Pregnenolone CRT by Designs for Health

LIKELY INEFFECTIVE

• Alzheimer disease. Lecithin does not improve daily functioning in patients with Alzheimer disease. Details: In patients with Alzheimer disease, taking various types of lecithin, 1.2-45 grams daily for up to 6 months, alone or in combination with various conventional medications, does not improve cognitive function or other measures of disease progression (5149,5151,5152,5156,14817,14823,14825,14837,14838).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral lecithin can slow age-related cognitive decline. Details: A small clinical crossover study in healthy adults aged 64 years and older shows that taking lecithin 26 grams orally daily, alone or in combination with physostigmine, for 5 weeks does not seem to improve memory when compared with placebo (19204).
• Anxiety. Although there is interest in using oral lecithin for anxiety, there is insufficient reliable information about the clinical effects of lecithin for this condition.
• Atopic dermatitis (eczema). Although there is interest in using oral lecithin for atopic dermatitis, there is insufficient reliable information about the clinical effects of lecithin for this condition.
• Bipolar disorder. It is unclear if oral lecithin is beneficial in patients with bipolar disorder. Details: A clinical study in six patients with mania shows that taking lecithin 10 mg three times daily improves symptoms of delusions, incoherent speech, and hallucinations when compared with placebo (14839).
• Dry skin. Although there is interest in using topical lecithin for dry skin, there is insufficient reliable information about the clinical effects of lecithin for this condition.
• Friedreich ataxia. Small clinical studies suggest that oral lecithin is not beneficial in people with Friedreich ataxia. Details: Preliminary clinical research shows that taking lecithin 25 grams orally daily for 1 month does not have any benefit in people with Friedreich ataxia (59298). Other preliminary clinical research shows that taking lecithin for a longer period of 6 months also does not improve performance (19211).
• Hyperlipidemia. Although lecithin may lower cholesterol in healthy people, it does not seem to improve cholesterol levels in people with hyperlipidemia. Details: Some clinical research shows that taking lecithin 20-30 grams daily for up to 11 months decreases cholesterol in healthy people (5147,14820). However, other clinical research shows that lecithin has no effect on low-density lipoprotein cholesterol or total cholesterol levels in people with hyperlipidemia (5148,14820).
• Parkinson disease. It is unclear if oral lecithin is beneficial in patients with Parkinson disease. Details: Preliminary clinical research in patients with Parkinson disease shows that taking lecithin 32 grams daily for 8 weeks does not improve symptoms when compared with placebo (19212).
• Postoperative pain. It is unclear if oral lecithin is beneficial for reducing postoperative pain. Details: Preliminary clinical research shows that taking lecithin 20 grams prior to surgery increases choline levels, but does not reduce postoperative pain after gynecological surgery, when compared with placebo (91231).
• Tardive dyskinesia. It is unclear if oral lecithin is beneficial in patients with tardive dyskinesia. Details: Two small clinical studies in patients with tardive dyskinesia shows that taking lecithin orally for 2 months, alone or in combination with lithium, does not improve symptoms when compared with placebo (14822,14824).
• TPN-associated hepatic steatosis. It is unclear if oral lecithin is beneficial in patients with hepatic steatosis associated with long-term total parenteral nutrition (TPN). Details: A small clinical study in patients on long-term TPN with low choline levels suggests that taking lecithin 20 grams orally twice daily for 6 weeks reduces the degree of hepatic steatosis, compared with no significant changes in those taking placebo (5140).
• Ulcerative colitis. Oral lecithin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a disease-specific medical food (Profermin, Nordisk Rebalance) containing lecithin, fermented oats, barley malt, and lactobacillus plantarum, as 250 mL twice daily for 24 weeks, decreases disease activity by over 56% when compared with baseline and leads to remission in 46% of patients with mild-to-moderate ulcerative colitis (91228). Other preliminary clinical research in this population shows that taking Profermin 250 mL twice daily for 8 weeks improves disease activity and remission rate when compared with another medical food (Fresubin Original, Fresenius Kabi) (90271). The effects of lecithin alone are unclear. More evidence is needed to rate lecithin for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral pregnenolone for aging, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Alcohol use disorder. It is unclear if oral pregnenolone is beneficial in patients with alcohol use disorder. Details: Preliminary clinical research in adults with alcohol use disorder undergoing guided imagery shows that taking pregnenolone 150-250 mg orally twice daily for 8 weeks improves alcohol craving severity scores and anxiety scores when compared with placebo. Taking pregnenolone also improved physiological markers of stress such as heart rate and blood pressure (112726).
• Alzheimer disease. Although there has been interest in using oral pregnenolone for Alzheimer disease, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Autism spectrum disorder. It is unclear if oral pregnenolone is beneficial in patients with autism spectrum disorder. Details: Two small clinical studies show pregnenolone as add-on therapy may improve symptoms in patients with autism spectrum disorder. One small clinical study shows that taking pregnenolone 100 mg orally twice daily as an add-on to risperidone for 10 weeks further improves ratings of irritability, stereotypy, and hyperactivity in drug-naïve adolescents aged 11-17 years with autism when compared with risperidone and placebo (104275). A very small open-label study in adults with autism shows that taking pregnenolone 50-250 mg orally twice daily as an add-on to therapy with psychotropic medications for 12 weeks may improve sensory abnormalities and symptoms of irritability and lethargy (94026). However, the lack of a control group limits the validity of these findings.
• Back pain. It is unclear if oral pregnenolone is beneficial in patients with back pain. Details: One small clinical study in otherwise healthy veterans with chronic low back pain shows that taking pregnenolone orally, titrated up to 500 mg daily, for 4 weeks reduces pain intensity by 0.56 when compared with placebo, as measured on a visual analog scale ranking pain intensity from 0 to 10. This small reduction is not likely to be considered clinically significant. Taking pregnenolone also seemed to modestly reduce the extent that pain interfered with activity or work when compared with placebo; however, there were no significant changes in the other 5 measures of pain interference (104274).
• Bipolar disorder. It is unclear if oral pregnenolone is beneficial in patients with bipolar disorder. Details: Preliminary clinical research in adults with bipolar disorder and depressive episodes shows that taking pregnenolone orally, titrated up to 500 mg daily, as add-on therapy for 12 weeks improves depression symptom scores when compared with placebo (94027).
• Cocaine dependence. It is unclear if oral pregnenolone is beneficial in patients with cocaine dependence. Details: Preliminary clinical research in adults with cocaine dependence undergoing guided imagery shows that taking pregnenolone 150-250 mg orally twice daily for 8 weeks improves cocaine craving severity scores when compared with placebo. Taking pregnenolone also improved physiological markers of stress such as heart rate and blood pressure (112728).
• Coronavirus disease 2019 (COVID-19). Oral pregnenolone has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows in adults with persistent symptoms at least 3 months after a COVID-19 infection shows that taking a combination product containing pregnenolone 40 mg, beta-caryophyllene 40 mg, and other ingredients orally twice daily for 4 weeks improves respiratory and other symptoms when compared with baseline (112727). The validity of this study is limited by the lack of a comparator group. It is unclear if this effect is due to pregnenolone, other ingredients, or the combination.
• Critical illness (trauma). Although there has been interest in using oral pregnenolone for trauma, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Depression. Although there has been interest in using oral pregnenolone for depression, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Endometriosis. Although there has been interest in using oral pregnenolone for endometriosis, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Fatigue. Although there has been interest in using oral pregnenolone for fatigue, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Fibrocystic breast disease. Although there has been interest in using oral pregnenolone for fibrocystic breast disease, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Memory. Although there has been interest in using oral pregnenolone for memory, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Menopausal symptoms. Although there has been interest in using oral pregnenolone for menopausal symptoms, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Multiple sclerosis (MS). Although there has been interest in using oral pregnenolone for MS, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Premenstrual syndrome (PMS). Although there has been interest in using oral pregnenolone for PMS, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Psoriasis. Although there has been interest in using oral pregnenolone for psoriasis, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Schizophrenia. It is unclear if oral pregnenolone is beneficial in patients with schizophrenia. Details: The effects of pregnenolone adjunctive therapy on negative symptoms of schizophrenia are conflicting. Several clinical studies in patients with schizophrenia and schizoaffective disorder and suboptimal response to previous antipsychotic treatments show that taking pregnenolone 50 mg orally daily alone or as add-on therapy with L-theanine 400 mg daily, for 8 weeks, reduces negative symptoms based on the negative symptom scale of the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) when compared with placebo (94029,97923). However, conflicting results exist. One study shows that taking pregnenolone 30 mg or 200 mg daily for 8 weeks does not improve negative symptoms based on the negative symptom scale of the PANSS in patients with schizophrenia and schizoaffective disorder (94028). Furthermore, another clinical study conducted in women hospitalized with an acute episode of schizophrenia shows that taking pregnenolone 50 mg orally daily for 8 weeks in combination with risperidone 2-6 mg daily does not reduce negative symptoms when compared with risperidone plus placebo (97924). Reasons for the conflicting results may relate to concomitant use of psychotropic medications such as mood stabilizers and antidepressants, prenenolone dosage, and schizophrenia subtypes of the included patients. Despite some conflicting results (94028), most research shows that taking pregnenolone orally as adjunctive therapy does not significantly improve positive symptoms based on the positive symptom subscale of the PANSS compared to placebo in patients with schizophrenia and schizoaffective disorder (94029,94032,97923,97924). One clinical study shows that taking pregnenolone 50 mg orally daily for 8 weeks in combination with antipsychotics might improve visual attention but does not appear to improve other neurocognitive symptoms of schizophrenia such as deficits in sustained attention or executive function compared with placebo (97925).
• Scleroderma. Although there has been interest in using oral pregnenolone for scleroderma, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Seizures. Although there has been interest in using oral pregnenolone for seizures, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Systemic lupus erythematosus (SLE). Although there has been interest in using oral pregnenolone for SLE, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose.
• Stress. Although there has been interest in using oral pregnenolone for stress, there is insufficient reliable information about the clinical effects of pregnenolone for this purpose. More evidence is needed to rate pregnenolone 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. Lecithin has Generally Recognized As Safe (GRAS) status in the US (2619,105544). ...when used orally and appropriately in medicinal amounts. Lecithin has been used safely in doses of up to 30 grams daily for up to 6 weeks (5140,5149,5152,5156,14817,14822,14838,19212). ...when used topically (4914).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts. Lecithin has Generally Recognized As Safe (GRAS) status in the US (105544). There is insufficient reliable information available about the safety of medicinal amounts of lecithin during pregnancy or lactation; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately, short-term. Pregnenolone has been used safely for up to 12 weeks, with doses titrated up to 500 mg daily (94026,94027,97923,104274). There is insufficient reliable information available about the safety of pregnenolone when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Pregnenolone has been used safely for up to 10 weeks at doses of 200 mg daily in adolescents aged 11-17 years (104275). There is insufficient reliable information available about the safety of pregnenolone in younger children or when used orally for longer durations.

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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BENZODIAZEPINES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant use of pregnenolone may reduce the effects of benzodiazepines.  Details Very preliminary clinical research shows that chronic use of pregnenolone reduces sedative effects of diazepam when compared with chronic use of placebo. This effect may be related to the activity of pregnenolone at GABAA receptors (94031).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of estrogens.  Details Pregnenolone is a precursor for several steroid hormones, including estrogens (3008).

PROGESTERONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of progesterone.  Details In humans, some research shows that oral administration of pregnenolone can increase levels of progesterone (94032). However, other research shows no effect on progesterone levels (94028). It is possible the impact of pregnenolone on progesterone levels may be dose dependent.

PROGESTIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of progestin.  Details Pregnenolone is a precursor for several steroid hormones, including progestin (3008).

TESTOSTERONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pregnenolone might enhance the effects of testosterone.  Details Pregnenolone is a precursor for several steroid hormones, including testosterone (3008). However, preliminary clinical research shows that taking pregnenolone 30-500 mg orally daily for up to 8 weeks does not affect testosterone levels (94028,94032).

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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, lecithin is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, fullness, and nausea.

Dermatologic ...Orally, lecithin can cause allergic skin reactions in people with egg or soy allergies (15705).

Gastrointestinal ...Orally, lecithin may cause abdominal pain, diarrhea, fullness, and nausea (5140,6243,14817,14822,14838,19204,59281).

Neurologic/CNS ...Orally, lecithin caused CNS complaints and agitation in one patient in a clinical trial (59261).

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General ...Orally, pregnenolone is generally well tolerated.
Most Common Adverse Effects:
Orally: Acne, agitation, diarrhea, drowsiness, excitement, hair loss, skin abscess, sweating, tremor.

Cardiovascular ...A case of palpitations has been reported after oral use of pregnenolone (94031).

Dermatologic ...Orally, pregnenolone has been reported to cause skin abscesses, acne, and hair loss (94027,94031). A case of skin rash accompanied by a burning sensation on the back and sides of the hands has also been reported with oral pregnenolone use, possibly related to a photosensitivity reaction. The rash cleared on its own (94031).

Gastrointestinal ...Orally, pregnenolone may cause diarrhea. Constipation has also been reported after oral use; however, it is not certain if this effect was due to pregnenolone (94026).

Musculoskeletal ...A case of muscle pain/stiffness has been reported after oral use of pregnenolone (94032).

Neurologic/CNS ...Orally, pregnenolone has been reported to cause restlessness, tiredness, sweating, and a case of cold extremities (94026,94032). Sleep problems, drowsiness, and tremor have also been reported; however, it not certain if these effects were due to pregnenolone (94026,94031).

Psychiatric ...Orally, pregnenolone has been reported to cause depressive affect and increased appetite (94026,94031). Increased excitement, agitation, increased motor activity, and anorexia have also been reported; however, it is not certain if these effects were due to pregnenolone (94026).

Pulmonary/Respiratory ...A case of sinusitis has been reported after oral use of pregnenolone (94027).

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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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