laxogenin, has not been studied in clinical trials, products labeled as containing either of these ingredients are often contaminated with prohibited compounds. Some products have been shown to contain potentially unsafe ingredients such as arimistane, dehydroepiandrosterone (DHEA), and testosterone phenylpropionate (99191).

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

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LIKELY SAFE ...when used orally in amounts typically found in foods. Rosemary has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when the leaf is used orally and appropriately in medicinal amounts (18). Powdered rosemary leaf has been used with apparent safety as a single dose of up to 1.5 grams (18246,91731) or at a dose of 1-4 grams daily for up to 8 weeks (91727,98536,105327,109561). ...when the essential oil is used topically and appropriately for up to 7 months (5177,91729,109560). ...when the essential oil is used by inhalation as aromatherapy, short-term (7107,18323,105324,109559).

LIKELY UNSAFE ...when the essential oil or very large quantities of rosemary leaf are used orally. Ingestion of undiluted rosemary oil or very large quantities of rosemary leaf can cause serious adverse effects (18,515).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Rosemary might have uterine and menstrual flow stimulant effects (4,12,18), and might increase metabolism of estradiol and estrone (18331); avoid using. There is insufficient reliable information available about the safety of rosemary when used topically during pregnancy.

LACTATION:
There is insufficient reliable information available about the safety of using rosemary in medicinal amounts during lactation; 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 = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details In vitro and animal research suggests that rosemary inhibits platelet aggregation (18334,18335,18336,18337).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models (71821,71923). However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults (105327), no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs (105323,105327).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.  Details Rosemary is reported to contain salicylates (18330).

CHOLINE MAGNESIUM TRISALICYLATE (Trilisate) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.  Details Rosemary is reported to contain salicylate (18330).

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A1 substrates.  Details In vitro research shows that rosemary induces CYP1A1 enzymes (18332,18333). This effect has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research shows that rosemary induces CYP1A2 enzymes (18332,18333). This effect has not been reported in humans.

SALSALATE (Disalcid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.  Details Rosemary is reported to contain salicylate (18330).

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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 ...There is currently a limited amount of information available about the adverse effects of laxogenin. Products labeled as containing laxogenin or 5-alpha-hydroxy laxogenin might contain contaminants, including prohibited compounds (99191).

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General ...Orally, rosemary seems to be well tolerated when used in appropriate medicinal amounts. Undiluted rosemary oil or very large quantities of rosemary leaf should not be consumed. Topically and as aromatherapy, rosemary seems to be well tolerated.

Dermatologic ...Topically, rosemary use can lead to photosensitivity, erythema, dermatitis, and cheilitis in hypersensitive individuals (4,6).

Immunologic ...Topically, allergic reactions can occur. When used in the mouth, lip and gum edema have occurred (101173). When used on the skin, allergic contact dermatitis has occurred, likely due to the constituent carnosol (71715,71924,71926).
Rosemary might also cause occupational asthma. A case of occupational asthma caused by several aromatic herbs including thyme, rosemary, bay leaf, and garlic has been reported. The diagnosis was confirmed by inhalation challenges. Although all of the herbs caused immediate skin reactivity, a radioallergosorbent test (RAST) showed that garlic was the most potent allergen by weight, with rosemary and the other herbs showing less reactivity (783).

Neurologic/CNS ...Orally, the undiluted oil, as well as the camphor constituent of rosemary, might cause seizures (4,5,6,12868).

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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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