Pregnenolone Drops by Energetix

LIKELY EFFECTIVE

• Vaginal atrophy. Intravaginal DHEA can reduce pain during intercourse and improve vaginal health in patients with this condition. Details: Clinical research shows that ovules or suppositories containing DHEA 0.25% to 1%, inserted vaginally once daily for 12 weeks, can reverse vaginal thinning, restore vaginal pH, and reduce pain during sexual intercourse by up to 15% when compared with placebo in patients with vaginal atrophy (21320,21429,21430,94576). A specific vaginal insert containing DHEA 0.5% (Intrarosa, Endoceutics Inc.) is an FDA approved drug used for reducing pain during sexual intercourse in patients with vaginal atrophy (94573,94576). Other clinical research shows that applying DHEA 10% cream (Diosynth) to the inner thighs daily for 12 months might improve vaginal atrophy by stimulating maturation of the vaginal epithelium in postmenopausal patients. It might also increase bone mineral density in these patients (4242).

POSSIBLY EFFECTIVE

• Aging skin. Oral and topical DHEA have been evaluated for treating aging skin, with promising results. Details: Some clinical research shows that taking DHEA 50 mg daily for 12 months increases epidermal thickness, sebum production, and skin hydration, and decreases facial skin pigmentation in elderly patients (6446). Other preliminary clinical research shows that applying 1% DHEA daily for 4 months improves the appearance of paper-like skin when compared with placebo in postmenopausal patients. It also improves sebum production, skin wrinkling, and skin appearance when compared with baseline (21428).
• Depression. Oral DHEA 30-500 mg daily for up to 8 weeks seems to improve symptoms of depression and dysthymia in patients with depression. Details: Canadian clinical practice guidelines recommend DHEA as a third-line treatment for depression (95691). Most clinical research shows that taking DHEA 30-500 mg daily for around 6-8 weeks improves symptoms of depression and dysthymia when compared with placebo (3270,3864,3892,4233,21404,21405). Additionally, a pooled analysis of these and 9 other clinical studies shows that DHEA can improve depressive symptoms when compared with placebo, although most of the trials evaluated in the analysis included patients without clinically diagnosed depression (104161). Other preliminary clinical research using lower doses of 5-20 mg daily over 3 weeks shows no improvement in depressive symptoms in psychotic patients (21406).
• Infertility. Oral DHEA appears to improve fertility outcomes, including pregnancy and live birth rates, in females undergoing assisted reproduction. However, it is unclear if oral DHEA can reduce the risk for miscarriage after in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI). Details: Meta-analyses of clinical research show that taking DHEA, typically at a dose of 75 mg daily, improves fertility outcomes for females undergoing assisted reproduction (96819,96820,96821,111227). One meta-analysis limited to randomized controlled trials in patients considered poor responders to standard IVF found that taking DHEA prior to IVF or ICSI treatments increases the clinical pregnancy rate by 34% and the rate of live births or ongoing pregnancy by 88% when compared with placebo or no treatment (96820). Another meta-analysis consisting of 16 studies, including both randomized controlled trials and observational research, in patients with diminished ovarian reserve (DOR) or poor ovarian response (POR) undergoing IVF or ICSI shows that taking DHEA 50-90 mg daily is associated with increases in oocyte yields, fertilized oocytes, top-quality embryos, clinical pregnancy rates, and ongoing pregnancy rates when compared with control groups. However, DHEA supplementation was not linked to improvements in live birth rates (111227). In females with various conditions of compromised fertility, some preliminary clinical research shows that taking DHEA 50-75 mg daily for at least 4 months may aid with natural conception, insemination-induced conception, and IVF pregnancy outcomes (21362). Some observational research in older females with DOR has also found that taking DHEA 30 mg three times daily for 12 weeks before IVF cycles is associated with a greater number of retrieved oocytes, improved oocyte quality, and increased cumulative pregnancy rates (103185). Inclusion of lower quality research also supports these findings (21413,21414,88493,96819,96821,99923). However, other research conflicts with findings that show a benefit of DHEA for infertility. (21415,88726,90304,111226). A large clinical study shows that pretreatment with DHEA in infertile females with POR prior to IVF and embryo transfer does not improve the number of retrieved oocytes and the rates of clinical pregnancy, pregnancy loss, and cumulative live births when compared with placebo (111226). Observational research in older patients with DOR suggests that DHEA supplementation is not linked to improved clinical pregnancy or live birth rates when compared with a control group (103185). Other clinical research in females with primary ovarian insufficiency shows that taking DHEA 75 mg daily for 16 weeks might not improve follicle size when compared with placebo (21364). The effect of DHEA pretreatment on miscarriage rates after IVF or ICSI is not clear. A meta-analysis of randomized clinical research does not support the use of DHEA pretreatment for preventing miscarriage (96820). However, when lower quality research is considered, use of DHEA seems to reduce the risk of miscarriage by up to 50% (21418,96819).

POSSIBLY INEFFECTIVE

• Aging. Oral DHEA, taken for up to 2 years, does not appear to improve bone health, quality of life, or sexual function in older adults. Details: Clinical research shows that DHEA, taken as 75 mg daily in males or 50 mg daily in females, for 2 years does not seem to improve body composition, bone mineral density (BMD), insulin sensitivity, or quality of life in people aged 60 years or older who have low DHEA-S levels (15027). Additionally, a pooled analysis of clinical trials shows that taking DHEA 50-1600 mg daily for up to 2 years does not improve body composition, bone health, sexual function, lipid and glycemic parameters, or quality of life in elderly males (88434).
• Muscle strength. Oral DHEA does not seem to improve muscle strength in adults. Details: While some clinical research shows that adults who take DHEA have increased muscle strength when measured by grip strength, leg press, chest press, and other measures, most clinical evidence shows that DHEA provides no benefit to muscle strength in younger and older adults (1365,10406,17617,21392,21419,21420,21421,47198).
• Physical performance. Oral DHEA does not seem to improve physical performance in elderly patients. Details: Most clinical research and a meta-analysis show that older adults who take DHEA do not have increased physical function or performance as measured by oxygen uptake, duration of exercise, balance, and ability to rise from a chair (17617,21420,21421). However, one clinical study shows that taking DHEA 50 mg daily for 6 months improves lower body strength and function by a small amount when compared with placebo in elderly frail females (21392). More research is needed to determine if DHEA is beneficial in specific populations.

LIKELY INEFFECTIVE

• Cognitive function. Oral DHEA does not improve cognitive function or prevent cognitive decline in most populations. Details: In the majority of clinical research, taking DHEA orally does not seem to improve cognitive function or decrease cognitive decline in healthy people over the age of 50 (3893,11334,14862,21333,21445), in peri- or post-menopausal women (6011,21397,21445), in patients with HIV (47435), or in young healthy adults when given as an acute dose (21399). However, preliminary clinical research shows that taking DHEA 50 mg daily for 4 weeks may improve certain measures of visual spatial performance and memory when compared with placebo in middle aged and elderly females (21396,21398).
• Sjogren syndrome. Oral DHEA does not appear to improve symptoms with this condition. Details: Clinical research shows that taking DHEA 50-200 mg daily for 4-12 months does not benefit symptoms of primary Sjogren syndrome when compared with placebo (21354,21358,21363,21365).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Addison disease. It is unclear if oral DHEA is beneficial in patients with this condition. Details: Some preliminary clinical research shows that taking DHEA up to 50 mg daily for up to 12 months improves symptoms of Addison disease, including reversing the loss of bone mineral density (BMD) and lean mass, but without improving cognitive function (8595,21387). However, taking DHEA 50 mg daily for 12 weeks does not appear to improve cognitive or sexual function, body composition, or BMD, although it may improve mood and fatigue (7614,21330,21356).
• Adrenal insufficiency. It is unclear if oral DHEA is beneficial in patients with primary or secondary adrenal insufficiency. Details: Some clinical research shows that taking low-dose DHEA, 20-50 mg daily, improves feelings of well-being, skin and hair, pubic hair growth, and sexuality in females with adrenal insufficiency or androgen deficiency due to hypopituitarism (3231,8593,17218,21317,21370,21385). However, other clinical research shows that taking low-dose DHEA for 3-12 months has little to no effect on quality of life, body composition, physical performance, cardiac function, depression, anxiety, and sexual arousal in patients with primary or secondary adrenal insufficiency (17218,21351,21357,21360,21386,21388,21389). Also, there is contradictory evidence about the effects of DHEA on plasma lipid levels in patients with adrenal insufficiency (21348,21351).
• Athletic performance. It is unclear if oral DHEA can improve sprint performance. Details: Preliminary clinical research in female recreationally trained athletes shows that taking DHEA 100 mg daily for 4 weeks does not improve sprint performance when compared with placebo (99925).
• Cardiovascular disease (CVD). Observational research has found that low DHEA levels are linked to a greater risk for CVD, but it is unclear if supplementation with oral DHEA is beneficial. Details: A meta-analysis of population research shows that patients with CVD and lower blood levels of DHEA-S have a worse overall prognosis when compared with patients with higher levels. Patients with the lowest levels have a 47% increased risk of future mortality events, including a 58% increased risk of fatal cardiovascular events. There was also a 42% increased risk of nonfatal cardiovascular events (96817). In elderly males, population research also shows that low serum levels of DHEA and DHEA-S are associated with an increased risk of coronary heart disease (CHD) but not cerebrovascular disease (90303).
• Cervical dysplasia. It is unclear if intravaginal DHEA is beneficial in patients with cervical dysplasia. Details: Preliminary clinical research shows that DHEA 150 mg intravaginally for up to 6 months reverses dysplasia in 83% of treated females with low-grade cervical dysplasia when compared to baseline (21426). The validity of these findings is limited by the lack of a comparator group.
• Chronic fatigue syndrome (CFS). It is unclear if oral DHEA is beneficial in patients with CFS. Details: Preliminary clinical research shows that oral DHEA 25-100 mg daily for 6 months improves symptoms of CFS by 8.5% to 26% when compared to baseline (7559). The validity of these findings is limited by the lack of a comparator group.
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral DHEA is beneficial in patients with COPD. Details: A small clinical study shows that taking DHEA 200 mg daily for 3 months increases walking distance and improves lung function in patients with COPD when compared to baseline (21395). The validity of these findings is limited by the lack of a comparator group.
• Cocaine dependence. It is unclear if oral DHEA is beneficial for reducing cocaine cravings. Details: A small clinical study shows that taking DHEA 100 mg daily for 12 weeks, in addition to cognitive-behavioral group counseling, does not reduce cocaine craving when compared with counseling alone in cocaine-dependent participants (21411).
• Crohn disease. It is unclear if oral DHEA is beneficial for inducing Crohn disease remission. Details: A small clinical study shows that taking DHEA 200 mg daily for 8 weeks reduces symptoms in some patients with Crohn disease when compared to baseline. Remission occurred in 6 of 7 Crohn patients (21416). The validity of these findings is limited by the small study size and lack of a comparator group.
• Diabetes. Although there has been interest in using oral DHEA for diabetes, there is insufficient reliable information available about the clinical effects of DHEA for this purpose.
• Erectile dysfunction (ED). It is unclear if oral DHEA is beneficial in patients with ED. Details: Preliminary clinical research shows that taking DHEA orally for 24 weeks improves erectile function, orgasmic function, sexual desire, and overall sexual satisfaction in patients with ED. DHEA seems to be beneficial for idiopathic ED or ED secondary to hypertension, but doesn't seem to provide benefit for ED related to diabetes or neurological disorders (793,8596).
• Exercise-induced muscle damage. It is unclear if oral DHEA is beneficial for reducing muscle damage from exercise. Details: Preliminary clinical research shows that taking DHEA 50 mg twice daily for 5 days improves delayed-onset muscle soreness and reduces post-training blood creatinine kinase levels when compared with placebo in young males completing a 5-day exercise training program (88375).
• Fibromyalgia. It is unclear if oral DHEA is beneficial for improving fibromyalgia symptoms. Details: Preliminary clinical research shows that taking DHEA 50 mg daily for 3 months does not reduce fibromyalgia symptoms when compared with placebo in postmenopausal patients with fibromyalgia (21355).
• HIV/AIDS. Small clinical studies suggest that oral DHEA may improve mental health and quality of life in patients with HIV/AIDS, but DHEA does not seem to improve CD4 counts or body composition. Details: Population research shows that levels of DHEA seem to be lower in patients with more severe HIV/AIDS, suggesting that DHEA could be a marker for disease severity. Some evidence suggests that lower DHEA levels are associated with an increased risk of disease progression and AIDS (8598,14278,14279). Some clinical research shows that taking DHEA 50-500 mg daily for 2-4 months might improve mental health and quality of life when compared with placebo (3864,8598,14277,21390). However, taking DHEA in doses up to 2.25 grams daily does not appear to improve CD4 counts, muscle mass, or bone mass when compared with placebo (3865,14277,21390).
• Menopausal symptoms. Oral DHEA might reduce hot flashes and intravaginal DHEA might improve vaginal atrophy and sexual activity; however, oral DHEA does not seem to improve psychological symptoms associated with menopause. Details: Some research shows that taking DHEA 10-25 mg daily for 12 months improves subjective vasomotor symptoms such as hot flashes, as well as psychological symptoms and sexuality (11464,21417). Also, administering a daily ovule containing DHEA (Vaginorm, Recipharm) 3.5-13 mg intravaginally for 12 weeks appears to reverse vaginal atrophy and improve sexual activity in postmenopausal patients with vaginal atrophy (21442). However, other clinical research shows that taking DHEA 50 mg daily for up to 26 weeks does not improve mood, fatigue, cognition, sexual function, or sense of well-being in post- or peri-menopausal patients when compared with placebo (6011,21361). Additionally, a pooled analysis of clinical research shows that DHEA taken orally does not improve psychological symptoms related to menopause (88492).
• Metabolic syndrome. It is unclear if oral DHEA is beneficial for reducing risk for metabolic syndrome. Details: Preliminary clinical research shows that taking DHEA 50 mg daily for 6 months or 100 mg daily for 3 months decreases weight, abdominal fat, and blood pressure and reduces cholesterol, glucose, and insulin levels when compared with placebo in overweight elderly patients (12215,21350).
• Muscular dystrophy. It is unclear if oral DHEA is beneficial in patients with myotonic dystrophy type I. Details: Taking DHEA 100 or 400 mg daily for 12 weeks might not affect muscle strength in patients with myotonic dystrophy type I when compared with placebo (21334). However, intravenous DHEA-S 200 mg daily for 8 weeks appears to improve daily function, muscle strength, and heart function compared with baseline (21434). The validity of this finding is limited by the lack of a control group.
• Obesity. It is unclear if oral DHEA is beneficial for reducing body weight in patients who are obese or overweight. Details: Preliminary clinical research shows that taking DHEA 40 mg sublingually twice daily for 8 weeks, or 1600 mg by mouth for 28 days, does not affect body weight or body composition when compared with placebo in obese adults (21410,21427). Also, preliminary clinical research shows that taking DHEA 50-100 mg daily for 3-12 months does not affect central adiposity in older individuals when compared with placebo (21349).
• Opioid withdrawal. It is unclear if oral DHEA is beneficial in patients with heroin withdrawal. Details: Preliminary clinical research shows that taking DHEA 100 mg daily as adjunct to standard therapy for 12 months does not improve drug withdrawal symptoms in heroin addicts when compared with standard therapy alone (21412).
• Osteoporosis. It is unclear if oral DHEA is beneficial in patients with osteoporosis; any benefit may depend on individual patient characteristics. Details: There is contradictory evidence about the effectiveness of DHEA 50-100 mg daily for improved bone mineral density (BMD) in older adults with osteoporosis or osteopenia (12563,12564,21392), as well as the effectiveness of DHEA for improved BMD in females with anorexia nervosa (12562,21393). One pooled analysis shows that DHEA does not improve BMD in postmenopausal patients (88492), while another shows that DHEA can increase hip BMD in healthy older females, but not males (103186). The reason for these discrepant findings is unclear, but may relate to different patient populations, durations of therapy, and DHEA doses assessed in the included studies. Additionally, most of the studies included in these analyses were of low quality and inadequate statistical power.
• Parkinson disease. Although there has been interest in using oral DHEA for Parkinson disease, there is insufficient reliable information available about the clinical effects of DHEA for this purpose.
• Partial androgen deficiency. It is unclear if oral DHEA is beneficial for symptom improvement in patients with this condition. Details: Preliminary clinical research shows that taking DHEA 25 mg daily for one year might clinically improve mood, fatigue, and joint pain in older males with partial androgen deficiency when compared to baseline (21331). Other preliminary clinical research shows that taking DHEA 50 mg twice daily for 4 months does not improve erectile or sexual function when compared with placebo in hypoandrogenic males (21424).
• Parturition. Intravenous DHEA before the onset of labor may shorten the time to labor onset and shorten labor duration. Details: Clinical research shows that intravenous DHEA-S 100 mg daily for 3 days, or given twice weekly until the onset of labor starting after 38 weeks of gestation, increases cervical ripening and shortens the time to onset of labor and the duration of labor when compared with a control in nulliparous women (21384,21431). Also, intravenous DHEA 50-200 mg given multiple times until the onset of labor starting after 37 weeks of gestation appears to shorten the time to delivery in primiparous and multiparous women (21432,21433). It is unclear if oral DHEA is beneficial for this purpose.
• Rheumatoid arthritis (RA). It is unclear if oral DHEA is beneficial in patients with RA. Details: Preliminary clinical research shows that taking oral DHEA 200 mg for 16 weeks does not reduce symptoms of RA in elderly patients (21422). However, other clinical research in a small number of premenopausal females with RA shows that taking DHEA 50 mg daily for 12 weeks improves quality of life, but not disease activity, when compared with placebo (104159).
• Schizophrenia. It is unclear if oral DHEA is beneficial in patients with schizophrenia. Details: Some research shows that taking DHEA orally improves both negative and positive symptoms in patients with schizophrenia. It may be more effective in females (9692). However, other clinical research shows no benefit (21423).
• Sexual dysfunction. It is unclear if oral or intravaginal DHEA is beneficial for improving sexual dysfunction in males or females. Details: DHEA may be modestly beneficial in some postmenopausal patients with decreased libido or dyspareunia. Preliminary clinical research shows that taking DHEA 50-100 mg daily, or a single dose of DHEA 300 mg, improves sexual desire when compared to baseline (9906,21443). Additional clinical research shows that use of intravaginal DHEA (Vaginorm, Recipharm) at concentrations of 0.25% to 1% daily for 12 weeks might improve sexual function when compared with placebo (47361). However, a pooled analysis shows that DHEA is not associated with improvements in libido or sexual function (88414,88492). DHEA has also been evaluated in other patient populations. Small clinical studies show that taking DHEA doesn't seem to influence response to sexual stimuli in sexually functional premenopausal women (8594) or improve libido in individuals age 40-70 years (21449). Preliminary clinical research in males with hypoactive sexual desire disorder (HSDD) shows that taking DHEA 50 mg twice daily for 6 weeks does not improve erectile or sexual function when compared with placebo (88414). In adults with midlife-onset or HIV-associated depression, preliminary clinical research shows that taking DHEA 90-500 mg daily for 3-8 weeks may improve sexual function and libido when compared with placebo (3864,21405).
• Systemic lupus erythematosus (SLE). Most small clinical studies suggest that oral DHEA may modestly improve symptoms in patients with SLE, but some conflicting research exists. Details: Some clinical research shows that taking DHEA has little to no effect on disease activity in patients with mild to moderate SLE (21425,21447). However, small clinical studies and a meta-analysis of these studies show that taking DHEA in conjunction with conventional treatment may help improve frequency of flare-ups, muscle ache, oral ulcers, and quality of life, reduce corticosteroid doses needed (2113,2114,2136,6068,6447,12561,12574,21346,21447), and improve bone mineral density (6068,6097,6447,21394).
• Ulcerative colitis. It is unclear if oral DHEA is beneficial for inducing ulcerative colitis remission. Details: A small clinical study shows that taking DHEA 200 mg daily for 8 weeks reduces symptoms of ulcerative colitis when compared to baseline in some patients with ulcerative colitis. Remission occurred in 6 of 13 ulcerative colitis patients (21416). The validity of these findings is limited by the small study size and the lack of a comparator group. More evidence is needed to rate DHEA for these uses.

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LIKELY EFFECTIVE

• Pellagra. Oral niacinamide is approved for the treatment of pellagra and niacin deficiency. Details: Niacinamide is FDA-approved for the prevention and treatment of niacin deficiency and pellagra. Niacinamide is sometimes preferred over niacin for this indication because it lacks the vasodilating and flushing effects of niacin (15,6243).

POSSIBLY EFFECTIVE

• Acne. Topical niacinamide seems to improve acne symptoms in some patients. Oral niacinamide has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study shows that applying niacinamide 4% gel twice daily for 8 weeks is as effective as clindamycin 1% gel for reducing the number and severity of acne lesions. The niacinamide gel appears to be more effective in patients with oily skin than those with non-oily skin (93360). Other preliminary clinical research in adults with mild to moderate acne vulgaris shows that applying niacinamide 5% cream twice daily, 10 minutes after applying benzoyl peroxide 2.5% gel, for 12 weeks reduces the number of acne lesions, but not erythema or inflammation, when compared with benzoyl peroxide alone (107711). Niacinamide has also been studied in combination with other ingredients. In preliminary clinical research, oral niacinamide has been reported to improve acne when used in combination with zinc, copper, and folic acid (Nicomide) (25557), or in combination with azelaic acid, zinc, pyridoxine, copper, and folic acid (NicAzel, Elorac Inc.) (90800). In a small observational study, topical niacinamide 4% combined with gallic acid 1% and lauric acid 1% was associated with some improvement in acne (104931). It is unclear if the effects in these studies are due to niacinamide, other ingredients, or the combinations.
• Diabetes. Oral niacinamide does not seem to prevent the onset of type 1 diabetes, although it might slow its progression. Details: Although some older research has suggested that taking high-dose niacinamide can reduce the risk of type 1 diabetes in high-risk children (4874), results from higher quality, more rigorous clinical trials show that taking niacinamide up to 3 grams daily for 5 years does not prevent the onset of type 1 diabetes in first-degree relatives of patients with type 1 diabetes (4875,25553,25554). However, taking niacinamide 1.2 grams/m2 daily for 5 years may prevent the loss of beta-cell function in these patients (25555). Also, there is evidence showing that niacinamide can preserve residual beta-cell function in patients with newly diagnosed type 1 diabetes (4877,4878,4879,4880,25556). Clinical trials, including one placebo-controlled trial and one vitamin E-comparison study, show niacinamide can prolong the "honeymoon period" in those newly diagnosed with type 1 diabetes, when the pancreas is still capable of producing some insulin (4877,4878,4879,4880,25556). However, some scientists have raised concerns about potential induction of insulin resistance with short-term use of niacinamide 2 grams daily for 2 weeks (4881). Niacinamide has also been evaluated in adults with type 2 diabetes. A small clinical study in lean patients with type 2 diabetes who failed sulfonylurea therapy shows that taking niacinamide 500 mg three times daily for 6 months in addition to continuing insulin or a sulfonylurea increases C-peptide release and improves insulin secretion when compared with insulin alone (4882).
• Hyperphosphatemia. Adding oral niacinamide to standard treatment with phosphate binders further lowers blood levels of phosphorus in patients on hemodialysis. Details: A meta-analysis of nine small clinical trials in patients on hemodialysis with hyperphosphatemia who are using a phosphate binder shows that taking niacinamide 250-1500 mg daily for 2-6 months lowers serum phosphorus and parathyroid hormone levels when compared with placebo (98940) Another meta-analysis of two small clinical trials in the same patient population also shows that taking niacinamide, titrated from 500 mg to 1500 mg daily over 8 weeks, reduces serum phosphorus levels by about 0.9 mg/dL when compared with placebo (94188). Other clinical research in this population shows that taking modified-release niacinamide 250-1500 mg orally daily for 12-24 weeks also lowers serum phosphate and parathyroid levels when compared with placebo. However, these effects were not maintained at 40-52 weeks follow-up (107709,110499). In addition, this product was not compared with immediate-release niacinamide. Niacinamide has also been studied in place of phosphate binders. One small clinical study in patients on hemodialysis with hyperphosphatemia shows that taking niacinamide 500-1750 mg daily for 12 weeks, beginning 2 weeks after discontinuation of phosphate binders, decreases serum phosphorus levels by 1.5 mg/dL and intact parathyroid hormone levels by 50 pg/mL, without affecting calcium levels, when compared to baseline (25561).The validity of these findings is limited due to the lack of a control group.
• Nonmelanoma skin cancer. Oral niacinamide might reduce the rate of nonmelanoma skin cancer development. Details: One clinical study in patients with a history of nonmelanoma skin cancers shows that taking niacinamide 500 mg orally twice daily for 12 months reduces the rate of new nonmelanoma skin cancers at 12 months by 23% and the number of actinic keratoses by 13% when compared with placebo (93362). Other clinical research shows that taking niacinamide (Nature's Own, Virginia) 500 mg orally once or twice daily for 4 months reduces the total number of actinic keratoses by up to 35% and decreases the odds of developing at least one nonmelanoma skin cancer by 86% when compared with placebo in patients with at least four actinic keratoses (93365). However, some conflicting research exists. One small clinical study in adults with actinic keratoses shows that taking niacinamide 500 mg twice daily for 120 days does not reduce the number of actinic keratoses when compared with control. However, the validity of this study is limited by the short study duration (107714). A meta-analysis of many small clinical trials shows that using niacinamide, up to 2000 mg orally or 4% topically, daily for 1 month to 5 years lowers the risk of skin cancer, including basal cell carcinoma and cutaneous squamous cell carcinoma by 50% when compared with control. Using niacinamide did not reduce the risk of actinic keratoses. However, the validity of this study is limited by inclusion of populations with different cancer risks and high heterogeneity (110497).
• Osteoarthritis. Oral high-dose niacinamide might be beneficial for improving osteoarthritis symptoms. Details: Clinical research in patients with osteoarthritis shows that taking niacinamide 3 grams daily in six divided doses for 12 weeks improves joint flexibility, reduces inflammation, and modestly decreases use of nonsteroidal anti-inflammatory drugs (NSAIDs) when compared with placebo (4883).

POSSIBLY INEFFECTIVE

• Brain tumor. Adding high-dose oral niacinamide to chemotherapy does not seem to improve survival in patients with brain tumors. Details: Preliminary clinical research in patients with surgically resected brain tumors shows that treatment with radiotherapy, niacinamide, and carbogen does not improve survival when compared with radiotherapy alone or radiotherapy plus carbogen (11695,11696).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Although there is interest in using oral niacinamide for age-related cognitive decline, there is insufficient reliable information about the clinical effects of niacinamide for this purpose.
• Age-related macular degeneration (AMD). Oral niacinamide has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with early-stage age-related maculopathy shows that taking a combination of niacinamide 18 mg, vitamin E 20 mg, and lutein 15 mg daily for nearly a year improves retinal function when compared with no treatment (60134). It is unclear if this effect is due to niacinamide, other ingredients, or the combination.
• Aging skin. It is unclear if topical niacinamide improves symptoms of aging skin. Details: A small study in females with signs of facial photo-aging shows that applying niacinamide 5% cream to half of the face twice daily for 12 weeks improves blotchiness, the appearance of wrinkles, skin elasticity, and skin pigmentation when compared with applying placebo cream to the other half of the face (25551).
• Atopic dermatitis (eczema). It is unclear if topical niacinamide improves eczema symptoms. Details: A small clinical study in patients with atopic dermatitis and dry skin shows that applying niacinamide 2% cream twice daily for 8 weeks decreases skin water loss and improves skin hydration when compared with using a white petrolatum moisturizer (25560).
• Attention deficit-hyperactivity disorder (ADHD). Oral niacinamide has only been evaluated in combination with other vitamins; its effect when used alone is unclear. Details: A small clinical study in children with ADHD shows that taking a maximum of niacinamide 3 grams, ascorbic acid 3 grams, calcium pantothenate 1.2 grams, and pyridoxine 600 mg daily for 3 months seems to improve behavior in 29% of participants when compared with baseline (9957). The validity of this finding is limited by the lack of a comparator group.
• Bladder cancer. Oral niacinamide has only been evaluated in combination with carbogen for improving survival in advanced bladder cancer; its effect when used alone is unclear. Details: A phase II clinical study in patients with locally advanced bladder cancer shows that adding inhaled carbogen and oral niacinamide 40-60 mg/kg about 2 hours before radiotherapy shows a trend to improved survival at 3 years when compared with inhaled carbogen and radiotherapy (25558), and a larger phase III study shows that carbogen and oral niacinamide improves 3-year survival by about 13% when compared with radiotherapy alone (93366). An observational follow-up of the phase III study found a trend to increased survival at 5 years in the carbogen and niacinamide group when compared with radiotherapy alone. And in a subgroup of patients with tumor necrosis, the 5-year survival was significantly greater with carbogen and niacinamide when compared with radiotherapy alone (93356). It is unclear if these effects are due to niacinamide, carbogen, or the combination.
• Child growth. It is unclear if oral niacinamide improves child growth. Details: Preliminary clinical research in children in rural Tanzania shows that supplementing niacinamide orally from birth to 18 months of age does not improve length-for-age, weight-for-age, or head circumference when compared with control. Niacinamide was initially supplemented to breast-feeding mothers, 250 mg daily, until 6 months of age, followed by 100 mg daily taken by the child until 18 months of age (107713).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral niacinamide is beneficial for COVID-19. Details: Observational research in adults with acute kidney injury secondary to coronavirus disease-19 infection has found that taking niacinamide 1000 mg orally daily for 7 days is associated with a 55% lower risk of mortality when compared with control. However, taking niacinamide was not associated with a lower risk of renal replacement therapy (110500).
• Cutaneous lupus erythematosus (CLE). It is unclear if topical niacinamide is beneficial for CLE. Details: Preliminary clinical research in adults with discoid lupus erythematosus, a type of CLE, shows that applying topical niacinamide 2% to 4% twice daily for 12 weeks modestly improves lesion scores, but not quality of life scores, when compared with placebo. However, the study may have been inadequately powered to detect a difference between groups (110498).
• Depression. Although there is interest in using oral niacinamide for depression, there is insufficient reliable information about the clinical effects of niacinamide for this condition.
• Diabetic neuropathy. Oral niacinamide has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with diabetic polyneuropathy shows that taking a specific combination product (Cytoflavin, Polysan) containing niacinamide, inosine, riboflavin, and succinate daily for 12 weeks improves symptom scores, including paresthesia and numbness scores, when compared with placebo. The therapy was administered intravenously, containing niacinamide 20 mg, inosine 40 mg, riboflavin 4 mg, and succinate 200 mg, for 10 days followed by orally, containing niacinamide 50 mg, inosine 100 mg, riboflavin 10 mg and succinate 600 mg, for the remainder of the study (110503).
• Erythema. Topical niacinamide has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: There is interest in using niacinamide to reduce the side effects of topical tretinoin, including erythema. A small preliminary clinical study in patients using isotretinoin for acne shows that applying a specific cream (Sebiaclear Hydra, SVr Laboratoire Dermatologique) containing niacinamide 5% and omega-ceramides 8% twice daily for 6 months reduces isotretinoin-induced erythema, dryness, and itching of the skin when compared with a glycerin placebo (98938). It is not clear if this effect is due to niacinamide, omega-ceramides, or the combination.
• Head and neck cancer. Oral niacinamide has only been evaluated in combination with carbogen for improving survival in laryngeal cancer; its effect when used alone is unclear. Details: A phase III clinical trial in patients with laryngeal cancer shows that treatment with accelerated radiotherapy plus carbogen and niacinamide 60 mg/kg taken orally 1-1.5 hours prior to each fraction of radiation improves local tumor control, but does not improve overall survival or 5-year disease-free survival, when compared with accelerated radiotherapy alone. In a subgroup of patients with hypoxic tumors, anemia, or high expression of epidermal growth factor receptor, receiving niacinamide and carbogen seems to improve both survival and tumor control when compared with radiotherapy alone (93358,93359,93363).
• Melasma. It is unclear if topical niacinamide improves uneven skin pigmentation. Details: A small clinical study in Japanese females with uneven facial hyperpigmentation shows that applying niacinamide 5% moisturizer to the face twice daily reduces hyperpigmentation and increases skin lightness after 4 weeks when compared with placebo moisturizer. However, further improvements are not observed after another 4 weeks of treatment (25552). Another small clinical study in Korean females with uneven facial hyperpigmentation shows that applying a moisturizer containing niacinamide 2% plus tranexamic acid 2% (Regederm RX White Project, Aestura) twice daily for 8 weeks reduces skin pigmentation by about 9% when compared with a placebo cream (93361).
• Non-Hodgkin lymphoma. It is unclear if adding oral niacinamide to chemotherapy reduces relapses of refractory lymphoma. Details: One small clinical study in patients with relapsed or refractory lymphoma shows that 24% of patients achieve complete or partial remission and 57% achieve disease stabilization when compared with baseline, following treatment with vorinostat 400 mg daily and niacinamide titrated from 20 mg/kg to 100 mg/kg over the first 14 days of a 21-day cycle for up to 18 cycles (93355). It is unclear how these outcomes compare to using vorinostat alone, or to other control treatments.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral niacinamide is beneficial for NAFLD. Details: Preliminary clinical research in adults with NAFLD and diabetes shows that taking a specific niacinamide product (Nature's Life) 1000 mg orally daily for 12 weeks does not improve liver function tests, liver steatosis, or liver fibrosis when compared with no intervention. However, some quality of life domain scores were moderately improved. However, the study may have been inadequately powered to detect a difference between groups (110502).
• Premenstrual syndrome (PMS). Although there is interest in using oral niacinamide for PMS, there is insufficient reliable information about the clinical effects of niacinamide for this condition.
• Pruritus. It is unclear if oral niacinamide reduces pruritus in patients with kidney failure. Details: A small clinical study in patients with pruritus due to kidney failure shows that taking niacinamide sodium 500 mg twice daily for 4 weeks does not reduce pruritus severity when compared with placebo (93364). This study is limited due to small size and short study duration.
• Psoriasis. It is unclear if oral niacinamide is beneficial for psoriasis. Details: Preliminary clinical research in adults with mild to moderate psoriasis shows that applying niacinamide 4% cream topically twice daily for 12 weeks improves psoriasis scores by 31% when compared with baseline. The validity of these results is limited by the lack of a comparator group (110501).
• Rosacea. Oral niacinamide has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that 71% of adult and adolescent patients with rosacea who take a combination product (Nicomide) containing niacinamide 750 mg, zinc 25 mg, copper 1.5 mg, and folic acid 500 mcg once or twice daily report improvement in appearance after 4 weeks when compared to baseline (25557). The validity of these findings is limited by the lack of a control group.
• Schizophrenia. Although there is interest in using oral niacinamide for schizophrenia, there is insufficient reliable information about the clinical effects of niacinamide for this condition.
• Seborrheic dermatitis. It is unclear if topical niacinamide is beneficial for reducing seborrheic dermatitis symptoms. Details: One small clinical study in patients with seborrheic dermatitis shows that applying niacinamide 4% cream once daily for 12 weeks reduces the severity of symptoms such as redness and scaling by 75%, compared with a 35% reduction when using a placebo cream (93357). More evidence is needed to rate niacinamide 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.

(Read more about PREGNENOLONE)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Most studies have been small and lasted from a few weeks to 6 months, with usual doses of 50 mg daily (793,1635,2133,3231,4249,4251,4252,4253,4254,4255,9691)(9692,10986,12215,12564,14277,21416,88726,90304,99925). Some studies have also used oral DHEA with apparent safety for 12-24 months (2113,6446,10406,11464,12561,15027,88492). ...when used intravaginally and appropriately. Intravaginal ovules of DHEA 3.25 mg to 13 mg have been safely used for up to 12 weeks (21320,21429,21430). ...when used topically and appropriately. A DHEA cream 1% to 10% has been safely used for up to 12 months (4242,21428).

POSSIBLY UNSAFE ...when used orally in high doses or long-term. There is concern that long-term use or use of amounts that cause higher than normal physiological DHEA levels might increase the risk of prostate cancer (2111,12565), breast cancer (10370,10401,10403), or other hormone-sensitive cancers (6445). In some cases, 50-100 mg daily can produce slightly higher than normal physiological DHEA levels (4249,4251). There is insufficient reliable information available about the safety of using DHEA intravenously or intramuscularly.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally. DHEA can cause higher than normal androgen levels (2133,4249,4251,4253), which might adversely affect pregnancy or a nursing infant.

(Read more about DHEA)

LIKELY SAFE ...when prescription products are used orally and appropriately (12033). ...when niacinamide supplements are taken orally in doses below the tolerable upper intake level (UL) set by the Institute of Medicine (IOM). The UL of niacinamide is 30 mg daily for adults 18 years of age and 35 mg daily for adults 19 years and older (6243).

POSSIBLY SAFE ...when used orally in doses greater than 30 mg but less than 900 mg daily. The European Food Safety Authority has set the tolerable upper intake level (UL) of niacinamide at 900 mg daily (104937). However, oral niacinamide has been safely used in doses up to 1500 mg daily for 12 weeks in some clinical trials (25561,94188,98940,107709,110502). ...when used topically and appropriately for up to 12 weeks (5940,93360,110498,110501).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Niacinamide has been safely used in children for up to 7 years in doses below the tolerable upper intake level (UL) (4874,9957). The UL of niacinamide for children by age is: 1-3 years, 10 mg daily; 4-8 years, 15 mg daily; 9-13 years, 20 mg daily; 14-18 years, 30 mg daily (6243).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the tolerable upper intake level (UL) for niacinamide. The UL of niacinamide during pregnancy and lactation is 30 mg daily for those 14-18 years of age and 35 mg daily for those 19 years and older (6243). There is insufficient reliable information available about the safety of larger oral doses of niacinamide or topical niacinamide; avoid using.

(Read more about NIACINAMIDE)

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.

(Read more about PREGNENOLONE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Human and laboratory research show that DHEA and DHEA-S can inhibit platelet aggregation (19109,19127).

ANTIDEPRESSANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might increase the risk of psychiatric adverse events when used with antidepressants.  Details In a human case report, the use of a selective serotonin reuptake inhibitor (SSRI) with DHEA caused a manic episode (7023). Concern for this interaction may be greater in younger individuals with higher baseline DHEA levels.

AROMATASE INHIBITORS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might interfere with the clinical effects of aromatase inhibitors.  Details DHEA is a potent estrogen agonist, which may antagonize the anti-estrogen activity of aromatase inhibitors (10401).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might increase the levels of drugs metabolized by CYP3A4.  Details Some preliminary evidence shows that DHEA may inhibit CYP3A4 (1389); however, the clinical significance of this potential interaction is not known.

ESTROGENS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might increase the effects and adverse effects of estrogen therapy.  Details DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones (6012,7614,8593,10986,12651,12564,15027,21321,21323,21324)(21325,21326,21327,21328,21330,21331,21356,21364,21389,21393)(21397,21398,21417,21419,21427,47273,47348,88375,90304). Also, in clinical research, estrogen-progestin oral contraceptives and conjugated estrogens reduce blood levels of DHEA and DHEA-S (21372,21373,21374,21437,21438). The clinical significance of these findings is unclear.

FULVESTRANT (Faslodex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might interfere with the anti-estrogen effects of fulvestrant.  Details DHEA is a potent estrogen agonist (10401). Some research shows that it can overcome the estrogen receptor antagonist action of fulvestrant in estrogen-receptor positive cancer cells (10370).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might interfere with the anti-estrogen effects of tamoxifen.  Details DHEA is a potent estrogen agonist. Some research shows that it can overcome the estrogen receptor antagonist activity of tamoxifen in estrogen-receptor positive cancer cells (10370,10403).

TESTOSTERONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, DHEA might increase the effects and side effects of testosterone therapy.  Details DHEA is a precursor to estrogen and androgen and is metabolized into those substances. In clinical research, DHEA supplements increase the levels of these hormones (6012,7614,8593,10986,12651,12564,15027,21321,21323,21324)(21325,21326,21327,21328,21330,21331,21356,21364,21389,21393)(21397,21398,21417,21419,21427,47273,47348,88375,90304,99924,99925,104162). The clinical significance of these findings is unclear.

TRIAZOLAM (Halcion) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D DHEA can increase blood levels of triazolam.  Details Administration of DHEA 200 mg daily for two weeks was shown to inhibit the cytochrome P450 3A4 (CYP3A4) metabolism of triazolam. This inhibition appears to be due to DHEA-S, rather than DHEA (1389).

TUBERCULOSIS VACCINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D DHEA might reduce the effectiveness of the tuberculosis vaccine.  Details Animal research shows that high doses of DHEA can reduce the efficacy of the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine (21316).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, niacinamide may have additive effects when used with anticoagulant or antiplatelet drugs, especially in patients on hemodialysis.  Details Several cases of thrombocytopenia have been reported for hemodialysis patients treated with niacinamide 1 gram daily. Hemodialysis patients receiving niacinamide had almost a three-fold higher risk of developing thrombocytopenia when compared with those receiving placebo (25563,98940).

CARBAMAZEPINE (Tegretol) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Niacinamide might increase the levels and adverse effects of carbamazepine.  Details Plasma levels of carbamazepine were increased in two children given high-dose niacinamide, 60-80 mg/kg/day. This might be due to inhibition of the cytochrome P450 enzymes involved in carbamazepine metabolism (14506). There is not enough data to determine the clinical significance of this interaction.

PRIMIDONE (Mysoline) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Niacinamide might increase the levels and adverse effects of primidone.  Details Case reports in children suggest niacinamide 60-100 mg/kg/day reduces hepatic metabolism of primidone to phenobarbital, and reduces the overall clearance rate of primidone (14506); however, there is not enough data to determine the clinical significance of this potential interaction.

(Read more about NIACINAMIDE)

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).

(Read more about PREGNENOLONE)

General ...Orally and topically, DHEA seems to be well tolerated when used in typical doses, short-term. However, there is some concern that long-term oral use of DHEA may be linked to a greater risk for cancer.
Most Common Adverse Effects:
Orally: Acne, headache, insomnia, mood changes, and nausea. In females, masculinization symptoms including deepening of the voice, increased size of genitals, irregular menses, oily skin, reduced breast size, and unnatural hair growth. In males, aggression, breast tenderness or enlargement (gynecomastia), urinary urgency, and testicular wasting.
Serious Adverse Effects (Rare):
Orally: Possible increased risk for cardiovascular events and various types of cancer.

Cardiovascular ...Incidences of arrhythmia (21334,47540), chest pain (21332,21333), palpitations (21332,21333,88492), hypertension, and transient ischemic attacks (21353,21354,47300) have been reported. DHEA has also been found to decrease high-density lipoprotein (HDL) levels (21344,21345,21346,21347,21348,21349) and increase triglycerides (21334).

Dermatologic ...Acne has been the most commonly reported adverse effect in human research, particularly in females (2113,2114,4242,7614,7559,12561,12574,21346,21351,21354)(21355,21356,21357,21358,21360,21361,21362,21363,21364,47300)(47355,47409,90304,103185). However, it is generally mild and may be treated by reducing the dose (7559). Incidences of contact dermatitis (47402), acneiform dermatitis (2113), greasy hair and skin (17218,21351,21355,21363,21387,21389,47355), keratosis (47402), skin rash (12574,21361,21363), erythema (21334), scalp itching (17218,21357), and skin spots (21387) have also been reported. Increased hair growth and hirsutism have been noted in several clinical trials, including the development of mild mustache in females (2114,4242,12561,12574,17218,21346,21351,21354,21355,21358) (21361,21362,21363,21370,21387,21389,21415,47300). Increased perspiration and odor have also been reported in human research (17218,21354,21356,21357).

Endocrine ...In postmenopausal patients, high doses of DHEA (1600 mg daily) induced insulin resistance, reportedly due to increased androgen levels that occurred during supplementation (21324).

Gastrointestinal ...Gastrointestinal disturbances such as nausea, diarrhea, and abdominal discomfort have been noted in human research (2111,6098,7559,12574,21348,21358,21386).

Genitourinary ...In older adults, elevated and severe urinary symptoms (as evidenced by scores of more than 20, using the American Urological Association Symptom Index for Benign Prostatic Hyperplasia [International Prostate Symptom Score]) and urinary tract infection were reported (21353). Rare incidences of abnormal menses (2114) and increased discharge (21415) have been reported. DHEA has been associated with hematuria (47300).

Hepatic ...Elevated liver enzymes have been reported following DHEA supplementation (21364,47300). However, an analysis of multiple studies in varied patient populations taking DHEA supplements found no elevations in liver enzymes (107791).

Musculoskeletal ...Incidences of asthenia, arthralgia, and myalgia, including calf cramps, have been reported (12574,21354,21358,21365,47355).

Neurologic/CNS ...In humans, dizziness, fatigue, malaise, sleep disturbances, increased dreaming, night sweats, restlessness, "painful spots," and a crawling scalp sensation have been reported (3865,21354,21363,21389). There is a case of seizure associated with DHEA use in a 30 year-old female with fragile X syndrome and no history of convulsive disorder who used DHEA to try to improve ovarian production (47344).

Ocular/Otic ...In patients with Sjögren syndrome, maculae lesions, ocular pain and dryness, and painful eye exams have been reported (21358,21363,21365).

Oncologic ...Preclinical research suggests that DHEA may increase the risk of cancer, particularly prostate, liver, breast, and pancreatic cancers (2111,10370,10401,10403,12565,21332,21333,21334,47251,47256)(47366,47388,47539). High concentrations of DHEA in postmenopausal patients have been associated with an increased risk of breast cancer (2115,6445).

Psychiatric ...DHEA-induced mania has been reported (5870,6102,7023,21383). Clinical studies have also reported anxiety, nervousness, irritability, emotional change, and depression in patients receiving DHEA (2114,21358,21360,21370).

Pulmonary/Respiratory ...Increased cough and nasal congestion have been noted in human research (3865,11334). A report of acute respiratory failure was made in clinical study evaluating the use of DHEA in patients with myotonic dystrophy (type 1) (21334).

Other ...Perceived increases in weight gain have been reported with use of DHEA (2114,21361).

(Read more about DHEA)

General ...Orally, niacinamide is well tolerated in amounts typically found in food. When used topically and orally in higher doses, niacinamide seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Dizziness, drowsiness, itching, gastrointestinal disturbances, headache, and rash.
Topically: Burning sensation, itching, and mild dermatitis.

Dermatologic ...Orally, large doses of niacinamide are associated with occasional reports of rashes, itching, and acanthosis nigricans (4880,11695,11697,14504,107709). Topically, application of niacinamide in a cream has been reported to cause a burning sensation, itching and pruritus, crusting, and mild dermatitis (93357,93360,110501,110498).

Endocrine ...Orally, niacinamide in high doses, 50 mg/kg daily, has been associated with modestly higher insulin requirements in patients with type 1 diabetes, when compared with taking niacinamide 25 mg/kg daily. Theoretically, high-dose niacinamide might increase insulin resistance, although to a lesser extent than niacin (4881,14512).

Gastrointestinal ...Orally, large doses of niacinamide can cause gastrointestinal disturbances including nausea, vomiting, heartburn, anorexia, epigastric pain, flatulence, and diarrhea (6243,11694,11695,11696,11697,107709).

Hematologic ...Orally, niacinamide supplementation might increase the risk for thrombocytopenia in patients undergoing hemodialysis (98940,107709). A meta-analysis of small clinical studies shows that taking niacinamide during hemodialysis to reduce phosphate levels is associated with a 2.8-fold increased risk for thrombocytopenia when compared with placebo. In one of the included studies, platelet levels returned to normal within 20 days after niacinamide discontinuation (98940).

Hepatic ...Orally, older reports of elevated liver function tests with high doses of niacinamide (3 grams or more daily) have raised concerns about liver toxicity. However, newer studies have not reported this concern; it is possible that some of these cases were due to contamination with niacin (4880,11694,11695,14503).

Neurologic/CNS ...Orally, large doses of niacinamide can cause dizziness, drowsiness, and headaches (11694,11695,11696,11697,107709).

(Read more about NIACINAMIDE)

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).

(Read more about PREGNENOLONE)