Deer Antler Velvet Spray 1234 [Discontinued] by Creative Bioscience

Alpha hydroxy acids represent a group of natural chemicals that are used alone or in combination. See specific monographs for effectiveness information.

(Read more about ALPHA HYDROXY ACIDS (AHAs))

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral deer velvet for anti-aging effects, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Anemia of chronic disease. Although there has been interest in using oral deer velvet for anemia of chronic disease, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Asthma. Although there has been interest in using oral deer velvet for asthma, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Athletic performance. It is unclear if oral deer velvet extract or powder is effective for improving athletic performance. Details: One small clinical study in active adult males participating in a strength training program shows that taking deer velvet extract 300 mg or deer velvet powder 1.5 grams daily for 10 weeks does not improve squat strength or aerobic capacity when compared with placebo. However, taking deer velvet might produce modest improvements in knee extension strength and endurance (47108).
• Cardiovascular disease (CVD). Although there has been interest in using oral deer velvet for CVD, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Cognitive function. Although there has been interest in using oral deer velvet to improve cognitive function, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Erectile dysfunction (ED). Although there has been interest in using oral deer velvet for ED, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Fatigue. Although there has been interest in using oral deer velvet for fatigue, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Hypertension. Although there has been interest in using oral deer velvet for hypertension, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Osteoporosis. Although there has been interest in using oral deer velvet for osteoporosis, there is insufficient reliable information about the clinical effects of deer velvet for this purpose.
• Sexual desire. It is unclear if oral deer velvet powder is effective for improving sexual desire. Details: One small clinical study in adult males shows that taking deer velvet powder 1 gram daily for 12 weeks does not improve sexual function or desire in males or their female partners when compared with placebo (47106).
• Uterine fibroids. Deer velvet has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of nine small clinical trials shows that taking traditional Chinese medicine decoctions containing deer velvet or ejiao, a gelatin product extracted from donkey skin, along with other herbal ingredients plus mifepristone reduces uterine fibroid volume and improves symptoms associated with uterine fibroids when compared with mifepristone alone (106850). It is unclear if these findings are due to deer velvet, other ingredients, or the combination.
• Wound healing. Although there has been interest in using oral deer velvet for wound healing, there is insufficient reliable information about the clinical effects of deer velvet for this purpose. More evidence is needed to rate deer velvet for these uses.

(Read more about DEER VELVET)

LIKELY EFFECTIVE

• Dyslipidemia. Niacin prescription products, in doses of 500 mg or greater, are FDA-approved for primary hyperlipidemia and mixed dyslipidemia. Niacin dietary supplements are generally available in lower doses and have not been shown to improve lipid levels. Details: Prescription niacin is not routinely recommended as second-line therapy for patients who primarily need to decrease low-density lipoprotein (LDL) cholesterol. This is due to results from clinical trials showing no effect on cardiovascular related events or mortality (93346,93354,96208,96211,97308,97477,97336). However, niacin might be considered for patients with mixed hyperlipidemia or patients who need to increase high-density lipoprotein (HDL) cholesterol and lower triglycerides. Niacin might also be effective for isolated hypoalphalipoproteinemia (4817). The most pronounced increases in HDL and decreases in triglycerides occur at 1-1.5 grams daily, and the greatest LDL reduction occurs at 2-3 grams daily. Niacin reduces LDL cholesterol by up to 25%, compared with up to a 55% reduction with statins. High-dose niacin can also decrease triglycerides by 20% to 50%, increase HDL by 13% to 35%, decrease apolipoprotein B levels by 2% to 20%, and decrease lipoprotein(a) levels by 23% (4818,4886,4887,4888,4889,4890,12033,25567,93347,96213). The effects of higher dose extended-release niacin on LDL cholesterol and triglycerides appear to be greater in females than males (25565). Experts recommend maximizing statins first because they have the best evidence for improving cardiovascular outcomes (97477,97336,97337). However, if patients cannot reach their LDL goal with a statin alone or if they cannot tolerate a statin, niacin might be combined with other cholesterol-lowering drugs when diet and single-drug therapy are not adequately effective (8545,25566,93351,94191,97337). Adding low-dose niacin, 50 mg daily, to statin therapy has no additional benefit on lipid levels (8546). Population research in adults without dyslipidemia has also found that higher dietary intake of niacin for 3-10 years is associated with a 29% lower risk of developing dyslipidemia when compared with low dietary niacin intake (110493).
• Pellagra. Oral niacin is FDA-approved for the prevention and treatment of pellagra. Details: Population research has found that low consumption of niacin is associated with an increased risk of developing pellagra (25903). Taking niacin 500-1000 mg daily can resolve symptoms of pellagra within a week of treatment initiation (25904). However, niacinamide is sometimes preferred for this indication because it lacks the vasodilating effects of niacin (15,6243).

POSSIBLY EFFECTIVE

• HIV/AIDS-related dyslipidemia. Oral niacin seems to improve lipid levels in patients with dyslipidemia due to HIV/AIDs. Details: Small clinical trials in HIV patients with dyslipidemia associated with antiretroviral therapy shows that taking extended-release niacin (Niaspan, Abbott Laboratories) titrated up to 2 grams daily for 14-48 weeks improves total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels when compared to baseline (25570,25902). Other preliminary clinical research in this population shows that taking extended-release niacin (Niaspan, Abbott Laboratories) titrated to 2 grams daily for up to 2 years improves HDL cholesterol levels, but not total cholesterol or triglyceride levels, when compared with no treatment (25569).
• Metabolic syndrome. Oral niacin seems to improve lipid levels in patients with metabolic syndrome. Details: Clinical research shows that taking niacin (Niaspan, Abbott Laboratories) 2 grams daily orally for 16 weeks reduces triglyceride levels by 39 mg/dL and increases high-density lipoprotein (HDL) cholesterol by 5 mg/dL when compared to baseline in patients with metabolic syndrome. These improvements are significant when compared with placebo and are further increased when niacin is taken along with prescription omega-3 ethyl esters (Lovaza, GlaxoSmithKline Pharmaceuticals) 4 grams daily orally (93353). However, niacin does not seem to improve postprandial glucose levels in patients with metabolic syndrome (97333).

INEFFECTIVE

• Cardiovascular disease (CVD). Oral niacin does not seem to reduce cardiovascular-related events in patients with or without CVD. Details: Overall, niacin is not recommended for primary or secondary prevention of CVD. Most clinical trials and meta-analyses conducted prior to 2011 showed a reduction in cardiovascular-related events, cardiovascular-related mortality, and all-cause mortality in patients taking niacin alone or in combination with a statin or clofibrate for primary or secondary prevention of CVD (4847,7388,25095,25911,25912,93349). However, recent meta-analyses of these studies and additional moderate-to-high quality research conducted in over 39,000 patients show no effect of niacin on cardiovascular-related events, cardiovascular-related mortality, or overall mortality (93346,93354,96208,96211,97308). Additionally, one meta-analysis shows that patients taking niacin are twice as likely to report side effects when compared with placebo (96211).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if oral niacin is beneficial for reducing Alzheimer disease risk. Details: Observational research has found that consuming higher amounts of niacin (17-45 mg daily) from food and supplements is associated with a slower cognitive decline and a lower risk of developing Alzheimer disease when compared with people who consume less niacin (14 mg daily) (12077). It is not known if the risk of Alzheimer disease is reduced by taking a stand-alone niacin supplement.
• Atherosclerosis. It is unclear if oral niacin prevents atherosclerosis progression. Details: Preliminary clinical studies show that taking niacin orally, in combination with colestipol for up to 2 years, might modestly reduce progression of atherosclerosis as measured by coronary lesions and carotid arterial intima-media thickness in high-risk males with existing coronary atherosclerosis (25906,25909,25910). However, niacin does not seem to be better than statins. One clinical study in adults with atherosclerosis and peripheral arterial disease shows that taking extended-release niacin 1500 mg, simvastatin 40 mg, and ezetimibe 10 mg daily for 2 years does not reduce atherosclerosis of the superficial femoral artery when compared with simvastatin alone (96208). Niacin has also not been shown to prevent cardiovascular events or mortality (93346,93354,96208,96211,97308).
• Athletic performance. It is unclear if oral niacin improves athletic performance. Details: Preliminary clinical research in untrained adult males shows that taking niacin 1000 mg orally once before a cycling test does not improve power, respiratory exchange ratio, or time to exhaustion when compared with placebo. In addition, these measures were significantly worse when compared with taking caffeine 5 mg/kg orally as a single dose (107942). Clinical research in untrained males also shows that taking a supplement containing niacin 40 mg, caffeine 400 mg, capsicum extract 66.7 mg, and black pepper extract 10 mg prior to exercising does not improve strength, time to exhaustion, or maximal oxygen consumption when compared with placebo (37873).
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral niacin for ADHD, there is insufficient reliable information about the clinical effects of niacin for this condition.
• Cancer. It is unclear if dietary niacin is beneficial for cancer. Details: Population research in adults with cancer has found that high dietary niacin intake is associated with 49% and 27% lower risk of cancer-related mortality and all-cause mortality when compared with low dietary niacin intake. The same study also found that taking niacin supplements is associated with a lower risk of cancer-related mortality, but not all-cause mortality when compared with not taking niacin supplements (110496).
• Cataracts. It is unclear if oral niacin is beneficial for preventing cataracts. Details: Population research has found that high dietary intake of niacin is associated with a reduced risk of nuclear cataracts (6378). However, there is no reliable evidence that niacin supplements reduce the risk of cataracts.
• Cholera. It is unclear if oral niacin is beneficial for cholera. Details: One small clinical study in adults with severe cholera shows that taking 1-2 grams niacin orally reduces fluid loss in the stool by 31% to 47% in the first 16 hours when compared with control. The 2 gram dose seemed to result in a greater reduction in fluid loss than the 1 gram dose (4868).
• Erectile dysfunction (ED). It is unclear if oral niacin is beneficial in patients with ED and dyslipidemia. Details: Clinical research in patients with erectile dysfunction and dyslipidemia shows that taking extended-release niacin (Niaspan, Abbott Laboratories) titrated to 1.5 grams nightly for a total of 12 weeks significantly improves penetration frequency and the maintenance of an erection after penetration when compared to baseline (25913). The validity of this finding is limited by the lack of a comparator group.
• Glaucoma. It is unclear if oral niacin is beneficial for preventing or treating glaucoma. Details: Population research has found that higher dietary intake of niacin is associated with a lower odds of having glaucoma. However, this association was not consistently present when adjusting for confounders. The effects of niacin supplementation on glaucoma have not been evaluated (107942).
• Hyperphosphatemia. It is unclear if oral niacin is beneficial for preventing high levels of phosphorus in the blood. Details: Preliminary clinical research in patients on maintenance dialysis who are no longer using phosphate binders shows that taking niacin 375-750 mg daily for 8 weeks reduces serum phosphorus levels by 2.1 mg/dL, increases calcium levels by 0.4 mg/dL, and decreases serum alkaline phosphatase when compared with baseline (25914). However, clinical research in hemodialysis patients with inadequate phosphate control despite using standard phosphate-binding therapy shows that taking niacin at the maximum tolerated dose, up to 1000 mg daily, for 12 weeks, does not decrease serum phosphate levels when compared with placebo (93341). It is possible that this latter study was too small to observe between-group differences in changes in serum phosphate levels.
• Hypertension. It is unclear if dietary niacin is beneficial for preventing hypertension. Details: Observational research in Chinese adults found a J-shaped association between dietary niacin intake and development of hypertension, with the lowest risk occurring in those with a daily dietary niacin intake of 14.3-16.7 mg (104934).
• Meniere disease. Although there is interest in using oral niacin for Meniere disease, there is insufficient reliable information about the clinical effects of niacin for this condition.
• Migraine headache. It is unclear if dietary niacin is beneficial for preventing migraine headaches. Details: Population research in adults has found that high dietary intake of niacin is associated with a 28% lower likelihood of having migraine headaches when compared with low dietary intake of niacin (110495). However, the effect of niacin supplementation on migraines has not been studied.
• Motion sickness. Although there is interest in using oral niacin for motion sickness, there is insufficient reliable information about the clinical effects of niacin for this purpose.
• Parkinson disease. It is unclear if oral niacin is beneficial for improving Parkinson disease symptoms. Details: Low-quality clinical research in adults with Parkinson disease shows that taking slow-release niacin 250 mg orally daily for 12 months improves Parkinson disease motor scores and fatigue scores by 17% and 26%, respectively, when compared with baseline (107944). However, higher quality clinical research shows that taking niacin 250 mg orally daily for 6 months does not improve Parkinson disease motor scores when compared with placebo (107943).
• Retinal vein occlusion. It is unclear if oral niacin is beneficial for improving retinal vein occlusion symptoms. Details: A small case series in patients with chronic retinal vein occlusion shows that taking niacin titrated to 500 mg three times daily for 1 year is associated with reduced central macular thickness and improved visual acuity in over 50% of patients when compared with a control group. The addition of prednisolone eye drops does not alter the outcomes of those taking niacin (96212). The validity of this finding is limited due to the retrospective nature of this study.
• Sickle cell disease. It is unclear if oral niacin is beneficial for improving lipid levels in patients with sickle cell disease. Details: A small clinical study in patients with sickle cell disease shows that taking extended-release niacin titrated to 1.5 grams daily for 12 weeks does not improve vascular function or increase high-density lipoprotein (HDL) or apolipoprotein A-I cholesterol levels when compared with placebo (96209).
• Schizophrenia. Although there is interest in using oral niacin for schizophrenia, there is insufficient reliable information about the clinical effects of niacin for this condition.
• Vertigo. Although there is interest in using oral niacin for vertigo, there is insufficient reliable information about the clinical effects of niacin for this condition. More evidence is needed to rate niacin for these uses.

(Read more about NIACIN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. It is unclear if oral stevia is beneficial in patients with diabetes; the available research is conflicting. Details: A small single-dose study shows that taking stevia leaf extract 1000 mg, standardized to contain 91% stevioside, along with a meal reduces postprandial glucose levels by 18% in adults with type 2 diabetes when compared with a starch control (11812). However, clinical research in patients with type 1 or type 2 diabetes shows that taking stevioside 250 mg three times daily for 3 months does not affect blood glucose levels or glycated hemoglobin (HbA1C) when compared with baseline (16705). Also, a small clinical study in patients with diabetes shows that drinking 200 mL of black tea, sweetened with stevia extract 2%, three times daily for 8 weeks does not affect glycemic indices when compared with drinking tea sweetened with sucralose (103695).
• Hypertension. It is unclear if oral stevia is beneficial in patients with hypertension; the available research is conflicting. Details: Some clinical research in patients with mild to moderate hypertension shows that taking stevioside, a constituent of stevia, 750-1500 mg in three divided doses daily reduces systolic blood pressure by 10-14 mmHg and diastolic blood pressure by 6-14 mmHg within one week to three months of treatment initiation and continuing for up to 2 years (11809,11810). However, other clinical research in patients with mild hypertension shows that taking stevioside in doses up to 15 mg/kg daily does not significantly reduce blood pressure (16706).
• Obesity. It is unclear if oral stevia is beneficial in patients with obesity; the available research is conflicting. Details: Although a small clinical study in healthy adults shows that drinking water with stevia (Truvia) 245 ppm as a single dose reduces appetite and energy intake when compared with drinking water alone (103697), other small, single-dose studies have shown no effect of stevia 15.3 mg or 1 gram as a single dose on satiety, energy intake, or fullness when compared with either water alone or a non-nutritive sweetener (103696,110124). A small clinical study in healthy adults shows that taking an aqueous stevia leaf extract (SweetLeaf) twice daily for 12 weeks does not affect body weight, compared with an increase in weight in the control group. This suggests that stevia extract may have attenuated weight gain in this study (106458). More evidence is needed to rate stevia for these uses.

(Read more about STEVIA)

LIKELY EFFECTIVE

• Dental caries. Using xylitol-containing products topically in the mouth seems to reduce the incidence of cavities. Details: Use of xylitol-containing products such as foods, chewing gum, candies, soluble dragees, and toothpaste that provide 1-20 grams of xylitol per day can marginally reduce the incidence of cavity formation in both adults and children (6815,6819,6822,95110,95114,95116,95117,95125). Xylitol products appear to be more effective than products containing sorbitol for preventing cavity formation (6822,95690). A scientific council of the American Dental Association states that chewing gum containing xylitol for 10-20 minutes after meals, or using lozenges providing xylitol 5-8 grams in divided doses daily, can reduce the incidence of coronal caries in adults and children 5 years or older (95690). However, these recommendations are based on only weak evidence. There is not enough evidence to recommend xylitol products for preventing caries in children under the age of 5 years (95124,95690,112858). In 2008, the US Food and Drug Administration (FDA) authorized a health claim for products containing xylitol. These products can state that although frequently eating foods high in sugars and starches as between-meal snacks can promote tooth decay, xylitol used to sweeten food does not promote tooth decay and may reduce the risk of dental caries (102364).

POSSIBLY EFFECTIVE

• Otitis media. Using xylitol-containing products topically in the mouth on a daily basis seems to reduce the risk of otitis media in preschool-aged children. Details: Giving a total daily dose of xylitol 8.4-10 grams as a chewing gum, lozenge, or syrup five times a day after meals to preschool children seems to reduce the risk of acute otitis media by about 25% when compared to control (6816,6817,95112). Xylitol gum and xylitol lozenges appear to be similarly effective for this indication; xylitol syrup might be slightly less effective than xylitol gum (95111,95112). Some research suggests that xylitol may also reduce the usage of antibiotics for acute otitis media, although results are conflicting (6816,6817,95112). However, xylitol 8.4-10 grams daily, administered at the onset of symptoms of an acute respiratory infection, does not seem to prevent acute otitis media (3846,95112). Xylitol also does not appear to reduce the risk of acute otitis media among otitis-prone healthy children (95112).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Coronavirus disease 2019 (COVID-19). It is unclear if intranasal xylitol is beneficial in patients with COVID-19. Details: Preliminary clinical research in adult outpatients with a positive COVID-19 test who are receiving standard treatment for symptoms lasting less than 3 days shows that using a nasal spray containing xylitol 11%, sodium chloride 0.85%, and grapefruit seed extract 0.2% in water, 2 sprays in each nostril every 3 hours while awake for 72 hours, then every 6 hours for a total of 14 days, does not affect time to symptom resolution or incidence of hospitalization when compared with a normal saline spray (109996).
• Cystic fibrosis. It is unclear if inhaled xylitol is beneficial in patients with cystic fibrosis. Details: Preliminary clinical research in patients hospitalized for an exacerbation of cystic fibrosis shows that administering 5 mL of xylitol 15% solution through a nebulizer twice daily for 2 weeks does not improve lung function, the density of sputum microbes, or quality of life when compared with hypertonic saline (103888).
• Dental plaque. There is some evidence that chewing xylitol gum reduces oral plaque in adults. It is unclear if topical xylitol solution helps to reduce dental plaque in children or adolescents. Details: A meta-analysis of 8 studies in adults shows that chewing sugar-free gum containing xylitol, sorbitol, or maltitol reduces oral plaque levels when compared with chewing sugar-containing gum or not chewing any gum (109997). One small clinical study in children aged 2-5 years shows that applying 40% xylitol solution using gauze once daily for 6 months does not suppress Streptococcus mutans count or reduce plaque accumulation when compared to baseline (95119). Conversely, a small clinical study in adolescents aged 14-17 years shows that rinsing with a solution containing xylitol, lysozyme, sea salt, and menthol (H2Ocean Sea Salt Mouthwash) twice daily for 3 months seems to reduce dental plaque and S. mutans levels when compared to baseline (105979). The validity of this finding is limited due to a lack of statistical comparison to the placebo group. Additionally, it is unclear if any effects are due to xylitol, other ingredients, or the combination.
• Dry mouth. Oral xylitol has only been evaluated in combination with maltitol; its effect when used alone is unclear. Details: One small open-label clinical study in patients with gastroesophageal reflux disease who are experiencing dry mouth while taking omeprazole 40 mg daily shows that taking specific tablets (Xeros Dentaid, Dentaid) containing xylitol 422 mg and malic acid 28.6 mg 3 times daily after meals for 6 months seems to reduce the incidence of dry mouth and increase the buffering capacity of saliva when compared with no additional treatment (105982).
• Gingivitis. Topical xylitol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study of patients with gingivitis shows that brushing with a toothpaste containing a combination of xylitol, extra virgin olive oil, and betaine anhydrous daily for 4 months decreases gingival bleeding and improves markers associated with gingival health when compared with placebo and commercial toothpaste (111372).
• Gulf war syndrome. It is unclear if intranasal xylitol is beneficial for improving respiratory symptoms in adults with Gulf war syndrome. Details: A small clinical study in patients with chronic rhinosinusitis and Gulf war syndrome shows that administering xylitol 5% solution intranasally via neti pot twice daily for 26 weeks in addition to standard care modestly improves nasal symptoms when compared with standard treatment alone. However, the improvement did not reach the pre-specified measure of clinical significance (105981).
• Hematopoietic stem cell transplant (HSCT). It is unclear if topical xylitol dental wipes help to prevent infections after HSCT. Details: One small open-label clinical trial in children and young adults undergoing HSCT shows that adding xylitol dental wipes 0.7 grams daily to standard care for oral hygiene, starting with ablative chemotherapy and continuing 28 days post-transplant, reduces the risk for bloodstream infections when compared with standard care alone. For every 4 patients treated with xylitol, one bloodstream infection was prevented (103890).
• Intranasal surgery. It is unclear if nasal irrigation with xylitol solution improves pain and obstruction after intranasal surgery. Details: Preliminary clinical research in patients undergoing endonasal endoscopic surgery shows that nasal irrigation with 60 mL of solution containing xylitol 1 gram in each nostril three times daily for 30 days, starting the second day after surgery, reduces pain and nasal obstruction when compared with saline nasal irrigation (103889).
• Postoperative ileus. It is unclear if chewing xylitol gum can reduce the development of postoperative ileus after various types of surgery. Details: An unblinded clinical study in adults undergoing colorectal resection for colon cancer shows that chewing xylitol gum for 15 minutes three times daily, starting on the first postoperative day, reduces the time to first flatus from 53 hours to 39 hours and the time to first defecation from 78 hours to 55 hours when compared with standard care alone (109998). A small clinical study in patients undergoing a Cesarean section shows that chewing xylitol gum for 15 minutes every 2 hours for 8-12 hours, starting 2 hours after surgery, does not reduce the time to first bowel sounds or first feeling of hunger when compared with chewing non-xylitol gum or not chewing any gum. The time to first defecation is 38, 44, and 45 hours, respectively, while times to hospital discharge are 46, 50, and 52 hours, respectively; it is unclear if these differences are statistically significant (109999).
• Rhinosinusitis. Small clinical studies suggest that intranasal rinses with xylitol solution may modestly improve nasal symptoms in patients with chronic rhinosinusitis. Details: Two small clinical studies in patients with chronic rhinosinusitis shows that nasal irrigation using 240 mL of solution containing xylitol 12 grams daily for up to 30 days reduces symptoms better than nasal irrigation with saline (95115,95122). Another small clinical study in patients with chronic rhinosinusitis and Gulf war syndrome shows that administering xylitol 5% solution intranasally via neti pot twice daily for 26 weeks in addition to standard care modestly improves nasal symptoms when compared with standard treatment alone. However, the improvement did not reach the pre-specified measure of clinical significance (105981). More evidence is needed to rate xylitol for these uses.

(Read more about XYLITOL)

Some alpha hydroxy acids are used topically, while others are used orally, intravaginally, or by inhalation. See specific monographs for safety information.

PREGNANCY AND LACTATION:
See specific monographs for safety information.

(Read more about ALPHA HYDROXY ACIDS (AHAs))

POSSIBLY SAFE ...when used orally and appropriately, short-term. Deer velvet powder has been used with apparent safety at a dose of 1-1.5 grams daily for up to 10-12 weeks (47106,47108).

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

(Read more about DEER VELVET)

LIKELY SAFE ...when niacin is taken in food or as a supplement in amounts below the tolerable upper intake level (UL) of 30 mg daily for adults 18 years of age and 35 mg daily for adults 19 years and older (6243). ...when prescription products are used orally and appropriately in doses of up to 2 grams daily (12033). CHILDREN:

LIKELY SAFE ...when used orally in amounts that do not exceed the tolerable upper intake level (UL). The ULs of niacin for children are: 1-3 years of age, 10 mg daily; 4-8 years of age, 15 mg daily; 9-13 years of age, 20 mg daily; 14-18 years of age, 30 mg daily (6243).

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

(Read more about NIACIN)

LIKELY SAFE ...when certain stevia constituents, including stevioside and rebaudiosides A, D, and M, are used orally as sweeteners in foods. These constituents have generally recognized as safe (GRAS) status in the US for this purpose (16699,16700,16702,16705,16706,108049). The stevia constituent stevioside has been safely used in doses of up to 1500 mg daily for 2 years (11809,11810,11811). There is insufficient reliable information available about the safety of whole stevia or stevia extracts when used orally. The European Food Safety Authority (EFSA) has determined that the acceptable intake of steviol glycosides is 4 mg/kg daily (106456); however, it is unclear how this relates to the use of whole stevia or stevia extract.

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

(Read more about STEVIA)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Xylitol is an approved food additive in the US (17915).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts as a chewing gum, candy, lozenge, toothpaste, or mouth rinse. Xylitol has been used with apparent safety in doses of 20-53 grams daily for up to 3 years (6815,6819,6821). ...when used as nasal irrigation 1-3 times daily for up to 30 days (95115,95122,103889,105981). ...when inhaled via nebulizer. 5 mL of xylitol 15% solution has been used with apparent safety twice daily for up to 2 weeks (103888).

POSSIBLY UNSAFE ...when used orally in very high doses, long-term. There is some concern that very high doses for extended periods of use can induce tumor growth (6815,6820). However, this effect has not yet been demonstrated in humans.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in medicinal amounts as a chewing gum, candy, lozenge, toothpaste, or mouth rinse. Xylitol has been used with apparent safety in doses up to 20 grams daily for up to three years (6815,6819).

PREGNANCY AND LACTATION:
There insufficient reliable information available about the use of xylitol in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about XYLITOL)

(Read more about ALPHA HYDROXY ACIDS (AHAs))

CONTRACEPTIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, deer velvet might interfere with the effectiveness of contraceptive drugs.  Details Laboratory research shows that deer velvet contains small quantities of estradiol and testosterone (47110). While clinical research shows that taking deer velvet extract does not raise testosterone levels, estradiol levels were not measured (47108).

ESTROGENS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, deer velvet might increase the effects and side effects of estrogens.  Details Laboratory evidence shows that deer velvet contains small quantities of estradiol and testosterone (47110). While clinical research shows that taking deer velvet extract does not raise testosterone levels, estradiol levels were not measured (47108).

(Read more about DEER VELVET)

ALCOHOL (Ethanol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.  Details Alcohol can exacerbate the flushing and pruritus associated with niacin (4458,11689). Large doses of niacin might also exacerbate liver dysfunction associated with chronic alcohol use. A case report describes delirium and lactic acidosis in a patient taking niacin 3 grams daily who ingested 1 liter of wine (14510). Advise patients to avoid large amounts of alcohol while taking niacin.

ALLOPURINOL (Zyloprim) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol.  Details Large doses of niacin can reduce urinary excretion of uric acid, potentially resulting in hyperuricemia (4860,4863,12033). Doses of uricosurics such as allopurinol might need to be increased to maintain control of gout in patients who start taking niacin (4458). People who have frequent attacks of gout despite uricosuric therapy should avoid niacin (4863).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.  Details Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin (25915). Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin (25916).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs.  Details Niacin impairs glucose tolerance in a dose-dependent manner, probably by causing or aggravating insulin resistance and increasing hepatic production of glucose (4860,4863,11692,11693). In diabetes patients, niacin 4.5 grams daily for 5 weeks can increase plasma glucose by an average of 16% and glycated hemoglobin (HbA1c) by 21% (4860). However, lower doses of 1.5 grams daily or less appear to have minimal effects on blood glucose (12033). In some patients, glucose levels increase when niacin is started, but then return to baseline when a stable dose is reached (12033,93344). Up to 35% of patients with diabetes may need adjustments in hypoglycemic therapy when niacin is added (4458,4860,4863,11689,12033).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs.  Details The vasodilating effects of niacin can cause hypotension (4863,12033,93341). Furthermore, some clinical evidence suggests that a one-hour infusion of niacin can reduce systolic, diastolic, and mean blood pressure in hypertensive patients. This effect is not observed in normotensive patients (25917).

ASPIRIN Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Likely •  Level of Evidence = B Large doses of aspirin might alter the clearance of niacin.  Details Aspirin is often used with niacin to reduce niacin-induced flushing (4458,11689). Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal (4458,4852,4853,11689). Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45% (14524). This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg (11689,14524).

BILE ACID SEQUESTRANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction.  Details In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30% (14511).

GEMFIBROZIL (Lopid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients.  Details A case of myopathy from concomitant use of niacin and gemfibrozil has been reported (25920). Niacin alone has also been associated with cases of myopathy (26100,26111). Using gemfibrozil with niacin might further increase the risk of developing myopathy.

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.  Details Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses (4863,11689,11691,25929,25930,25931). Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin (11691,25930,25931,93342).

HMG-CoA REDUCTASE INHIBITORS ("Statins") Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients.  Details Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins (14508,25918). However, a significantly increased risk of myopathy has not been demonstrated in clinical trials, including those using an FDA-approved combination of lovastatin and niacin (Advicor) (7388,11689,12033,14509).

PROBENECID (Benemid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid.  Details Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia (4863,12033). Doses of uricosurics such as probenecid might need to be increased to maintain control of gout in patients who start taking niacin (4458). People who have frequent attacks of gout despite uricosuric therapy should avoid niacin (4863).

SULFINPYRAZONE (Anturane) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone.  Details Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia (4863,12033). Doses of uricosurics such as sulfinpyrazone might need to be increased to maintain control of gout in patients who start taking niacin (4458). People who have frequent attacks of gout despite uricosuric therapy should avoid niacin (4863).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones.  Details Clinical research and case reports suggests that taking niacin can reduce serum levels of thyroxine-binding globulin by up to 25% and moderately reduce levels of thyroxine (T4) (25916,25925,25926,25928). Patients taking thyroid hormone for hypothyroidism might need dose adjustments when using niacin.

TRANSDERMAL NICOTINE (Nicoderm) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of niacin and transdermal nicotine might increase the risk of flushing and dizziness.  Details Niacin and nicotine can both cause flushing and dizziness (496,96211).

(Read more about NIACIN)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might increase the risk for hypoglycemia when combined with antidiabetes drugs.  Details Preliminary clinical research in patients with type 2 diabetes suggests that taking a single dose of stevia extract 1000 mg reduces postprandial blood glucose levels when taken with a meal (11812). However, other clinical research in patients with type 1 or type 2 diabetes suggests that taking stevioside 250 mg three times daily does not significantly affect blood glucose levels or glycated hemoglobin (HbA1C) after three months of treatment (16705).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining stevia or stevia constituents with antihypertensive agents might increase the risk of hypotension.  Details Stevia extract and stevioside might lower blood pressure in patients with hypertension (3745,3747,5031,11809,11810). However, other clinical research suggests that stevioside does not significantly lower blood pressure in patients with hypertension (16706).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, stevia might decrease clearance and increase levels of lithium.  Details Animal research suggests that stevia extracts might have diuretic activity (3746,3747). Theoretically, increased reabsorption of lithium along with sodium might reduce excretion and increase levels of lithium.

(Read more about STEVIA)

(Read more about XYLITOL)

General ...Alpha hydroxy acids represent a group of natural chemicals, some of which can cause adverse effects. See specific monographs for safety information.

(Read more about ALPHA HYDROXY ACIDS (AHAs))

General ...Orally, deer velvet powder or extract seems to be well tolerated, short-term. However, a thorough evaluation of safety outcomes has not been conducted.

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General ...Orally, niacin is well tolerated in the amounts found in foods. It is also generally well tolerated in prescription doses when monitored by a healthcare provider.
Most Common Adverse Effects:
Orally: Flushing, gastrointestinal complaints (abdominal pain, constipation, diarrhea, heartburn, nausea, vomiting), and elevated liver enzymes.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity, myopathy, thrombocytopenia, and vision changes.

Cardiovascular ...Orally, flushing is a common dose-related adverse reaction to niacin. A large meta-analysis of clinical studies shows that up to 70% of patients may experience flushing (96211). Although flushing can occur with doses of niacin as low as 30 mg daily, it is more common with the larger doses used for treatment of dyslipidemia. The flushing reaction is due to prostaglandin-induced blood vessel dilation and can also include symptoms of burning, tingling, urticaria, erythema, pain, and itching of the face, arms, and chest. There may also be increased intracranial blood flow and headache (4889,26089,93341,104933). Onset is highly variable and ranges from within 30 minutes to as long as 6 weeks after the initial dose (6243). Flushing can be minimized via various strategies, including taking doses with meals, slow dose titration, using extended release formulations, pretreating with non-steroidal anti-inflammatory drugs, taking regular-release niacin with meals, or taking the sustained-release product at bedtime (4852,4853,4854,4857,4858,25922,26073,26084). Flushing often diminishes with continued use but can recur when niacin is restarted after missed doses (4863,6243,26081). The vasodilating effects of niacin can also cause hypotension, dizziness, tachycardia, arrhythmias, syncope, and vasovagal attacks, especially in patients who are already taking antihypertensive drugs (4863,12033,93341,110494).
High doses of niacin can raise homocysteine levels. A 17% increase has been reported with 1 gram daily and a 55% increased has been reported with 3 grams daily. Elevated homocysteine levels are an independent risk factor for cardiovascular disease (490); however, the clinical significance of this effect is unknown. A large-scale study (AIM-HIGH) found that patients receiving extended-release niacin (Niaspan) 1500-2000 mg daily with a statin had an over two-fold increased risk of ischemic stroke (1.6%) when compared with those receiving only simvastatin (0.7%). However, when the risk was adjusted for confounding factors, niacin was not found to be associated with increased stroke risk (17627,93354). A meta-analysis of three clinical trials conducted in approximately 29,000 patients showed a higher risk of mortality in patients taking niacin in addition to a statin when compared with a statin alone. However, with a p-value of 0.05 and confidence interval including 1, the validity of this finding remains unclear (97308).

Endocrine ...Orally, niacin can impair glucose tolerance in a dose-dependent manner. Dosages of 3-4 grams daily appear to increase blood glucose in patients with or without diabetes, while dosages of 1.5 grams daily or less have minimal effects (12033). Niacin is thought to impair glucose tolerance by increasing insulin resistance or increasing hepatic output of glucose (4863,11692,11693). In patients with diabetes, niacin 4.5 grams daily for 5 weeks has been associated with an average 16% increase in plasma glucose and 21% increase in glycated hemoglobin (HbA1C) (4860). Up to 35% of patients with diabetes may need to increase the dose or number of hypoglycemic agents when niacin is started (4458,4860,4863,11689,12033). Occasionally, severe hyperglycemia requiring hospitalization can occur (11693). In patients with impaired fasting glucose levels, niacin may also increase fasting blood glucose, and adding colesevelam might attenuate this effect (93343).
Although patients without diabetes seem to only experience small and clinically insignificant increases in glucose (4458), niacin might increase their risk of developing diabetes. A meta-analysis of clinical research involving over 26,000 patients shows that using niacin over 5 years is associated with increased prevalence of new onset type 2 diabetes at a rate of 1 additional case of diabetes for every 43 patients treated with niacin (96207). This finding is limited because the individual trials were not designed to assess diabetes risk and the analysis could not be adjusted for confounding factors like obesity. One small clinical study shows that taking extended-release niacin with ezetimibe/simvastatin does not increase the risk of a new diagnosis of diabetes or need for antidiabetic medication when compared with ezetimibe/simvastatin alone after 16 months (93344). This may indicate that the increased risk of developing diabetes is associated with niacin use for more than 16 months.
Niacin therapy has also been linked with hypothyroidism and its associated alterations in thyroid hormone and binding globulin tests (such as decreased total serum thyroxine, increased triiodothyronine, decreased thyroxine-binding globulin levels, and increased triiodothyronine uptake) (25916,25925,25926,25928).

Gastrointestinal ...Orally, large doses of niacin can cause gastrointestinal disturbances including nausea, vomiting, bloating, heartburn, abdominal pain, anorexia, diarrhea, constipation, and activation of peptic ulcers (4458,4863,12033,26083,93341,96211). These effects may be reduced by taking the drug with meals or antacid, and usually disappear within two weeks of continued therapy (4851,26094). Gastrointestinal effects may be more common with time-release preparations of niacin (11691).

Hematologic ...Orally, sustained-release niacin has been associated with cases of reversible coagulopathy, mild eosinophilia, and decreased platelet counts (4818,25915,26097,93340). Also, there have been reports of patients who developed leukopenia while taking niacin for the treatment of hypercholesterolemia (25916).

Hepatic ...Orally, niacin is associated with elevated liver function tests and jaundice, especially with doses of 3 grams/day or more, and when doses are rapidly increased (4458,4863,6243). The risk of hepatotoxicity appears to be higher with slow-release and extended-release products (4855,4856,4863,6243,11691,12026,12033,93342). Niacin should be discontinued if liver function tests rise to three times the upper limit of normal (4863). There are rare cases of severe hepatotoxicity with fulminant hepatitis and encephalopathy due to niacin (4863,6243,11691). Also, there is at least one case of niacin-induced coagulopathy resulting from liver injury without liver enzyme changes (93340).

Musculoskeletal ...Orally, niacin has been associated with elevated creatine kinase levels (4818,4888). Also, several cases of niacin-induced myopathy have been reported (26100,26111). Concomitant administration of niacin and HMG-CoA reductase inhibitors may increase the risk of myopathy and rhabdomyolysis (14508,25918,26111); patients should be monitored closely.

Neurologic/CNS ...Orally, high-dose niacin has been associated with cases of neuropsychiatric adverse events such as extreme pain and psychosis. Two 65-year-old males taking niacin orally for 5 months for the treatment of dyslipidemias developed severe dental and gingival pain. The pain was relieved by the discontinuation of niacin. The pain was thought to be due to inflammation and pain referral to the teeth (4862). In one case report, a 52-year-old male with no history of psychiatric illness who initially complained of hot flushes when taking niacin 500 mg daily, presented with an acute psychotic episode involving mania after niacin was increased to 1000 mg daily (93350).

Ocular/Otic ...Orally, chronic use of large amounts of niacin has been associated with dry eyes, toxic amblyopia, blurred vision, eyelid swelling, eyelid discoloration, loss of eyebrows and eyelashes, proptosis, keratitis, macular edema, and cystic maculopathy, which appear to be dose-dependent and reversible (4863,6243,26112).

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General ...Orally, stevia and steviol glycosides appear to be well tolerated. Most minor adverse effects seem to resolve after the first week of use.
Most Common Adverse Effects:
Abdominal bloating, dizziness, headache, myalgia, nausea, and numbness.
Serious Adverse Effects (Rare):
Allergic reactions.

Gastrointestinal ...Orally, stevia and steviol glycosides such as stevioside, can cause gastrointestinal adverse effects such as abdominal fullness and nausea. However, these generally resolve after the first week of use (11809,11810).

Immunologic ...Theoretically, stevia might cause allergic reactions in individuals sensitive to plants in the Asteraceae/Compositae family (11811). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, stevia and steviol glycosides may cause myalgia, but this generally resolves after the first week of use (11809,11810).

Neurologic/CNS ...Orally, stevia and steviol glycosides may cause headache, dizziness, and numbness (11809,11810).

(Read more about STEVIA)

General ...Orally, xylitol is generally well tolerated in food amounts, although it may cause gastrointestinal discomfort at high doses. Topically, xylitol seems to be well tolerated.
Most Common Adverse Effects:
Orally: With high doses (30-40 grams), bowel sounds, diarrhea, flatulence.
Topically: Stinging of mucous membranes.

Endocrine ...Orally, high doses of xylitol can increase the risk of hyperuricemia. In a small study in healthy adults, taking a single dose of xylitol 35 grams in water increases levels of uric acid, while lower doses of xylitol did not have this effect (105980). Intravenous infusion of high doses of xylitol has been associated with hyperuricemia and acidosis, including lactic acidosis (6815).

Gastrointestinal ...Orally, acute administration of large amounts of xylitol (30 to 40 grams) can cause osmotic diarrhea, nausea, and flatulence (9,112857). However, if the dose is increased gradually, tolerance to this effect can occur and prevent development of diarrhea and flatulence (9).

Hepatic ...Intravenous infusion of high doses has been associated with changes in liver function enzymes (6815).

Immunologic ...There are various cases of suspected allergic reactions to xylitol. In one case, an anaphylactic reaction to xylitol was reported in a 2-year-old. The allergy was confirmed based on a skin-prick test and basophil activation test (100173).

Pulmonary/Respiratory ...Following use of xylitol in nasal irrigation, minor stinging in the nose has been reported (95122,105981).

(Read more about XYLITOL)