Probiotic Gummies Mixed Berry [Discontinued] by Culturelle

POSSIBLY EFFECTIVE

• Constipation. Most clinical research shows that oral inulin modestly improves stool frequency, but may not improve discomfort, in adults and children with constipation. Details: A meta-analysis of clinical research in adults with constipation shows that consuming inulin improves stool frequency by approximately 0.7 stools per week. It also seems to improve stool transit time, consistency, and hardness, but does not reduce pain or bloating (93718). Additional clinical research shows that taking a specific type of inulin (OraftiGR, BENEO GmbH) 12 grams daily in three divided doses for 4 weeks increases stool frequency by approximately one stool per week when compared with a maltodextrin control. Taking inulin also reduces the number of patients experiencing hard and lumpy stools by 13%, but does not improve symptoms of bloating, distension, physical discomfort, or gas (96850). In children aged 2-5 years, one small clinical study shows that taking a specific combination of two inulin products (Orafti P95 oligofructose and Orafti GR inulin, BENEO GmbH), 2 grams twice daily in a dairy liquid for 6 weeks, improves the softness of stools, but not pain with stooling or stool frequency, when compared with a maltodextrin control (96848). Research in older adults is conflicting. One small study shows that taking inulin 20-40 grams daily for 19 days increases the number of stools from 1-2 per week to 8-9 per week (10415). However, other preliminary clinical research in this population shows that taking a specific inulin supplement (Fibruline Instant, Cosucra Groupe Warcoing) 15 grams daily in yogurt or stewed fruit for 4 weeks does not improve bowel symptoms, stool frequency, or stool consistency (93724).
• Diabetes. Short-term use of oral inulin along with antidiabetes drugs may improve glycemic control in some patients with type 2 diabetes; however, the benefits of long-term use are unclear. Details: Two meta-analyses of clinical research in normal weight and obese patients with type 2 diabetes show that taking inulin 0.8-10 grams orally daily for 6-12 weeks reduces glycated hemoglobin (HbA1c) by 0.65% and fasting plasma glucose by 16 mg/dL when compared with control. Taking inulin also improved HOMA-IR, a measure of insulin resistance, when compared with control. Researchers did not evaluate the most effective dose of inulin; however, most studies used 8.4-10 grams daily (103198,105533). In females treated with metformin and glyburide, taking inulin 10 grams daily for 8 weeks reduces fasting blood glucose by 15 mg/dL and HbA1c by 1% when compared with placebo (93719). Population research in adults has also found that high dietary intake of inulin over 8 years of follow up is associated with a 6% lower risk of type 2 diabetes when compared with low dietary intake (110515). Inulin has also been studied in combination with other supplements. Preliminary clinical research in elderly patients with diabetes shows that drinking a milk powder product supplemented with inulin and resistant dextrin 30 grams before breakfast and 15 grams before dinner for 12 weeks decreases fasting plasma glucose by 17 mg/dL, HbA1c by 0.38%, postprandial glucose by 27 mg/dL, body weight by 0.8 kg, and systolic and diastolic blood pressure by 5 mmHg when compared with placebo (99843). Other clinical research in adults with type 2 diabetes shows that taking a specific combination product (Orafti Synergy1, BENEO GmbH), containing 50% inulin and 50% fructo-oligosaccharides, 8 grams orally twice daily for 6 weeks does not reduce body weight or caloric intake or increase satiety scores when compared with placebo (107934).
• Obesity. Oral inulin might modestly improve short-term weight loss. Additional research is needed to determine the long-term effects of inulin on weight loss and weight maintenance in overweight or obese individuals. Details: Some clinical research in overweight and obese females with diabetes shows that taking inulin 10 grams daily for 8 weeks results in weight loss of 2.6 kg, compared with no weight loss in those taking placebo (93719). Preliminary clinical research in overweight or obese patients with prediabetes shows that taking a specific brand of inulin (Orafti Synergy 1, BENEO GmbH) 30 grams orally daily for 6 weeks reduces body weight by 0.4 kg, compared with a 0.4 kg increase in those in the control group (93721). Preliminary clinical research in adults with obesity shows that taking inulin 16 grams orally daily for 3 months moderately reduces body weight and body mass index (BMI) when compared with placebo. However, these effects were most prominent in subjects that also increased physical activity (110514). Additional preliminary clinical research in adults with overweight shows that adding 18 grams of inulin powder to green tea daily increases weight loss when compared with green tea alone. Over six weeks, individuals taking inulin lost 2 kg, compared with no weight loss in those taking green tea. Weight loss was maintained for at least 2 weeks (93726). Clinical trials in children show conflicting results. In children aged 7-12 years, a small clinical study shows that taking a specific oligofructose-enriched inulin product (Orafti Synergy1, BENEO GmbH) 8 grams orally in water before one meal daily for 16 weeks decreases weight gain by 2.4-fold and attenuates an increase in BMI when compared with placebo (96847). However, other preliminary clinical research in children with obesity aged 7-15 years shows that taking inulin extract 13 grams orally daily for 6 months does not reduce body weight or BMI when compared with placebo (110598). However, other clinical research shows that taking inulin orally in combination with other ingredients might not improve weight loss. Combining inulin, chromium picolinate, capsicum, L-phenylalanine, and other nutrients with caloric reduction and exercise doesn't seem to reduce weight in moderately obese patients when compared to caloric reduction and exercise alone (7607). Another preliminary clinical trial shows that taking inulin 10 grams with maltodextrin 10 grams daily for 12 weeks does not reduce body weight or improve body composition when compared with placebo in adults with overweight or obesity following a calorie-restricted diet (103202). Preliminary clinical research in adults with obesity also shows that consuming a seafood-based dietary product fortified with inulin 1.7 grams, fish oil 370 mg (containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and bifidobacterium animalis daily for 12 weeks does not lower body weight, waist circumference, abdominal fat, serum cholesterol levels, or blood pressure when compared with placebo. However, consuming the product modestly improved some markers of insulin resistance (110600).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. It is unclear if oral inulin is beneficial in patients with alcohol use disorder. Details: Preliminary clinical research in adults with alcohol use disorder who were recently admitted to the hospital shows that taking a specific inulin product (Fibruline, Cosucra) 4-16 grams orally daily for 17 days does not improve liver function tests when compared with placebo. Some liver function tests were also worse in those treated with inulin (110601).
• Antibiotic-associated diarrhea. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 6 months to 14 years receiving antibiotics for common infections shows that taking a combination of inulin and fructo-oligosaccharides, up to 5 grams daily depending on age, does not reduce the rate of antibiotic-associated diarrhea (93720).
• Celiac disease. Small clinical studies suggest that patients with celiac disease who take oral inulin may have a lower risk of vitamin and mineral deficiency. Details: Preliminary clinical research in a small number of children and adolescents with vitamin and mineral malabsorption due to celiac disease shows that taking a specific oligofructose-enriched inulin product (Orafti Synergy 1, BENEO GmbH) 10 grams daily for 3 months improves the absorption of vitamin D, vitamin E, and iron, but not vitamin A (99841,99842). Levels of 25-hydroxy vitamin D and vitamin E increased by 42% and 19%, respectively, compared with no significant improvements in those taking placebo (99842). Although taking inulin did not improve serum ferritin levels, it did decrease serum hepcidin concentrations by 61% when compared with baseline, while no significant improvement was reported with placebo. Hepcidin is a regulator of iron homeostasis, and increased levels are associated with iron-deficiency anemia (99841).
• Child growth. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy, exclusively formula-fed, infants less than 4 months of age shows that supplementing formula with 0.8 grams/dL of a specific combination product (Orafti Synergy1, Beneo-Orafti) containing 50% inulin and 50% fructo-oligosaccharide until 12 months of age does not improve markers of child growth, including body weight, length, and head circumference, when compared with placebo. The combination product was associated with a reduced duration of fever during infectious episodes, but not with a reduction in the number of infections. It is unclear if any potential effects are due to inulin, fructo-oligosaccharide, or the combination (107937).
• Chronic kidney disease (CKD). It is unclear if oral inulin is beneficial in patients with CKD. Details: In adults with CKD, adding inulin 19 grams daily for 6 months to a low-protein diet reduces serum insulin, fasting plasma glucose, total serum cholesterol, triglycerides, and markers of systemic inflammation, while increasing serum high density lipoprotein (HDL) cholesterol, when compared with baseline (105534). However, it is unclear if similar changes occur with a low-protein diet alone, or if the rate of progression of CKD is reduced. Population research in adults has found that high dietary intake of inulin over 8 years of follow up is not associated with a lower risk of CKD when compared with low dietary intake (110515).
• Hypercholesterolemia. It is unclear if oral inulin reduces cholesterol levels in patients with hypercholesterolemia. Details: Research in patients with hypercholesterolemia has shown mixed results, with some studies showing a small decrease and others showing no improvement in serum cholesterol levels (7604,8450,10412,10413,96849). A typical dose of inulin used is 6 grams orally three times daily for up to 6 weeks (10412). A meta-analysis of healthy, dyslipidemic, overweight or diabetic patients shows that inulin reduces levels of low-density lipoprotein (LDL) cholesterol by approximately 5% (96849). Another meta-analysis of randomized clinical trials in the same population shows that taking inulin 1.5-30 grams daily for 2-12 weeks reduces LDL cholesterol levels by 7 mg/dL and increases high-density lipoprotein cholesterol levels by 2 mg/mL when compared with control. However, this meta-analysis also included data from patients treated with fructo-oligosaccharides instead of inulin (107940).
• Hypertension. It is unclear if oral inulin is beneficial in patients with hypertension. Details: Population research in adults has found that high dietary intake of inulin over 8 years of follow up is associated with a 21% lower risk of hypertension when compared with low dietary intake (110515).
• Hypertriglyceridemia. It is unclear if oral inulin is beneficial in patients with hypertriglyceridemia. Details: A meta-analysis of clinical trials in normal and moderately hyperlipidemic patients suggests that taking inulin-type fructans at an approximate average dose of 14 grams daily reduces triglyceride levels by about 15 mg/dL when compared with control (93737). However, other research, including a meta-analysis of healthy, dyslipidemic, overweight or diabetic patients shows that taking inulin 1.5-30 grams daily for 2-12 weeks does not reduce triglyceride levels when compared with control. However, these negative studies are limited by small sample sizes and inclusion of data from patients treated with fructo-oligosaccharides instead of inulin (7604,107940).
• Impaired glucose tolerance (prediabetes). Several small clinical studies suggest that oral inulin is not beneficial in patients with prediabetes. Details: Preliminary clinical research in adults with prediabetes shows that taking inulin 15 grams orally daily for 24 weeks does not improve fasting blood glucose, glycated hemoglobin (HbA1c), or lipid levels when compared with placebo. However, taking inulin modestly improved markers of insulin resistance (107938). Two other, small, clinical trials show that taking specific inulin products (Orafti Synergy 1, BENEO GmbH or Frutafit IQ, Sensus American) 10-30 grams daily for 6 weeks does not improve blood glucose, insulin resistance, glucose homeostasis, or insulin sensitivity when compared with placebo (93721,107936). However, these studies may have been inadequately powered to detect a difference between groups.
• Iron deficiency anemia. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in young adult females with iron deficiency anemia shows that taking inulin 963 mg/kg and iron supplementation orally daily for 3 months modestly improves serum hemoglobin, hematocrit, and iron levels when compared with a control group consuming iron-fortified flour (110599).
• Menopausal symptoms. It is unclear if oral inulin is beneficial in patients with hypertriglyceridemia. Details: Preliminary clinical research in adults experiencing menopause shows that consuming yogurt enriched with a specific inulin (Frutafit TEX, Sensus Company) 1.5% daily for 6 weeks moderately improves menopausal symptom scores, including depression, anxiety, and vasomotor symptoms, when compared with yogurt alone (107659).
• Nonalcoholic fatty liver disease (NAFLD). Taking oral inulin alone does not seem to improve liver transaminase levels in patients with NAFLD. Details: Preliminary clinical research in patients with NAFLD shows that taking metronidazole 400 mg twice daily for one week plus inulin 4 grams twice daily for 12 weeks reduces levels of alanine aminotransferase and aspartate aminotransferase when compared with placebo. However, when inulin is taken without metronidazole, these measures are not improved (103200).
• Polycystic ovary syndrome (PCOS). It is unclear if oral inulin is beneficial in patients with PCOS. Details: Preliminary clinical research in overweight or obese females with PCOS shows that taking specific products containing inulin (FrutaFit TEX, Sensus American) or inulin and fructo-oligosaccharides (FrutaFit IQ, Sensus American) 10 grams orally once daily for 12 weeks does not reduce systolic or diastolic blood pressure when compared with placebo. However, the validity of this study is limited by the inclusion of subjects with and without hypertension at baseline (107941). More evidence is needed to rate inulin 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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LIKELY SAFE ...when used orally in amounts commonly found in foods. Inulin has Generally Recognized As Safe status (GRAS) in the US (93728).

POSSIBLY SAFE ...when used orally and appropriately in supplemental doses, short-term. Doses of 8-18 grams daily have been used safely for up to 24 weeks (7604,7605,7606,7607,8451,93716,93719,93726,103200,107936,107935,107938). Also, 20 grams daily has been used with apparent safety for up to 3 weeks (96836,96850). There is insufficient reliable information available about the safety of inulin when used long-term.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods. Inulin has Generally Recognized As Safe status (GRAS) in the US (93728).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in supplemental doses, short-term. Clinical studies have used doses of 3-6 grams daily for 10 days in children 3-6 years of age and 5-13 grams daily for up to 6 months in children 7-15 years of age with apparent safety (96847,110598,110602). ...when used in infant formula. A formula containing chicory fructans (Orafti Synergy1, BENEO GmbH), approximately 50% of which were inulin, has been used with apparent safety in infants for 8-12 months (93717,107937).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (93728). There is insufficient reliable information available about using inulin in medicinal amounts during pregnancy or lactation; avoid use.

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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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ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, inulin might increase the risk of hypoglycemia with antidiabetes drugs.  Details Some clinical research shows that inulin improves glycemic control in patients with diabetes; however, it is unclear if it has hypoglycemic effects (93719,99843,103198).

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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, inulin is well tolerated.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, flatulence, and gastrointestinal cramps.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis has occurred following consumption of foods high in inulin.

Gastrointestinal ...Orally, inulin may cause flatulence, bloating, diarrhea, constipation, and gastrointestinal cramps, especially at doses over 30 grams (7604,8450,8509,93716,93721,93724,96836,96850,96851,99843)(107936,107940,107941,110602).

Immunologic ...Severe allergic reactions to inulin-containing foods have been reported. There is one report of anaphylaxis following consumption of foods with a high concentration of inulin including salsify, artichoke leaves, and margarine (7608).

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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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