B-12 Gold 1,800 mcg [Discontinued] by NutriGold

POSSIBLY INEFFECTIVE

• Hypercholesterolemia. Preliminary clinical research shows that eating muffins made with amaranth flour or taking oral doses of amaranth oil 3-18 mL daily while following a reduced fat diet for 3-4 weeks does not reduce serum cholesterol levels more than the reduced fat diet alone (6188,31069). Similarly, two clinical trials in overweight and obese adults show that taking amaranth oil 20 mL daily for 3 weeks does not decrease low-density lipoprotein (LDL) cholesterol or triglyceride levels or increase high-density lipoprotein (HDL) cholesterol levels when compared with either rapeseed oil 20 mL daily or no intervention (104834,104837). In one of these trials, amaranth oil 20 mL increased LDL levels when compared to baseline (104834).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Iron deficiency anemia. Preliminary clinical research in children shows that consuming 150 grams of bread made with 70% amaranth grain, providing approximately 22.3 mg iron, for 6 months decreases the prevalence of anemia by 61% and increases hemoglobin levels by 8% when compared with consuming bread containing 100% maize grain. The amaranth used in this study was processed to reduce phytic acid content in order to improve iron absorption (104835).
• Peptic ulcers. Preliminary clinical research shows that taking amaranth oil from Amaranthus cruentus seeds 1 mL daily for 27 days immediately following standard treatment with lansoprazole, amoxicillin, and clarithromycin for 7 days does not improve clinical outcomes with Helicobacter pylori-associated peptic ulcers more than standard treatment alone (99235). More evidence is needed to rate amaranth for these uses.

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POSSIBLY EFFECTIVE

• Colorectal cancer. Consumption of cruciferous vegetables, including broccoli, seems to reduce the risk of developing colorectal cancer. Details: Epidemiological research suggests that the highest intakes of cruciferous vegetables, including broccoli, are associated with an 18% to 20% reduced risk of developing colorectal neoplasms when compared with the lowest intakes (14148,96187,96189).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bladder cancer. It is unclear if consumption of broccoli reduces the risk of developing bladder cancer. Details: Epidemiological research suggests that eating about 1.75 cups daily of cruciferous vegetables, such as broccoli or cabbage, is associated with a 30% reduced risk of developing bladder cancer (14864).
• Breast cancer. It is unclear if consumption of broccoli reduces the risk of developing breast cancer. Details: Epidemiological research suggests that consumption of broccoli is associated with a modestly reduced risk of developing breast cancer in premenopausal adults. However, broccoli consumption does not seem to be associated with breast cancer risk in postmenopausal adults (14146).
• Fibromyalgia. Broccoli has only been evaluated in combination with ascorbigen; its effect when used alone is unclear. Details: A small clinical study in females with fibromyalgia shows that taking one capsule containing ascorbigen 100 mg and broccoli powder 400 mg once daily for one month improves pain by 18% and reduces physical impairment by 20% when compared to baseline (19605). It is unclear if this effect is due to broccoli, ascorbigen, or the combination. The validity of these findings is limited by the lack of a comparator group.
• Gastric cancer. It is unclear if consumption of broccoli reduces the risk of developing gastric cancer. Details: A small epidemiological study suggests that higher consumption of broccoli is associated with a reduced risk of developing gastric cancer when compared with lower consumption (14148).
• Helicobacter pylori. It is unclear if consumption of broccoli is beneficial for treating Helicobacter pylori infection. Details: A moderate-sized clinical study in adults with Helicobacter pylori infection shows that taking broccoli seed extract 200 mg, containing 16% glucosinolates, daily before bedtime for 2 months does not improve Helicobacter pylori eradication rate when compared with placebo (112445,112446).
• Hypercholesterolemia. Broccoli has only been evaluated in combination with cabbage; its effect when used alone is unclear. Details: A small clinical study in patients with mild to moderate hypercholesterolemia shows that consuming 160 grams of a beverage containing broccoli, cabbage, and fruit twice daily for 12 weeks reduces levels of low-density lipoprotein (LDL) cholesterol by 8.5% when compared to baseline. It is unclear if the improvement from baseline differed when compared with those consuming a similar beverage without broccoli and cabbage (19607). It is unclear if this effect is due to broccoli, other ingredients, or the combination.
• Hypertension. It is unclear if consumption of broccoli can prevent hypertension in healthy adults. Details: A meta-analysis of 3 prospective cohort studies in healthy adults suggests that eating 100 grams of broccoli daily is associated with a 12% reduced risk of hypertension. However, 2 other studies in the meta-analysis suggest that broccoli, consumed as part of a larger group of cruciferous vegetables, is associated with an 11% increased risk of hypertension per 100 grams eaten daily (112087).
• Prostate cancer. It is unclear if consumption of broccoli reduces the risk of developing prostate cancer; the available research is conflicting. In patients with prostate cancer, broccoli has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some epidemiological research suggests that consumption of Brassica vegetables, such as broccoli, Brussels sprouts, cauliflower, and cabbage, is associated with a reduced risk of developing prostate cancer (14145). However, other epidemiological research has found no association (14147,15172). Clinical research in adults with prostate cancer shows that taking a whole food formulation containing broccoli powder 100 mg, turmeric powder 100 mg, pomegranate whole fruit powder 100 mg, and green tea extract 20 mg three times daily for 6 months prevents an increase in prostate specific antigen (PSA) levels. Mean PSA levels increased by 15% in the whole food formulation group, compared with 79% in the placebo group. Also, 46% of those taking the whole food formulation showed final PSA levels that were the same or lower than initial PSA levels, compared with 14% of those in the placebo group (89730). However, it is not yet known whether the whole food formulation reduces the risk of prostate cancer progression or recurrence. It is unclear if these effects are due to broccoli, other ingredients, or the combination. More evidence is needed to rate broccoli for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cardiovascular disease (CVD). A meta-analysis of clinical research shows that taking buckwheat seems to improve some, but not all, markers of CVD risk. Buckwheat was found to decrease total cholesterol by 19 mg/dL, triglycerides by 22 mg/dL, and blood glucose by 15 mg/dL, but had no effect on blood pressure, body weight, insulin, or low-density lipoprotein (LDL) cholesterol when compared with a control group (100947). The patient populations included in this analysis ranged from healthy adults to those with diabetes or hyperlipidemia; it's unclear whether the results are consistent across patient groups or if the benefits are more pronounced in certain types of patients. The effects of buckwheat on cardiovascular events, such as myocardial infarction, stroke, or cardiovascular death, in patients with CVD, are unknown.
• Chronic venous insufficiency (CVI). Preliminary clinical research shows that drinking common buckwheat tea for 3 months attenuates leg swelling compared with placebo in patients with chronic venous insufficiency (37351).
• Diabetes. Preliminary clinical research shows that patients with type 2 diabetes who replace a portion of white rice or white flour with tartary buckwheat 50 grams three times daily for 4 weeks show a 3% reduction in fasting insulin and a 7% reduction in low-density lipoprotein (LDL) cholesterol compared to baseline. Patients who consume the standardized recipe containing white rice and/or white flour three times daily for 4 weeks show no significant changes in these measurements. Neither groups show improvement in fasting blood glucose or hemoglobin A1c levels (96063).
• Diabetic retinopathy. Preliminary clinical research shows that taking common buckwheat 1 gram three times daily for 3 months does not significantly improve visual acuity compared with baseline in patients with diabetic retinopathy (37358). More evidence is needed to rate the effectiveness of buckwheat for these uses.

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POSSIBLY INEFFECTIVE

• Hyperlipidemia. A meta-analysis of small clinical studies suggests that consuming chia seeds, flour, powder, or oil for 7-24 weeks does not improve lipid levels in patients with conditions associated with hyperlipidemia. Details: A meta-analysis of 10 small clinical trials in patients with various metabolic conditions, including diabetes, metabolic syndrome, nonalcoholic fatty liver disease, and obesity, shows that consuming chia seeds, flour, or powder 15-60 grams daily for 7-24 weeks, or taking chia oil 6 grams daily for 8 weeks, does not reduce total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglyceride levels or increase high-density lipoprotein (HDL) cholesterol levels when compared with control groups consuming wheat bran, oat bran, dietary fiber, poppy seeds, or soybean oil (106657). While the patient populations in the studies analyzed are more likely to develop hyperlipidemia, it is unclear if these findings can be generalized to patients diagnosed with hyperlipidemia.
• Obesity. Small clinical studies suggest that consuming chia seeds for up to 12 weeks does not reduce body weight in overweight or obese adults. Details: One small clinical study in overweight or obese individuals shows that ingesting chia seeds 25 grams mixed in 0.25 liters of water twice daily before meals for 12 weeks does not improve body composition or reduce blood pressure when compared with placebo (25533). Another small clinical study in overweight, postmenopausal females shows that ingesting milled or whole chia seeds 25 grams daily for 10 weeks does not improve body composition or blood pressure when compared to baseline (25532).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral chia is beneficial for improving athletic performance. Details: A small clinical study in trained athletes shows that drinking a beverage containing 50% of calories from chia seeds (Greens Plus Omega 3 Chia seeds) and 50% of calories from a carbohydrate-containing beverage (Gatorade) for 2 days prior to participating in an endurance exercise lasting more than 90 minutes leads to similar performance when compared with Gatorade alone (25531).
• Cardiovascular disease (CVD). Although there has been interest in using oral chia for CVD, there is insufficient reliable information about the clinical effects of chia for this purpose.
• Diabetes. Small clinical studies suggest that consuming chia for 4-6 months might reduce systolic blood pressure (SBP) in patients with type 2 diabetes, although it does not appear to improve glycemic control or lipid levels and has shown mixed effects on body weight and inflammatory markers. Details: One small clinical trial in patients with type 2 diabetes shows that consuming bread containing a specific, selectively bred type of chia (Salba, Salba Smart Natural Products LLC), providing 37 grams of chia daily for 12 weeks reduces SBP, C-reactive protein, and vonWillebrand factor, but not lipid levels, when compared with consuming bread containing wheat bran. This form of chia also significantly reduced glycated hemoglobin (HbA1c) when compared to baseline, but not when compared with a wheat bran control (16124). Another small clinical study in adults with type 2 diabetes and obesity shows that consuming Salba chia 40 grams daily, either baked into bread or as a powder, in conjunction with a restricted calorie diet for 6 months reduces weight by 1.6 kg and waist circumference by 2.8 cm when compared with an oat bran control. However, consuming chia had no effect on body fat percentage, HbA1c, or fasting glucose levels (97940). Also, a small clinical study in adults with type 2 diabetes shows that consuming chia seeds 40 grams daily for 12 weeks reduces SBP, but does not improve body weight, HbA1c, or levels of fasting glucose, lipids, or C-reactive protein, when compared with those not consuming chia (106658).
• Hypertension. It is unclear if oral chia is beneficial in patients with hypertension. Details: A very small clinical study in patients with mild hypertension shows that consuming chia flour 35 grams daily for 12 weeks reduces systolic blood pressure (SBP) by around 10 mm Hg and diastolic blood pressure (DBP) by almost 9 mm Hg when compared to baseline. In patients already taking antihypertensive drugs, chia seems to have an even greater impact on SBP and DBP. However, in patients not being treated with antihypertensive drugs, chia flour modestly reduces SBP by 6.5%, but does not significantly reduce DBP. No improvements in blood pressure were reported in patients consuming a wheat bran control (91516).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral chia is beneficial in patients with NAFLD. Details: Small, uncontrolled clinical studies in patients with NAFLD show that consuming milled chia seeds 25 grams daily for 8 weeks may reduce hepatic steatosis, as measured by the liver: spleen attenuation ratio, in up to 43% of subjects with prediabetes and 100% of subjects with diabetes when compared to baseline. Chia seed supplementation may also modestly reduce visceral fat, body mass index, and waist circumference in patients with prediabetes when compared to baseline, but does not seem to improve lipid levels (104530,110438). The validity of these findings is limited by the lack of a comparator group in both studies.
• Metabolic syndrome. Oral chia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with metabolic syndrome shows that reducing daily caloric intake by 500 kcal and drinking a beverage containing chia seed 4 grams, soy protein 32 grams, dehydrated nopal 7 grams, and oat 22 grams daily for 2 months reduces body weight, body mass index, and waist circumference when compared to baseline, but not when compared with following a reduced calorie diet alone. However, following the reduced calorie diet and drinking this beverage appears to lower serum triglycerides and C-reactive protein and improve glucose tolerance when compared with a reduced calorie diet alone (25534). It is unclear if these findings are due to chia, other ingredients, or the combination.
• Muscle strength. It is unclear if oral chia is beneficial for increasing muscle strength and muscle mass during resistance training. Details: A very small clinical trial in healthy, non-resistance trained males shows that drinking a supplemental beverage containing chia flour 50 grams, providing 20 grams of protein and 3 grams of omega-3 fatty acids, is no more effective than whey protein 20 grams or placebo for augmenting the increases in muscle strength and fat-free mass that occur with an 8-week whole body resistance training program (112385). The habitual baseline diet of the study participants already contained dietary protein intakes recommended for strength training, and the beverage was only consumed three times per week immediately after training sessions.
• Pruritus. It is unclear if topical chia seed oil is beneficial in patients with pruritus. Details: One very small, uncontrolled clinical study in patients with xerotic pruritus or pruritus caused by kidney failure or diabetes shows that applying lotion containing chia seed oil 4% for 8 weeks improves skin hydration and reduces the severity of lichen simplex chronicus and prurigo nodularis when compared to baseline (25537). The validity of these findings is limited by the small study size and lack of a comparator group. More evidence is needed to rate chia for these uses.

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POSSIBLY EFFECTIVE

• Constipation. Oral flaxseed is a bulk forming laxative that helps to relieve constipation. Details: Flaxseed is a source of dietary fiber and has a bulk forming laxative effect (6803,12910). One clinical study in healthy young adults shows that consuming muffins containing 25 grams of milled flaxseed twice daily for 4 weeks increases weekly bowel movements by 30% when compared to a control group (6803). Other clinical research in diabetic patients with constipation shows that taking flaxseed 10 grams twice daily for 12 weeks improves stool form and reduces constipation by a moderate amount when compared with placebo (101950). Furthermore, a small clinical study in patients in China with functional constipation shows that consuming brown flaxseed flour 50 grams in divided doses with meals daily for 4 weeks seems to modestly improve frequency of bowel movements and pain and reduce failure to evacuate when compared with taking lactulose 15 mL every morning (105474). Flaxseed has also been evaluated in combination with other natural ingredients. A preliminary clinical trial in elderly patients with mild constipation shows that eating yogurt containing galacto-oligosaccharide syrup (Elixor, Borculo Whey Products) 6 grams, prunes 6 grams, and flaxseed 3 grams twice daily for 3 weeks increases stool frequency when compared with a control yogurt (21191). It is unclear if the effects were due to flaxseed, other constituents, or the combination.
• Diabetes. Oral ground flaxseed modestly reduces blood glucose in patients with diabetes and pre-diabetes. It is unclear if oral whole flaxseed reduces blood glucose. Details: Most evidence from meta-analyses and clinical research in adults with prediabetes and diabetes shows that taking ground flaxseed reduces fasting blood glucose and insulin levels (21194,21196,26479,101950,111061). A meta-analysis of 7 small to moderate clinical trials shows that taking flaxseed, usually ground, 13 to 40 grams daily for 8-12 weeks has a small beneficial effect on fasting blood glucose, insulin, insulin resistance, and glycated hemoglobin (HbA1c), compared with no intervention or another fiber source. A sub-analysis shows that the benefit of flaxseed on fasting glucose levels remains in patients with type 2 diabetes (111061). Other research disagrees. A meta-analysis of three small clinical trials in patients with type 2 diabetes shows that taking flaxseed does not improve fasting blood glucose, insulin resistance, or HbA1c (111062). Another meta-analysis of 24 clinical studies involving 1,879 patients with and without diabetes shows that whole and ground flaxseed seem to reduce blood glucose levels by an average of 6 mg/dL and insulin levels by an average of 1 mIU/mL and modestly reduce insulin resistance when compared with control treatments such as wheat germ or raw rice. Whole and ground flaxseed were not shown to significantly reduce HbA1c when compared with control, although there was a non-significant trend towards a reduction (96428). Significant heterogeneity in study size and study population limit the validity of these findings. The effects of flaxseed lignan extract in patients with type 2 diabetes is unclear. A small clinical study in Chinese adults with type 2 diabetes show that using a specific standardized flaxseed lignan extract (Flax Essence, Jarrow Formulas) 600 mg three times daily, providing 360 mg secoisolariciresinol diglucoside, slightly reduces HbA1c when compared with placebo (16768). However, a small meta-analysis including this study shows that taking flaxseed lignans does not reduce fasting blood glucose or HbA1c (111062).
• Hypercholesterolemia. Oral whole and ground flaxseed modestly reduce lipid levels. Details: Most research shows that taking various flaxseed preparations 30-50 grams daily reduces total cholesterol by 5% to 15% and low-density lipoprotein (LDL) cholesterol by 8% to 18%, but does not seem to affect high-density lipoprotein (HDL) cholesterol, when compared with control (6808,10952,22179,26478,65866,101944,101947,101949,108044,108046)(111064). Apolipoprotein A-1 and apolipoprotein B may be reduced by 6% and 7.5%, respectively (10952). A meta-analysis of clinical studies shows reductions in apolipoprotein A and apolipoprotein B following whole flaxseed supplementation (108046). The cholesterol-lowering effect of flaxseed has been shown in various populations, including those with hypercholesterolemia with/or without diabetes, postmenopausal patients, and patients with chronic kidney disease or cardiovascular risk factors (6808,10952,10978,12910,22180,22181,26478,26480,26488,101944)(101949,101950,111064). One large meta-analysis suggests that the most consistent effect occurs in patients with hypercholesterolemia (101947). Another large meta-analysis suggests that patients with hypercholesterolemia and healthy patients with a body mass index greater than 25 kg/m2 may benefit the most from treatment (108044). Most research shows that flaxseed reduces triglyceride levels (101947,108046,111064). However, there are certain preparations, such as partially defatted flaxseed (which lacks alpha-linolenic acid content) or flaxseed incorporated into bread products, which might increase triglyceride levels by up to 26% (6808,26488).
• Hypertension. Daily oral flaxseed consumption, especially for longer than 12 weeks, seems to modestly reduce blood pressure. Details: Meta-analyses of mainly small clinical studies in patients with and without hypertension show that taking flaxseed reduces systolic and diastolic blood pressure by an average of 1.1 to 1.8 and 1.0 to 1.3 mmHg, respectively, when compared with control (96426,111063). The effect of flaxseed lignan is unclear. One meta-analysis shows that flaxseed lignan does not seem to reduce blood pressure when compared with control (96426). However, a more recent meta-analysis shows that taking flaxseed lignan has a small effect on systolic, but not diastolic, blood pressure (111063). The length of supplementation may play a role as studies lasting longer than 12 weeks seemed to lower blood pressure to a slightly greater degree than studies lasting less than 12 weeks (96426). The validity of these findings is limited due to the short duration of treatment, the variation in study size, the inclusion of patients with and without hypertension, and the range of doses used. Some clinical research also shows that taking flaxseed may be beneficial for blood pressure reduction in patients with hypertension (111063). One individual clinical study in adults with hypertension shows that taking flaxseed 10 grams or 30 grams daily affects blood pressure in a dose-dependent manner when compared with placebo. After 12 weeks of treatment, systolic and diastolic blood pressure decreased by 12 mmHg and 6 mmHg, respectively, in the high-dose group, compared with 10 mmHg and 7 mmHg, respectively, in the low-dose group (108043).
• Mastalgia. Oral flaxseed seems to reduce symptoms of cyclic mastalgia. Details: Clinical research in healthy Iranian women with cyclic mastalgia shows that taking flaxseed powder 25 grams daily for 2 months reduces breast pain intensity from moderate to mild and also reduces duration of pain when compared with placebo (96250). Other preliminary clinical research shows that eating a muffin containing ground flaxseed 25 grams daily for 3 months reduces symptoms of severe cyclic mastalgia (16766).
• Obesity. Oral flaxseed and flaxseed mucilage seem to modestly improve weight loss in patients who are obese or overweight. However, flaxseed lignan extract does not seem to be beneficial. Details: A meta-analysis of 45 clinical studies including 2,561 overweight or obese adults shows that flaxseed consumption reduces body weight by 1.8 kg, body mass index (BMI) by 0.6 kg/m2, and waist circumference by 1.2 cm when compared with control in adults. The most benefit is seen in adults with a baseline BMI greater than or equal to 27 (96427). Flaxseed consumption of at least 30 grams daily for durations of at least 12 weeks demonstrated the greatest efficacy (96427,101949). The soluble fiber, flaxseed mucilage, has also been studied. A clinical trial in overweight or obese adults shows that taking oral flaxseed mucilage 1280 or 2560 mg mixed in water twice daily with meals for 12 weeks decreases body weight, waist circumference, and BMI in a dose-dependent manner when compared with placebo. After 12 weeks, a 5 kg and 4 kg weight reduction was observed in the high- and low-dose groups, respectively, compared to a 1 kg reduction in the placebo group (108047). The validity of this finding is limited due to short duration of treatment and lack of follow-up. Conversely, flaxseed lignan extract does not appear to be effective in reducing weight, BMI, or waist circumference (96427). Some research has investigated whether variants in genes related to satiety and appetite play a role in any effect of flaxseed on weight loss and appetite. A small clinical trial in adults with overweight or obesity shows that taking defatted flaxseed flour in biscuits daily for 8 weeks modestly reduces body weight, BMI, triglycerides, or blood glucose only in those with specific gene variants when compared with control biscuits (111066). More information is needed to determine how these gene variants play a role in the connection between nutrition and obesity.
• Systemic lupus erythematosus (SLE) nephritis. Oral flaxseed might be beneficial for improving kidney function in SLE. Details: Some small clinical studies suggest that taking whole or ground flaxseed orally might improve serum creatinine levels in people with SLE nephritis (6802,8021).

POSSIBLY INEFFECTIVE

• Osteoporosis. Oral flaxseed does not seem to be beneficial in osteoporosis. Details: Clinical research shows that consuming ground flaxseed 40 grams daily for up to one year does not affect markers of bone metabolism or improve bone mineral density in healthy, postmenopausal adults (10952,12910). Similarly, taking flaxseed extract 550 mg three times daily for 6 months does not appear to improve bone mineral density when compared with placebo in older adults (21197).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using oral flaxseed for acne, there is insufficient reliable information about the clinical effects of flaxseed for this purpose.
• Benign prostatic hyperplasia (BPH). It is unclear if oral flaxseed lignan improves symptoms of BPH. Details: A small clinical study in patients with BPH shows that taking a specific flaxseed lignan extract (BeneFlax, Archer Daniels Midland Co.) 300 mg or 600 mg daily for 4 months improves lower urinary tract symptom scores when compared with placebo. Additionally, the 600 mg dose was associated with improved quality of life when compared with placebo (21193).
• Breast cancer. It is unclear if oral flaxseed reduces the risk for breast cancer or the progression of breast cancer. Details: A small clinical study in females newly diagnosed with breast cancer shows that consuming a muffin containing ground flaxseed 25 grams daily for about 40 days reduces markers of tumor cell proliferation when compared with baseline, but not when compared with placebo (16765). The effect of flaxseed intake on breast cancer outcomes was not assessed. Dietary lignans, which occur in flaxseed, have been linked with a lower risk of developing breast cancer. Most large-scale population studies have found that high intake of dietary lignans and serum levels of the lignan enterolactone are associated with a reduced risk of developing breast cancer (16775,16776,16777,16779,16781,16782,16783,16785). It is unclear if flaxseed lignan, specifically, is beneficial for reducing the risk of breast cancer.
• Burning mouth syndrome. Flaxseed has only been evaluated in a mouthwash in combination with German chamomile; its effect when used alone is unclear. Details: A small clinical study in female patients with burning mouth syndrome shows that using a homemade mouthwash containing boiled whole flaxseed 10 grams and German chamomile 1 gram in 200 mL of water 3-4 times daily for 3 months decreases subjective burning and dry mouth symptoms, increases salivary flow rate, and decreases saliva viscosity when compared with baseline (104807). However, the validity of these results is limited by the lack of a control group and product standardization, as the mouthwash was prepared by each patient from ingredients they purchased.
• Cardiovascular disease (CVD). It is unclear if oral flaxseed or flaxseed lignans reduce the development or progression of CVD. Details: A small clinical study in older adults that were also given dietary advice shows that taking flaxseed 30 grams daily for 12 weeks, starting 4 weeks after percutaneous coronary intervention (PCI), more than doubles flow mediated dilation when compared with a group not taking flaxseed (101945). However, population research has found that total dietary intake of lignans, including flaxseed lignans, is not associated with a reduced risk of coronary heart disease or all-cause mortality (16787). This research did not specifically assess the effect of flaxseed intake on CVD.
• Chronic kidney disease (CKD). Although there is interest in using oral flaxseed for CKD, there is insufficient reliable information about the clinical effects of flaxseed for this condition.
• Colorectal cancer. It is unclear if oral flaxseed reduces the risk of colorectal cancer. Details: Flaxseed is one source of dietary lignans. Population research has found that serum levels of lignans are not associated with risk of developing colorectal cancer (16778). However, other population research has found that high dietary intake of lignans is associated with a reduced risk of colorectal cancer (16784), and that higher serum levels of dietary lignans are associated with a reduced risk of colorectal adenomas (16788). It is unclear if flaxseed lignan, specifically, is beneficial for reducing the risk of colorectal cancer.
• Endometrial cancer. It is unclear if oral flaxseed reduces the risk of endometrial cancer. Details: Flaxseed is one source of dietary lignans. A large-scale population study has found that serum levels of lignans are not associated with risk of developing endometrial cancer (16786).This research did not specifically assess the effect of flaxseed intake on endometrial cancer risk.
• Fatigue. It is unclear if oral ground flaxseed reduces fatigue in overweight children. Details: A small non-blinded clinical study in overweight healthy children ages 7-18 shows that consuming ground flaxseed 20 grams in divided doses with food daily for 4 weeks seems to modestly reduce mental fatigue but not physical fatigue when compared with puffed wheat 25 grams daily (105473).
• Impaired glucose tolerance (prediabetes). It is unclear if oral flaxseed is beneficial in prediabetes. Details: A small clinical study in adults with prediabetes shows that consuming milled flaxseed 20 grams or 40 grams daily for 12 weeks does not improve glycemic control, but modestly reduces systolic blood pressure, when compared with no intervention (96434).
• Irritable bowel syndrome (IBS). It is unclear if oral flaxseed improves IBS symptoms. Details: A small open-label clinical study in patients with IBS suggests that consuming whole or ground flaxseed 24 grams daily for 4 weeks does not improve quality of life, severity of IBS symptoms, or number of bowel movements when compared with no intervention (21198).
• Lung cancer. It is unclear if oral flaxseed reduces the risk of lung cancer. Details: Observational research has found that consuming a higher amount of dietary phytoestrogens, such as the lignan metabolites and precursors found in flaxseed, is associated with a lower risk of developing lung cancer when compared to those who consume smaller amounts (13190). It is unclear if flaxseed, specifically, is beneficial for reducing the risk of lung cancer.
• Menopausal symptoms. There is contradictory evidence about the effects of flaxseed for reducing menopausal symptoms. Details: Some preliminary clinical research in postmenopausal adults shows that taking either flaxseed meal 90 grams daily or a specific flaxseed extract (Biogalenica, Medicinal Compounding Pharmacy) 1000 mg daily for 6 months reduces menopausal symptoms and the frequency of hot flashes when compared to baseline (21200). Other small clinical studies in postmenopausal adults show that consuming ground flaxseed orally 40 grams daily reduces symptoms of hot flashes by about 35% and night sweats by about 44% when compared to baseline (10978,12910). However, similar reductions have been observed with placebos, such as wheat germ (12910,18224). Higher quality studies of flaxseed used in food products have yielded negative results. One clinical trial in postmenopausal adults shows that taking a specific flaxseed-containing bar (Glambia Nutritionals) providing 7 grams of flaxseed and 410 mg of lignans reduces hot flash frequency by 28% and hot flash scores by 50% when compared to baseline, but not when compared with placebo (18224). In another small clinical study, consuming muffins containing flaxseed 25 grams daily providing 50 mg lignans did not improve hot flashes or measures of quality of life when compared with placebo in a similar patient population (16762). Eating flaxseed-enriched bread providing 25 grams of flaxseed daily for 12 weeks also did not improve menopausal symptoms or reduce the frequency of hot flashes when compared to control (22176).
• Metabolic syndrome. Small studies suggest that oral flaxseed is beneficial for metabolic syndrome. Details: One small clinical study in older adults shows that taking a specific flaxseed lignan extract (BeneFlax, Archer Daniels Midland Co.) 550 mg three times daily for 6 months reduces metabolic syndrome risk scores when compared with placebo in males, but not females (21197). Another small open-label clinical trial in patients with metabolic syndrome suggests that taking flaxseed powder 30 grams daily for 12 weeks modestly reduces the number of people meeting the criteria for metabolic syndrome when compared with no supplementation (105276). However, food containing flaxseed does not seem to be as beneficial. Some clinical research in Asian Americans with metabolic syndrome shows that eating bread containing flaxseed 30 grams daily plus lifestyle counseling for 12 weeks does not improve markers of metabolic syndrome when compared with lifestyle counseling alone (21199).
• Nonalcoholic fatty liver disease (NAFLD). Small clinical studies suggest that oral flaxseed may modestly reduce markers of liver disease progression in patients with NAFLD. Details: A small clinical pilot study in adults with NAFLD shows that taking brown milled flaxseed 30 grams daily for 12 weeks along with lifestyle modification reduces fibrosis by 21% and steatosis by about 15.3%, compared with reductions of 9.7% and 5.5%, respectively, in those following lifestyle modifications alone (96249). A larger follow-up clinical study in patients with NAFLD shows that taking brown milled flaxseed 30 grams daily for 12 weeks in addition to lifestyle modification reduces steatosis by about 28%, compared with a 16% reduction in the lifestyle modification group (105275).
• Osteoarthritis. It is unclear if topical flaxseed is beneficial in patients with osteoarthritis. Details: A small clinical study in patients with hand osteoarthritis who are using routine treatments shows that using a flaxseed poultice compress once daily for 7 days improves pain by 63% and hand function by 66% when compared with a hot compress or no compress in combination with routine treatments. Some of the benefit was maintained for at least a week following treatment (101946).
• Peripheral arterial disease (PAD). It is unclear if oral flaxseed is beneficial in patients with PAD. Details: Clinical research in patients with PAD shows that taking milled flaxseed 30 grams daily mixed with a variety of foods for one year does not reduce the incidence of cardiac arrhythmias or improve the distance walked until claudication when compared with placebo (101942). This study may have been inadequately powered to detect differences between groups.
• Pharyngitis. Although there is interest in using oral flaxseed for pharyngitis, there is insufficient reliable information about the clinical effects of flaxseed for this purpose.
• Polycystic ovary syndrome (PCOS). It is unclear if oral flaxseed is beneficial in patients with PCOS. Details: A small open-label clinical study in patients with PCOS shows that taking flaxseed 30 grams daily for 12 weeks in conjunction with receiving lifestyle modification advice reduces triglyceride and insulin levels and improves insulin resistance when compared with lifestyle modification advice alone. About 69% of those in the treatment group who had irregular menstrual cycles at baseline had a regular cycle at the end of treatment, compared with no significant improvement in the control group. Flaxseed did not affect body weight, low-density lipoprotein (LDL) cholesterol, or blood glucose when compared with control (101943).
• Prostate cancer. Small clinical studies suggest that oral flaxseed may modestly improve biomarkers of prostate cancer. Details: A very small clinical trial in patients with prostatic intraepithelial neoplasia (PIN), a precancerous proliferation of prostatic epithelial cells, shows that adding ground flaxseed (Alena, Enreco) 30 grams daily to a fat-restricted diet for 6 months lowers prostate specific antigen (PSA) levels and slows prostate epithelium proliferation when compared with baseline (12908). This finding is limited by the lack of a placebo group. A clinical study in patients with prostate cancer awaiting prostatectomy shows that taking ground flaxseed (Alena, Enreco) 30 grams daily with or without a fat-restricted diet for about 30 days reduces tissue proliferation rate, but does not reduce PSA, when compared with control (16761).
• Radiation-induced pneumonitis. It is unclear if oral flaxseed is beneficial for preventing radiation-induced pneumonitis in patients with non-small cell lung cancer (NSCLC). Details: A very small, clinical trial in adults with locally advanced or metastatic NSCLC currently undergoing chemoradiation therapy shows that taking ground flaxseed (Golden Valley Flax; Hylden Farms) 40 grams daily, starting one week prior to radiotherapy and continuing until completion of treatment, may reduce the risk of radiation-induced pneumonitis when compared with baseline, with only 1 patient (5%) developing a grade ≥3 event and no cases of grade 2 events (108042). The validity of these findings is limited by the lack of a comparator group and a low adherence rate due to tolerability issues.
• Rheumatoid arthritis (RA). It is unclear if oral flaxseed is beneficial in patents with RA. Details: A clinical study in adults with RA shows that following either a regular or anti-inflammatory diet supplemented with oral flaxseed 30 grams daily for 12 weeks improves disease activity score 28-joint (DAS28-ESR), as well as pain and quality of life outcomes, such as emotional well-being and vitality, when compared with baseline (108048). The validity of these findings is limited by the lack of a comparator group.
• Ulcerative colitis. It is unclear if oral flaxseed is beneficial in patients with ulcerative colitis. Details: A small open-label clinical study in patients with ulcerative colitis shows that taking ground flaxseed 30 grams daily for 12 weeks seems to modestly reduce inflammatory markers and disease severity and improve quality of life when compared with control (101941). A nonblinded, clinical study in adults with mild to moderate ulcerative colitis shows that taking brown milled flaxseed 15 grams twice daily for 12 weeks improves disease severity scores when compared with placebo (108045). The validity of these findings is limited by the lack of blinding and short duration of treatment. More evidence is needed to rate flaxseed for these uses.

(Read more about FLAXSEED)

POSSIBLY EFFECTIVE

• Benign prostatic hyperplasia (BPH). Taking oral pumpkin seed or pumpkin seed oil may improve symptoms of BPH. Details: One study in patients with BPH shows that taking pumpkin seed 5 grams twice daily for 12 months may be more effective for controlling symptoms than pumpkin seed extract 1000 mg twice daily (92383). A specific pumpkin seed extract (Prosta Pink Forte) 1-2 capsules daily for 12 weeks has also been used (11231). Some preliminary clinical research also suggests that taking pumpkin seed oil (Prostafit, EuRho Vital) two tablets daily for 6 months may be as effective as the medication prazosin (92382). Pumpkin seed oil has also been compared with tamsulosin. A clinical study comparing pumpkin seed oil 360 mg twice daily to tamsulosin 0.4 mg once nightly for 3 months shows that both treatment groups report improvements in BPH symptoms and quality of life when compared with baseline, although improvement appears greater in the tamsulosin group, specifically when measured at 1 month and 3 months. In the pumpkin seed oil group, adverse effects were reported in 0% of patients, compared with 15% of patients taking tamsulosin (107842). The validity of this study is limited due to the short duration of treatment. Pumpkin seed oil or extracts have also been studied in combination with saw palmetto (6777), with saw palmetto, nettle root, and lemon extracts plus beta carotene (5093), and with saw palmetto, small flowered willow herb, lycopene, and pygeum (92379).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. Oral pumpkin seed oil might improve hair regrowth in males with mild to moderate hair loss. Details: Clinical research in males with mild to moderate hair loss shows that taking pumpkin seed oil (Octa Sabal Plus, Dreamplus Co. Ltd.) 400 mg daily in divided doses for 24 weeks increases hair count by 30% when compared with placebo. Self-rated improvement and satisfaction scores were 62% and 52% with pumpkin seed oil and placebo, respectively (92378). Clinical research in patients with female pattern hair loss shows that applying 1 mL of pumpkin seed oil to the scalp daily for 30 days improves hair regrowth similarly to minoxidil 5% foam, 1 mL daily (104974).
• Interstitial cystitis. Although there is interest in using oral pumpkin for interstitial cystitis, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Intestinal parasite infection. Although there is interest in using oral pumpkin for intestinal parasite infection, there is insufficient reliable information about the clinical effects of pumpkin for this condition.
• Overactive bladder. Oral pumpkin seed oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with overactive bladder shows that taking a specific combination product (Granu Fink femina, Omega Pharma) containing pumpkin seed oil 227 mg, sweet sumac bark extract 56 mg, and hops cone extract 18 mg three times daily for 12 weeks decreases the frequency of urination and leakage and improves quality of life when compared to baseline (103253). The validity of these findings is limited by the lack of a control group. Additionally, it is unclear if these findings are due to pumpkin seed oil, other ingredients, or the combination.
• Urinary tract infections (UTIs). Although there is interest in using oral pumpkin for UTIs, there is insufficient reliable information about the clinical effects of pumpkin for this condition. More evidence is needed to rate pumpkin for these uses.

(Read more about PUMPKIN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Obesity. Preliminary clinical research in healthy overweight males shows that consuming a bread providing quinoa flour 20 grams daily for 4 weeks does not affect anthropometric measures, blood pressure, or plasma levels of glucose or cholesterol when compared with consuming a refined wheat bread (99147).
• Postmenopausal conditions. One small clinical study in postmenopausal adults shows that consuming quinoa flakes 25 grams daily for 4 weeks does not improve glycemic or lipid indices or anthropometric measures when compared with consuming corn flakes (99148). More evidence is needed to rate quinoa for these uses.

(Read more about QUINOA)

POSSIBLY EFFECTIVE

• Hypertension. Oral sesame oil seems to reduce blood pressure by a small amount. Details: Meta-analyses of clinical research involving patients with or without hypertension show that taking sesame, or the sesame constituent sesamin, can reduce both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (96179,108355,108357). One meta-analysis of eight clinical studies shows that sesame or sesamin can reduce SBP by 8 mmHg and DBP by 6 mmHg when compared with control. In a subgroup analysis of patients with hypertension, reductions in SBP and DBP were 11 mmHg and 9 mmHg, respectively. In a subgroup analysis by formulation, sesame oil was shown to reduce SBP and DBP by 13 mmHg and 10 mmHg, respectively, while whole sesame seed, ground seed, or sesame supplement lowered SBP by only 3 mmHg and did not lower DBP (96179). Another meta-analysis of clinical studies involving patients with hypertension, metabolic syndrome, or kidney failure shows that taking sesame oil reduces SBP and DBP by 3 mmHg and 2 mmHg, respectively, although benefits were limited to studies of less than 8 weeks (108355). Some research on sesame oil involved replacing other cooking oils with a specific brand of sesame oil (Idhayam Gingelly oil, V.V.V. & Sons) 35 grams daily for about 6-9 weeks. Patients included in these studies were also using atenolol, nifedipine, and/or hydrochlorothiazide as antihypertensives (27652,27654,27655). Other preliminary clinical research shows that using a 20:80 blend of sesame oil and rice bran oil (Vivo, Adani Wilmar) as cooking oil for 8 weeks improves blood pressure and lipid profile in patients with hypertension. In patients using nifedipine, using the oil blend seems to reduce systolic and diastolic blood pressure by an additional 2 to 2.2-fold over nifedipine alone (96180).

POSSIBLY INEFFECTIVE

• Cough. Oral sesame oil does not seem to be beneficial for cough in children. Details: Clinical research in children with an acute cough due to common cold shows that taking sesame oil 5 mL by mouth at bedtime for 3 consecutive days does not reduce cough strength or cough frequency when compared with placebo (27647).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Although there is interest in using topical sesame oil for aging skin, there is insufficient reliable information about the clinical effects of sesame for this purpose.
• Alzheimer disease. Although there is interest in using oral sesame for Alzheimer disease, there is insufficient reliable information about the clinical effects of sesame for this condition.
• Anemia of chronic disease. Although there is interest in using oral sesame for anemia of chronic disease, there is insufficient reliable information about the clinical effects of sesame for this condition.
• Anxiety. Although there is interest in using topical sesame oil for anxiety, there is insufficient reliable information about the clinical effects of sesame for this purpose.
• Bowel obstruction. It is unclear if oral sesame oil is beneficial for bowel obstruction. Details: Preliminary clinical research in adults with adhesive small bowel obstruction shows that giving sesame oil 150 mL through a nasogastric tube along with standard treatment reduces the need for surgical intervention when compared with standard treatment alone. Also, the resolution time of the obstruction was 6 hours faster and the duration of hospitalization was 4 days shorter for patients treated with sesame oil plus standard treatment when compared with standard treatment alone (27645). Standard treatment consisted of stopping oral intake of food, performing nasogastric tube decompression, administering intravenous fluids with electrolytes, and providing parenteral antibiotics if leukocytosis was present.
• Burns. It is unclear if topical sesame oil is beneficial for burns. Details: Preliminary clinical research in adults and children with partial thickness thermal burns covering less than 40% of body surface area shows that topical application with a moist exposed burn ointment (MEBO) containing sesame oil, beta-sitosterol, berberine, and other unspecified plant ingredients every 4 hours reduces the median time to 75% healing by 3 days (17 days vs. 20 days) and improves analgesic effects during the first 5 days of treatment when compared with a control group receiving cleansing with chlorhexidine 0.05%. The MEBO was left on the burn for 5 days, followed by removal and reapplication at 4 hourly intervals on day 5, to be left on until day 14 (13526).
• Cardiovascular disease (CVD). Although there is interest in using oral sesame for CVD, there is insufficient reliable information about the clinical effects of sesame for this condition.
• Cataracts. Although there is interest in using oral sesame for cataracts, there is insufficient reliable information about the clinical effects of sesame for this condition.
• Chemotherapy-induced phlebitis. It is unclear if massage with topical sesame oil is beneficial for chemotherapy-induced phlebitis. Details: Preliminary clinical research in patients with colorectal cancer and chemotherapy-induced phlebitis shows that applying 10 drops of sesame oil within a 10 cm radius of the affected veins as part of a 5-minute, twice-daily massage reduces pain after 7 days when compared with massage alone (103227).
• Child growth. It is unclear if massage with topical sesame oil is beneficial for child growth. Details: Preliminary clinical research in full-term healthy infants shows that administering a daily massage with sesame oil 20 mL for 4 weeks improves infant length by 1 cm, midarm circumference by 0.9 cm, and midleg circumference by 0.7 cm when compared with a control group that did not receive a massage (29722). It is unclear if these effects are due to sesame oil, massage, or the combination.
• Cognitive impairment. It is unclear if oral sesame is beneficial for cognitive impairment. Details: Clinical research in older adults with memory impairment shows that taking sesame oil cake extract (Keukdong H-Pharm Co., Ltd.) 500 mg three times daily for 12 weeks modestly improves some, but not all, measures of cognitive function when compared with placebo (108351). In addition, preliminary clinical research in patients with mild cognitive impairment shows that taking two capsules of a combination product containing the sesame constituent sesamin 5 mg and astaxanthin 3 mg daily for 12 weeks increases psychomotor and processing speed when compared with placebo. However, there was no effect on memory, attention, or overall severity of cognitive symptoms (99863). It is not clear if these effects are due to sesamin, astaxanthin, or the combination.
• Dental plaque. It is unclear if rinsing the mouth with sesame oil or pulling the oil through the teeth is beneficial for dental plaque. Details: Preliminary clinical research in children 12-14 years of age shows that rinsing with 10 mL of ozonated or non-ozonated sesame oil for 10 minutes daily for 15 days reduces plaque when compared with baseline. The ozonated sesame oil was superior to non-ozonated sesame oil, showing a similar improvement in plaque when compared with chlorhexidine mouthwash (103226). A small clinical study in healthy adults shows that pulling sesame oil 10 mL through the teeth for 15-20 minutes twice daily for 4 days has similar effects on full-mouth prevention of plaque regrowth, tooth staining, gingival index, and bleeding when compared with pulling coconut oil through the teeth (106038).
• Diabetes. It is unclear if oral sesame oil is beneficial for diabetes. Details: Meta-analyses suggest that taking sesame for 6-12 weeks modestly reduces levels of fasting blood glucose and glycated hemoglobin (HbA1c), but not insulin levels or insulin resistance, when compared with placebo, baseline, or other control. Sesame oil and seed flour, tahini, and sesamin were used in the included research (108350,108352,108355). Although most studies included in these meta-analyses were conducted in patients with type 2 diabetes, one study (103231) was conducted in patients with metabolic syndrome. One small clinical trial included in these meta-analyses shows that replacing other cooking oils with a specific brand of sesame oil (Idhayam Gingelly oil, V.V.V. & Sons) 35 grams daily for 45 days reduces blood glucose levels and HbA1c when compared with baseline in patients with diabetes who are also using glibenclamide (27654). Sesame oil has also been investigated in combination with rice bran oil. One preliminary clinical trial in patients with type 2 diabetes not using antidiabetes medications shows that using a specific 20:80 blend of sesame oil and rice bran oil (Vivo, Adani Wilmar) as the only cooking oil for 8 weeks reduces levels of fasting blood glucose by 14% and reduces HbA1c when compared with baseline. In patients taking glibenclamide 5 mg daily, using this oil blend reduces fasting blood glucose and HbA1c when compared with glibenclamide alone (96177). The use of sesame oil has also been investigated for improving cardiometabolic markers in patients with type 2 diabetes. Clinical research in adults taking antidiabetes medications shows that replacing regular dietary oils with sesame oil or a blend of sesame and canola oils for 9 weeks does not improve most cardiometabolic markers when compared with canola oil or sunflower oil as a control (108353).
• Gastric cancer. Although there is interest in using oral sesame for gastric cancer prevention, there is insufficient reliable information about the clinical effects of sesame for this purpose.
• Gingivitis. It is unclear if pulling sesame oil through the teeth is beneficial for gingivitis. Details: Preliminary clinical research in adolescent males with plaque-induced gingivitis shows that oil pulling with sesame oil for one minute daily each morning prior to brushing for 10 days reduces dental plaque and gingivitis when compared with baseline (27648). The validity of this finding is limited by the lack of a comparator group.
• Hemorrhoids. Topical sesame oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in adults with symptomatic mild to moderate (first- and second-degree) internal hemorrhoids shows that application of a cream containing sesame oil and aqueous extracts of guggul and Allium ampeloprasum as a thin layer to the anus twice daily for 3 weeks improves anal irritation and itching, bleeding, pain, defecation discomfort, and swelling sense when compared with baseline. In contrast, patients using a placebo cream experienced an improvement only in anal itching (105751). The poor study methodology and lack of statistical comparison to the placebo group limit the validity of these findings.
• HIV/AIDS-related wasting. Oral sesame has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with HIV shows that consuming 300 grams of a chickpea and sesame-based food supplement daily for 3 months, along with routine sulfamethoxazole-trimethoprim, improves weight gain, body mass index, and mid-upper arm circumference in 73% of patients, and results in improved physical performance in 78% of patients, when compared to baseline (27657). The validity of these findings is limited by the lack of a comparator group.
• Hyperlipidemia. It is unclear if oral sesame is beneficial for hyperlipidemia. Details: A meta-analysis of a limited number of clinical studies that included mainly patients without hyperlipidemia shows that consuming sesame 25-50 grams daily or using sesame oil 3.5-35 grams daily for up to 10 weeks does not reduce levels of total or low-density lipoprotein (LDL) cholesterol when compared with baseline (96181). However, a more recent meta-analysis with similar studies shows that consuming sesame reduces levels of total cholesterol by 16 mg/dL, although there is no effect on levels of LDL cholesterol or high-density lipoprotein (HDL) cholesterol (108357). Both analyses show that taking sesame reduces triglyceride levels by about 21 mg/dL (96181,108357). Significant heterogeneity of the included studies and patient populations limits the validity of these results.
• Insect repellent. Although there is interest in using topical sesame oil as an insect repellent, there is insufficient reliable information about the clinical effects of sesame for this purpose.
• Male infertility. It is unclear if oral sesame is beneficial for male infertility. Details: Preliminary clinical research in males with infertility shows that taking sesame 0.5 mg/kg daily for 3 months modestly improves sperm count and motility, but not sperm morphology, when compared with baseline (108356). The validity of these findings is limited by the lack of a comparator group.
• Menopausal symptoms. Although there is interest in using oral sesame for menopausal symptoms, there is insufficient reliable information about the clinical effects of sesame for this purpose.
• Metabolic syndrome. It is unclear if oral sesame oil is beneficial for improving metabolic parameters in adults with metabolic syndrome. Details: Preliminary clinical research in patients with metabolic syndrome shows that taking sesame oil 30 mL with or without vitamin E 400 mg daily for 8 weeks improves levels of fasting blood glucose, lipids, and blood pressure when compared with sunflower oil. In those taking sesame oil alone, total cholesterol and triglycerides were reduced by about 13 mg/dL, while low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were not affected. In those also taking sesame oil with vitamin E, total cholesterol and triglycerides were reduced by 17 mg/dL and 21 mg/dL, respectively, while HDL cholesterol was increased by 4 mg/dL. Additionally, systolic and diastolic blood pressure were reduced by 10 mmHg and 8 mmHg, respectively, in those taking sesame oil alone, versus 15 mmHg and 9 mmHg, respectively, in those taking sesame oil with vitamin E (103231).
• Miscarriage. It is unclear if oral sesame is beneficial for the management of an incomplete miscarriage. Details: Preliminary clinical research in patients with incomplete abortion related to miscarriage shows that taking sesame seed twice daily for 5 days results in complete resolution of retained products of conception in 84% of individuals, based on a sonographic assessment, compared with 26% of those receiving expectant management as control. There was also a 2-day reduction in the duration of vaginal bleeding when compared with control. Each dose of ground sesame seed powder 30 grams was boiled in 200 mL water for 4 minutes and then filtered before drinking (108346).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral sesame oil is beneficial for NAFLD. Details: Clinical research in females with NAFLD shows that taking sesame oil 30 grams daily for 12 weeks reduces the severity of fatty liver in 89% of patients taking sesame oil, compared with 58% of those taking sunflower oil. There were also modest reductions in levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), but not alkaline phosphatase (ALP), when compared with sunflower oil. All patients were also consuming a 500-kcal hypocaloric diet (108354).
• Obesity. It is unclear if oral sesame is beneficial for weight loss. Details: Meta-analyses of clinical research show that taking sesame or sesame oil in doses of at least 35 grams daily reduces body weight by up to 2 kg and body mass index by up to 1 kg/m² when compared with no oil or a control oil. Clinical studies included in these meta-analysis enrolled patients with type 2 diabetes, hypertension, hypercholesterolemia, and others, and were not limited to overweight or obese individuals (108355,108357). A small clinical study in overweight individuals shows that replacing regular dietary oil with sesame oil for 9 weeks does not improve levels of most cardiometabolic risk factors, although there were modest beneficial effects on insulin (108349).
• Osteoarthritis. It is unclear if topical sesame oil is beneficial for knee osteoarthritis. Details: Preliminary clinical research in patients with osteoarthritis of the knee shows that applying sesame oil 1.5 mL to the affected knee three times daily for 4 weeks reduces pain and improves physical function when compared to baseline. These improvements were similar to those seen in patients applying diclofenac topical gel (103228).
• Osteoporosis. Although there is interest in using oral sesame for osteoporosis, there is insufficient reliable information about the clinical effects of sesame for this condition.
• Pain (acute). It is unclear if massage with topical sesame oil is beneficial for acute pain caused by blunt trauma. Details: One small clinical study shows that using a specific sesame oil (Saman sesame oil, Saman sesame oil Co.) topically as part of a light massage for 5 minutes twice daily for 9 days moderately reduces acute pain caused by blunt trauma to an extremity by day 6 when compared with a light massage with placebo oil. However, the sesame oil massage does not reduce the use of nonsteroidal anti-inflammatory drugs when compared with placebo oil (96178). A similar clinical study in the same population shows that using sesame oil extracted from tahini topically as part of a light massage for 5 minutes 3 times a day for 2 days improves pain severity, pain sensitivity, and heaviness of the painful site by about 20% when compared with baseline (106034). The lack of statistical comparison to the placebo group limits the validity of these findings.
• Peptic ulcers. Although there is interest in using oral sesame for peptic ulcers, there is insufficient reliable information about the clinical effects of sesame for this purpose.
• Rheumatoid arthritis (RA). It is unclear if oral sesame is beneficial for RA. Details: Preliminary clinical research in females with RA shows that taking the sesame constituent sesamin (Sesamin, Scivation, Inc.) 200 mg daily for 6 weeks improves physical function and reduces pain, the number of tender and swollen joints, and markers of inflammation such as C-reactive protein when compared with placebo (103230).
• Stroke. Although there is interest in using oral sesame for stroke, there is insufficient reliable information about the clinical effects of sesame for this purpose. More evidence is needed to rate sesame for these uses.

(Read more about SESAME)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• HIV/AIDS. Preliminary clinical research in HIV patients using antiretroviral therapy shows that taking a specific product containing sorghum extract and other ingredients (Jobelyn, Health Forever Product Ltd.) orally twice daily for 12 weeks improves CD4+ T cell count when compared with antiretroviral therapy alone. Hemoglobin levels were increased compared with baseline in patients ineligible for antiretrovirals (97674).
• Iron deficiency anemia. Preliminary clinical research shows that taking a specific product containing sorghum extract and other ingredients (Jobelyn, Health Forever Product Ltd.) orally once daily for 3 weeks does not improve red blood cell indices in patients with anemia who were also taking iron 600 mg daily and folic acid 5 mg daily (97675).
• Obesity. Preliminary clinical research in overweight and obese men shows that eating extruded sorghum cereal 40 grams each morning along with a calorie restricted diet for 8 weeks reduces body fat by around 2%, but does not appear to improve body weight, body mass index, or waist circumference, when compared with extruded wheat cereal plus calorie restriction (103898). More evidence is needed to sorghum for these uses.

(Read more about SORGHUM)

POSSIBLY EFFECTIVE

• Coronary heart disease (CHD). The U.S. Food and Drug Administration (FDA) allows a qualified health claim stating that using high-oleic acid sunflower oil as a replacement for other dietary fats and oils higher in saturated fat may reduce the risk of CHD. Details: A meta-analysis of clinical studies shows that replacing 7.5% of energy from partially hydrogenated vegetable oils with high-oleic acid sunflower oil can reduce CHD risk by about 9% to 19%. Furthermore, analysis of results from observational studies found that replacing partially hydrogenated oil with high-oleic acid sunflower oil is associated with a 16% to 35% reduction in the risk of CHD events (95745). The FDA allows for a qualified health claim that replacing dietary fats and oils higher in saturated fat with high-oleic acid sunflower oil may reduce the risk of CHD. To achieve this benefit, the use of high-oleic acid sunflower oil should not increase total daily energy intake. The suggested daily dietary intake is about 20 grams (1.5 tbsp) of high-oleic sunflower oil in place of other fats and oils (98563). Sunflower oil that contains high amounts of linoleic acid rather than oleic acid does not appear to improve cholesterol levels or reduce the risk of cardiovascular events in patients with CHD (96205).
• Hypercholesterolemia. Consuming sunflower oil in the diet may reduce low-density lipoprotein (LDL) cholesterol levels in some patients. Details: There is evidence that using sunflower oil in the diet as 45-50 grams daily for up to 12 weeks is more effective than olive oil for decreasing LDL cholesterol and apolipoprotein B levels in healthy individuals (9780). Also, clinical research in patients with mild hyperlipidemia or moderate hypercholesterolemia shows that consuming specific brands of mid-oleic acid (NuSun) or high-oleic acid (Sunola, Meadow Lea Foods) sunflower oils as 15% to 20% of dietary calories for up to 5 weeks is more effective than olive oil or saturated fat for decreasing total cholesterol, LDL cholesterol, and apolipoprotein B levels (76697,76698). Also, consuming a high-oleic sunflower oil-rich diet for 3 weeks decreases total cholesterol levels to a greater extent than diets enriched with palm oil or medium-chain triglycerides in patients with mild hypercholesterolemia (67569). Other preliminary clinical research in patients with moderate hypercholesterolemia shows that consuming a diet rich in sunflower oil for 3 weeks decreases total cholesterol and LDL cholesterol levels when compared with baseline. However, levels of high-density lipoprotein (HDL) cholesterol appear to be lowered as well (76714). Despite these beneficial effects, sunflower oil might be less effective than some other dietary oils. Taking sunflower oil for 3 months appears to be less effective than rice bran oil for lowering cholesterol in patients with hypercholesterolemia (76699). Also, while consuming sunflower oil 45 grams daily, as part of the diet and as a supplement, for 12 weeks reduces levels of total cholesterol and LDL cholesterol when compared to baseline, it appears to be less effective at reducing total cholesterol levels than flaxseed oil in certain patients at risk for atherosclerosis (76696). In addition, taking sunflower oil 15.1 grams daily for 4 months does not appear to reduce levels of total or LDL cholesterol in patients with peripheral vascular disease (76691).

POSSIBLY INEFFECTIVE

• Hypertension. Oral sunflower oil does not seem to lower blood pressure. Details: Preliminary clinical research in adults with hypertension shows that taking sunflower oil 30-40 grams daily for one year is less effective than extra-virgin olive oil for reducing blood pressure (5091). Also, clinical research in elderly adults with hypertension shows that taking 60 grams of sunflower oil daily for 4 weeks is less effective than virgin olive oil for reducing systolic blood pressure (76692).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. It is unclear if oral sunflower oil is beneficial for atherosclerosis; some clinical research suggests that it may provide less benefit than other dietary oils. Details: Some preliminary clinical research in individuals with overweight and obesity shows that taking sunflower oil 30 mL (about 27 grams) daily for 90 days decreases carotid intima-media thickness (CIMT) by 3.5% when compared to baseline, but not when compared with olive oil or flaxseed oil. Sunflower oil also improves flow-mediated vasodilation by 73% when compared to baseline, compared with no improvement in those taking flaxseed oil or olive oil (99303). Other preliminary clinical research in individuals waiting for carotid endarterectomy shows that taking sunflower oil 6 grams daily for up to 189 days is less effective than the same dose of fish oil, and equivalent to control oil, for improving the status of atherosclerotic plaques (76688).
• Atopic dermatitis (eczema). Although there is interest in using topical sunflower oil for atopic dermatitis, there is insufficient reliable information about the clinical effects of sunflower oil for this condition.
• Child growth. It is unclear if topical sunflower oil is beneficial for early child growth. Details: A large preliminary clinical trial in newborn infants in India shows that exclusive topical application of 10 mL of high-linoleic acid sunflower oil, an average of 2.7 times daily for about one month, increases weight gain by 1.3 gram/kg daily when compared with a control group exclusively given traditional vigorous massage with mustard oil an average of 2.4 times daily. The increase in weight gain was highest for infants weighing less than 1500-2000 grams at birth (108141). However, it is unclear if any beneficial effects are due to the sunflower oil, the massage, their combination, or the lack of mustard oil.
• Dry mouth. It is unclear if rinsing the mouth with sunflower oil is beneficial for dry mouth. Details: Preliminary clinical research in adults with moderate dry mouth associated with medication use shows that using a sunflower oil mouth rinse and gargling for 5-8 minutes before spitting it out twice daily for 7 days improves dry mouth scores by 23% when compared to baseline. Sunflower oil also improves the ability to swallow and sleep with dry mouth, but not other dry mouth symptoms or saliva flow rate, when compared with control (105523). This study may have been inadequately powered to detect a difference between groups.
• Dry skin. It is unclear if topical sunflower oil is beneficial for dry skin in infants. Details: Preliminary clinical research in full-term, newborn infants shows that topical application of 4 drops of sunflower oil to each of three parts of the body twice daily for 4 weeks improves skin hydration, but not skin barrier function or the presence of redness or rash, when compared with not using topical oil. Furthermore, use of sunflower oil may impede the normal development of skin barrier function that occurs during the first four weeks of life (96144).
• Fetal and premature infant mortality. It is unclear if topical sunflower oil is beneficial for preventing early mortality in premature infants. Details: A large clinical trial in newborn infants in India shows that exclusive topical application of 10 mL of high-linoleic acid sunflower oil, an average of 2.7 times daily for about one month, reduces infant mortality by 58% when compared to a control group exclusively given traditional vigorous massage with mustard oil an average of 2.4 times daily. A subgroup analysis of premature infants also shows a 52% reduction in mortality with the use of high-linoleic acid sunflower oil when compared with control (108143). However, it is unclear if any beneficial effects are due to the sunflower oil, the massage, their combination, or the lack of mustard oil.
• Prematurity. Small to moderate-sized clinical studies suggest that topical sunflower oil might increase body weight, reduce length of hospital stay, and improve skin hydration and skin integrity in preterm neonates. Details: Preliminary clinical research in preterm infants with low birth weight shows that massaging for 5-10 minutes using sunflower oil 10 mL/kg three times daily for 2 weeks increases weight gain by approximately 35% over 2 months when compared with massage using no oil. Sunflower oil massage does not appear to increase length or head circumference (96145). A small clinical study in premature infants in the intensive care unit (ICU) shows that a similar massage with sunflower oil three times daily for 5 days shortens ICU stay by about 5 days when compared with no massage. Furthermore, over the ICU stay, infants in the sunflower oil massage group gained an average of 15 grams, whereas infants in the control group experienced weight loss (98479). The effect of sunflower oil on skin hydration and integrity in preterm infants has also been assessed. A clinical trial of 90 preterm infants in a Turkish neonatal ICU shows that whole body skin treatment (not massage) with either sunflower oil or almond oil 4 mL/kg four times daily for 5 days improves measures of skin hydration and skin integrity when compared with control infants that did not receive oil treatment. The sunflower and almond oil treatments are equally effective (105524). Another clinical study in 90 infants (42% preterm) in a Turkish neonatal ICU shows that whole body skin treatment (not massage) with sunflower oil or liquid Vaseline 3-4 mL for preterm and 5-6 mL for full-term infants daily for 16 days improves measures of skin integrity when compared with control infants that did not receive any oil treatment. Skin integrity scores were better in the sunflower oil group than liquid Vaseline at some time points (111726).
• Psoriasis. Although there is interest in using topical sunflower oil for psoriasis, there is insufficient reliable information about the clinical effects of sunflower oil for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using oral sunflower oil for RA, there is insufficient reliable information about the clinical effects of sunflower oil for this condition.
• Tinea pedis. It is unclear if topical sunflower oil is beneficial for tinea pedis. Details: Preliminary clinical research shows that topical application of a specific brand of ozonized sunflower oil (Oleozon) twice daily for 6 weeks is as effective as ketoconazole for curing athlete's foot (76687). More evidence is needed to rate sunflower oil for these uses.

(Read more about SUNFLOWER OIL)

EFFECTIVE

• Imerslund-Grasbeck disease. Intramuscular vitamin B12 is effective for patients with this condition. Details: Administering intramuscular vitamin B12 (hydroxocobalamin) 1 mg daily for 10 days, followed by monthly injections for the remainder of a patient's life, is effective for treating familial selective vitamin B12 malabsorption (Imerslund-Grasbeck disease) (15,82862).
• Vitamin B12 deficiency. Administering vitamin B12 orally, intramuscularly, or intranasally is effective for preventing and treating vitamin B12 deficiency. Details: Vitamin B12 deficiency has varying definitions but is often defined as vitamin B12 (cobalamin) levels less than 180-200 pmol/L (or 240 pg/mL). Some believe that only intramuscular vitamin B12 is effective for treating vitamin B12 deficiency. However, clinical research shows that oral therapy increases cobalamin levels similarly to intramuscular administration, even in patients with pernicious anemia or malabsorption, if a high enough dose is given (2909,2911,2915,9335,82832) (82836,82949,82860,103976,103972,107141,107144). Some evidence suggests that the most effective oral dose is between 647-1032 mcg daily (13106). However, in certain situations, intramuscular treatment might be more appropriate. Guidelines by the British Committee for Standards in Hematology recommend only intramuscular vitamin B12 for initial treatment of severe vitamin B12 deficiency in patients with pernicious anemia, malabsorption disorders, or neurological involvement (94722). Intramuscular vitamin B12 is also appropriate in patients with diarrhea or vomiting and those likely to be nonadherent (103972). Vitamin B12 deficiency is especially common in older adults, primarily due to lack of intrinsic factor and malabsorption (2915,2919,9335). Daily supplementation with vitamin B12 50-100 mcg might be needed to correct deficiency (10126), while daily doses of 25-37.5 mcg help to maintain normal levels over time (9335). In addition to supplements, foods such as milk and bread fortified with vitamin B12 can be used and are approximately 55% to 60% absorbed by people over 60 years of age (10124). Vitamin B12 deficiency is also common in patients that have had gastric surgery, including gastrectomy and bariatric surgery (107144,107145). Taking vitamin B12 in the doses found in multivitamins or generic vitamin B supplements does not seem to prevent vitamin B12 deficiency following bariatric surgery (107145). However, taking methylcobalamin 500 mcg daily is beneficial for treating vitamin B12 deficiency associated with a total gastrectomy and taking cyanocobalamin 5000 mcg daily is beneficial for preventing vitamin B12 deficiency following gastric bypass (107144). Other people at risk for vitamin B12 deficiency include strict vegetarians who eat no animal products (vegans) and people with increased vitamin B12 requirements associated with pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, and hepatic and kidney disease. Moderate consumption of animal products may not be sufficient to restore and maintain vitamin B12 levels, especially in adolescents who had consumed macrobiotic (vegan type) diets for the first 6 years of life. High dietary intake of vitamin B12 or supplements is usually needed in order to restore and maintain optimal vitamin B12 levels in these adolescents (10125).

LIKELY EFFECTIVE

• Cyanide poisoning. Intravenous hydroxocobalamin (Cyanokit) is likely effective as an antidote for patients with suspected or known cyanide toxicity due to inhalation, ingestion, or skin exposure. Details: Treatment of cyanide poisoning with hydroxocobalamin (Cyanokit) up to 10 grams has been approved by the US Food and Drug Administration (FDA) and recommended by the Australian Resuscitation Council (82870,82905,82906). Hydroxocobalamin is also FDA-approved for treating cyanide toxicity during pregnancy (82904).

POSSIBLY EFFECTIVE

• Canker sores. Sublingual or topical vitamin B12 seems to reduce canker sore symptoms. Details: Clinical research in patients with canker sores shows that applying a topical ointment containing vitamin B12 500 mcg in four divided doses daily for 2 days reduces pain levels by 80% when compared with a control ointment not containing vitamin B12 (96176). Other preliminary clinical research shows that taking vitamin B12 1000 mcg sublingually daily for 6 months reduces the duration of canker sore outbreaks, the number of ulcers, and level of pain when compared with placebo in patients with normal vitamin B12 levels (17242).
• Hyperhomocysteinemia. Oral vitamin B12 in combination with folic acid, and sometimes with vitamin B6, reduces homocysteine levels. Details: While folic acid 0.5-5 mg daily lowers fasting homocysteine levels by an average of 25%, adding vitamin B12 0.5 mg daily produces an additional decrease of about 7% on average (6883,9400,9401,9405,9409,50145,107136). Vitamin B12 in combination with folic acid and other vitamins also reduces homocysteine levels in patients with kidney failure, sickle cell disease, and those receiving nitrous oxide general anesthesia (1489,6883,6884,7289,7881,9324,9414,9415,9416,9481,82941). Some researchers recommend routine use of vitamin B12 with homocysteine-lowering regimens to avoid the risk of neuropathy in people with undetected vitamin B12 deficiency (9405). Using vitamin B12 alone has a limited effect on homocysteine levels, and probably only in those people with vitamin B12 deficiency (2147,9410,9512). Hyperhomocysteinemia is considered by some to be an independent risk factor for atherosclerosis, recurrent thromboembolism, deep vein thrombosis, myocardial infarction, and ischemic stroke (1899,2147,3323,9402,9405,9408,9409). Clinical research suggests that supplementation with folic acid, pyridoxine, and vitamin B12 decreases homocysteine levels and reduces the atherosclerosis progression in patients at risk for atherosclerosis when compared with placebo (50133,50056,82806). However, other research suggests that elevated homocysteine levels may be a marker, as opposed to a cause, of vascular disease (11387,11388). A 5 µmol/L increase in plasma homocysteine increases the risk of cerebrovascular disease by 50%, and the odds of coronary heart disease by 60% and 80% in males and females, respectively (9407,9411). However, it is not clear if reducing homocysteine levels results in reduced cardiovascular morbidity and mortality (1489,6883,6884,9400,9405,9409,96417). Folic acid, vitamin B6, and vitamin B12 supplementation can reduce total homocysteine from 13.4 to 11 µmol/L. However, this reduction does not seem improve endothelial function or help with secondary prevention of death or myocardial infarction, and some research even suggests an increase in cardiovascular disease (CVD) risk (11387,13482,50373,50314,97619). There is also some debate about whether supplementation with homocysteine-lowering B vitamins can reduce the risk of stroke. A number of large clinical studies and meta-analyses show that supplementation with folic acid, vitamin B6, and vitamin B12, alone or in combination, does not reduce the risk of stroke in patients with CVD or impaired kidney function (11387,13482,50423,83050,96150). However, a more recent meta-analysis of 10 clinical trials including over 44,000 patients shows that B vitamin supplementation reduces the relative risk of stroke by 10% when compared with placebo in patients at risk or with a history of CVD (97619). Also, a meta-analysis in adults with a history of stroke shows that B vitamin supplementation modestly reduces the relative risk of stroke recurrence by 13% and vascular death by 11% when compared with placebo (107136).
• Postherpetic neuralgia. Subcutaneous injections of vitamin B12 seem to reduce postherpetic neuralgia symptoms. Details: Clinical research in patients with subacute herpetic neuralgia shows that subcutaneous injection of vitamin B12 (methylcobalamin) 1000 mcg six times weekly for 4 weeks reduces pain when compared with oral vitamin B12 or subcutaneous lidocaine (90394). Another clinical study shows that administering local subcutaneous injections of methylcobalamin 1000 mcg plus lidocaine up to 20 mg daily for 12 injections over 14 days, starting within 7 days of the onset of subacute ophthalmic herpetic neuralgia, decreases the mean pain score by 63% to 79% when compared with intravenous lidocaine and intramuscular methylcobalamin. Less than 2 patients need to be treated to achieve a pain reduction to ≤3 out of 10. Healing of rash, itching, numbness, and tingling were also improved (96175). Additional clinical research in patients with postherpetic pain and itching shows that this same dosing regimen of subcutaneous vitamin B12 reduces pain and analgesic requirements when compared to baseline (90396).

POSSIBLY INEFFECTIVE

• Age-related cognitive decline. Oral vitamin B12 does not seem to improve cognitive function in older adults when used alone or in combination with other B vitamins. Details: Taking vitamin B12 100-1000 mcg plus folic acid 400-2000 mcg, with or without vitamin B6 3-50 mg, daily for up to about 2 years does not seem to improve tests of cognitive function in adults aged 65 or older, most of whom do not report cognitive impairment at baseline (14392,50225,50510,90392,107140). Also, supplementation with vitamin B12 does not seem to improve cognitive function in elderly individuals with low vitamin B12 levels (12305).
• Alzheimer disease. Oral vitamin B12, when used in combination with other B vitamins, does not seem to improve cognitive function in patients with Alzheimer disease. Details: Clinical research in patients with probable Alzheimer disease using routine medication shows that taking vitamin B12 1 mg, folic acid 5 mg, and vitamin B6 25 mg daily for 18 months does not have a beneficial effect on cognitive function or the severity of disease when compared with placebo. In this study, all patients were consuming a folate-fortified diet (50319). Also, a meta-analysis of clinical research in elderly adults with mild cognitive impairment or dementia shows that taking vitamin B12, usually with other B vitamins, does not improve cognitive function (50510). Observational research has also found that higher vitamin B12 intake over 3 years in a population consuming a folate-fortified diet is not associated with a decreased risk of developing Alzheimer disease (15270). In contrast, preliminary clinical research in patients with probable Alzheimer disease who are not consuming a folate-fortified diet shows that taking vitamin B12 50 mcg daily plus folic acid 1.2 mg daily for 6 months modestly improves some measures of cognitive performance and decreases levels of homocysteine when compared with placebo (107150). More research is needed to determine if any changes in this latter study are clinically relevant.
• Cataracts. Oral vitamin B12 does not seem to reduce cataract development. Details: Clinical research in women with existing cardiovascular disease (CVD) or at increased risk of CVD shows that taking a combination of folic acid 2.5 mg daily, vitamin B6 50 mg daily, and vitamin B12 1 mg daily for an average of 7.3 years does not reduce the risk of cataracts and seems to increase the risk of cataract extraction by 28% when compared with placebo (96149).
• Circadian rhythm sleep disorders. Oral vitamin B12 does not seem to improve sleep disorders. Details: Oral vitamin B12 (methylcobalamin) does not seem to be effective for treating delayed sleep phase syndrome. Methylcobalamin 0.5-1 mg three times daily, with or without bright light therapy, also does not seem to help people with primary circadian rhythm sleep disorders (1344,1345,1346,1347,1348).
• Cognitive impairment. Oral vitamin B12 does not seem to be beneficial for older adults with cognitive impairment. Details: A meta-analysis of clinical research in elderly adults with mild cognitive impairment or dementia shows that taking vitamin B12, usually with other B vitamins, does not improve cognitive function (50510). One clinical trial in elderly people with memory complaints shows that taking a combination of B vitamins, including folic acid 0.8 mg, vitamin B12 0.5 mg, and vitamin B6 (form not specified) 20 mg daily for 24 months reduces cerebral atrophy in the gray matter regions associated with Alzheimer disease by up to seven-fold when compared with placebo. However, this protection does not occur in patients with the lowest average blood levels of homocysteine (90374).
• Fall prevention. Oral vitamin B12 does not seem to reduce the risk of falls. Details: Clinical research shows that taking B vitamins, including folic acid 400 mcg and vitamin B12 500 mcg, daily for 2 years does not prevent falls when compared with placebo in elderly individuals also taking vitamin D (96148).
• Osteoporosis. Oral vitamin B12 does not seem to reduce the risk of osteoporotic fractures. Details: Clinical research in elderly patients or patients with a history of cerebrovascular disease shows that taking vitamin B12 500 mcg and folic acid 0.4-2 mg, with or without vitamin B6 25 mg, daily for 2-3 years does not seem to reduce the risk for osteoporotic fractures when compared with placebo (90377,90393). A 5-7 year follow-up of this research has also found no benefit (103981).
• Physical performance. Oral vitamin B12 does not seem to improve physical performance in older adults. Details: Clinical research shows that taking B vitamins, including folic acid 400 mcg and vitamin B12 500 mcg, daily for 2 years does not increase hand strength or improve performance such as walking when compared with placebo in elderly individuals also taking vitamin D (96148).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related macular degeneration (AMD). Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large-scale clinical study shows that taking vitamin B12 1000 mcg, folic acid 2.5 mg, and vitamin B6 50 mg daily, reduces the risk of developing AMD in females over 40 years of age with a history of cardiovascular disease (CVD) or at least three risk factors for CVD. Those who took this combination for an average of 7.3 years had a 34% reduced risk of developing AMD and a 41% reduced risk of visually significant AMD when compared with placebo (14620). It is unclear if this effect is due to vitamin B12, other ingredients, or the combination.
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if high-dose intramuscular vitamin B12 improves the prognosis of ALS. Details: A clinical study in patients with ALS symptoms for 3 years or less shows that intramuscular vitamin B12 (methylcobalamin) 25-50 mg twice weekly for 3.5 years does not slow functional decline or increase the time until ventilation or death when compared with placebo. However, other clinical research in patients with early-stage ALS shows that intramuscular methylcobalamin 50 mg twice weekly for 16 weeks is associated with slower functional decline and a longer period of time until death or full ventilation when compared with placebo (104947,111556). These effects seem to be particularly notable in fine and gross motor skills, but not bulbar or respiratory functions. Furthermore, vitamin B12 and riluzole slowed clinical progression of ALS more than riluzole alone (111556).
• Angioplasty. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some evidence suggests that vitamin B12 400 mcg, folic acid 1 mg, and vitamin B6 10 mg daily can decrease the rate of restenosis in patients treated with balloon angioplasty (8009,9412,34540). However, this combination does not seem to be as effective for reducing restenosis in patients after coronary stenting (8009). An intravenous loading dose of folic acid, pyridoxine, and vitamin B12 followed by oral administration of folic acid 1.2 mg, pyridoxine 48 mg, and vitamin B12 60 mcg daily after bare metal coronary stenting also does not seem to reduce restenosis and might actually increase restenosis (12150,12151,34540). Due to the lack of evidence of benefit and potential for harm, this combination of vitamins should not be recommended for patients receiving coronary stents (12151). It is unclear if any effects are due to vitamin B12, other ingredients, or the combination.
• Anxiety. Although there is interest in using oral vitamin B12 for anxiety and panic attacks, there is insufficient reliable information about the clinical effects of vitamin B12 for these uses.
• Asthma. Although there is interest in using oral vitamin B12 for asthma, there is insufficient reliable information about the clinical effects of vitamin B12 for this condition.
• Atherosclerosis. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with intermediate risk for coronary heart disease shows that taking vitamin B12 100 mcg, aged garlic extract 250 mg, folic acid 300 mcg, vitamin B6 12.5 mg, and L-arginine 100 mg daily for 12 months reduces coronary artery calcium progression when compared with placebo (88385). It is unclear if this effect is due to vitamin B12, other ingredients, or the combination.
• Atopic dermatitis (eczema). It is unclear if topical vitamin B12 reduces the severity of eczema. Details: Preliminary clinical research shows that applying a specific topical vitamin B12 0.07% cream (Regividerm) twice daily reduces the extent and severity of atopic dermatitis when compared with placebo (15765).
• Attention. Although there is interest in using oral vitamin B12 for improving attention and focus, there is insufficient reliable information about the clinical effects of vitamin B12 for this use.
• Cancer. It is unclear if oral vitamin B12 reduces overall cancer risk when used in combination with other B vitamins. Details: An ancillary clinical study in middle-aged and elderly adults with cardiovascular disease shows that taking a combination of vitamin B12 (cyanocobalamin) 0.02 mg, folic acid 0.56 mg, and vitamin B6 3 mg, with or without eicosapentaenoic acid (EPA) 400 mg plus docosahexaenoic acid (DHA) 200 mg, for a median of 4.7 years does not reduce the risk of cancer when compared with placebo (90666). An additional secondary analysis of clinical research in patients recovering from stroke or transient ischemic attack shows that taking vitamin B12 500 mcg, folic acid 2 mg, and vitamin B6 25 mg daily for around 3.4 years does not reduce the risk of cancer when compared with placebo (90378). The validity of these findings is limited because the studies were not designed nor adequately powered to test for cancer risk.
• Cardiovascular disease (CVD). Oral vitamin B12, taken along with other B vitamins, does not seem to improve secondary prevention of death or myocardial infarction in patients with CVD. However, it might slightly reduce the risk of stroke. Details: Overall evidence from clinical research and meta-analyses shows that taking vitamin B12 in combination with folic acid and/or vitamin B6 does not seem to reduce the risk for secondary death or myocardial infarction in patients with or at risk for CVD (11387,13482,34540,50423,83050,90379,97619). In fact, some research suggests that long-term supplementation with vitamin B6, folic acid, and vitamin B12 for secondary prevention increases the risk of CVD by 20% despite lowering homocysteine levels by 30% (13482). However, other research shows that taking vitamin B12 in combination with other B vitamins modestly reduces the risk of stroke, although results are conflicting (11387,13482,50423,83050,96150,96165,97619,107136). It is unclear which specific combination of B vitamins, if any, might be optimal for reducing stroke risk and which patients are most likely to benefit. In 2001, prior to the publication of the highest quality research on this topic, the US Food and Drug Administration (FDA) approved a qualified health claim stating that, as part of a well-balanced diet that is low in saturated fat and cholesterol, folic acid, vitamin B6, and vitamin B12 may reduce the risk of vascular disease (102368).
• Cervical cancer. It is unclear if oral vitamin B12 reduces cervical cancer risk. Details: Some epidemiological evidence has found that increasing vitamin B12 intake from dietary and supplement sources, along with folic acid, thiamine, and riboflavin, might decrease the risk of precancerous cervical lesions (11074). Also, an analysis of two case control studies has found that increased intake of vitamin B12 is associated with a 75% reduced odds of cervical cancer (34609).
• Chemotherapy-induced peripheral neuropathy. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients receiving chemotherapy shows that a combination of B vitamins that includes vitamin B12 (cyanocobalamin) 1000 mcg, taken daily starting one week prior to treatment and finishing 12 weeks after treatment is completed, does not prevent peripheral neuropathy when compared with placebo (96173).
• Child development. It is unclear if oral vitamin B12 is beneficial for child development. Details: Population research has found that daily dietary intake of less than 2.26 mcg vitamin B12 in the third trimester of pregnancy is associated with an increased risk of poorer outcomes in the offspring for some measures of speech and mathematics ability, including vocabulary at 24 months, combining words at 38 months, speech intelligibility at 6 years, and math comprehension between ages 8-11 years, when compared with dietary intakes of at least 2.26 mcg daily. There was no association between prenatal vitamin B12 intake and reading or spelling abilities, vocabulary at other ages, or full-scale Intelligence Quotient (IQ) at ages 8 or 15 (107143). Furthermore, a very large clinical study in infants of pregnant adults, 71% of whom were deficient in vitamin B12 at baseline, shows that taking vitamin B12 50 mcg daily starting in early pregnancy (<15 weeks gestation) until 6 months postpartum does not improve neurodevelopment as measured by language, motor, socioemotional, or cognitive scores at 12 months old and may worsen early motor performance at 8-12 weeks when compared with placebo. However, the negative effects on motor performance resolved by 6 and 12 months of age (112431).
• Child growth. Oral vitamin B12 taken by pregnant adults does not seem to be beneficial for infant growth. Details: A very large clinical study in infants of pregnant adults, 71% of whom were deficient in vitamin B12 at baseline, shows that taking vitamin B12 50 mcg daily starting in early pregnancy (<15 weeks gestation) until 6 months postpartum does not improve the infant's linear growth, length, or weight at 12 months of age (112431).
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral vitamin B12 reduces the risk of COPD. Details: Clinical research in patients with COPD shows that taking vitamin B12 500 mg daily for 8 weeks modestly improves endurance on the cycle ergometer, but does not improve oxygen consumption, when compared with placebo (96172).
• Cognitive function. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in healthy, middle-aged adults shows that taking a combination product containing vitamin B12, other B vitamins, bacopa, and gingko biloba twice daily for 12 weeks does not improve measures of memory, attention, cognition, mood, or stress reactivity when compared with placebo (111334).
• Colorectal cancer. It is unclear if oral vitamin B12 reduces colorectal cancer risk. Details: Some epidemiological evidence has found that increased dietary intake of vitamin B12 is associated with a reduced risk of developing colorectal cancer (90383). However, preliminary clinical research shows that taking vitamin B12 1 mg, folic acid 2.5 mg, and vitamin B6 50 mg daily for up to 7.3 years does not reduce the risk of colorectal adenoma in females at high risk for cardiovascular disease (90389). Furthermore, a secondary analysis of clinical research in elderly patients suggests that taking vitamin B12 500 mcg and folic acid 400 mcg daily for 2 years might increase the risk of colorectal cancer when compared with placebo (90393).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral vitamin B12 is beneficial for patients with COVID-19. Details: A small observational study in hospitalized patients with COVID-19 pneumonia has found that higher plasma vitamin B12 levels may be associated with an increased risk of transfer to intensive care or death than lower plasma levels. However, when multivariate regression was conducted, only patient age was associated with worsened outcomes. Additionally, the total study population was small, with only nine of 49 patients experiencing the worsened outcomes (107138).
• Dementia. It is unclear if oral vitamin B12 reduces the risk of developing dementia. Details: A large cohort of Danish adults has found that vitamin B12 levels or intake does not seem to impact the risk of developing Alzheimer disease or other dementias (104922). However, vitamin B12 might be beneficial in specific patient populations. A small observational study in patients with Parkinson disease has found that higher vitamin B12 levels (648.5 ng/L) are associated with a lower risk of developing dementia when compared with lower vitamin B12 levels (452 ng/L) (103975). It is not yet known if supplementation with vitamin B12 reduces the risk for dementia in these patients.
• Depression. It is unclear if oral vitamin B12 is beneficial for reducing depression risk. Details: A meta-analysis of epidemiological research has found that the highest dietary intake of vitamin B12 is associated with a 14% reduced risk of depression. However, in a sub-analysis, this association was not significant in males (107133). In contrast, one epidemiological study in older males included in the analysis has found that daily dietary intake of at least 4.79 mcg vitamin B12 is linked with a 58% lower risk of depression when compared with daily intake of less than 3.16 mcg. In this study, this inverse association was not observed in females (96168). Other observational research has found that low-normal serum vitamin B12 levels are associated with a 3.8 times increased risk for depression during pregnancy when compared with normal vitamin B12 levels (102384). It is unclear if increased intake of vitamin B12 through the diet or supplements reduces the risk for depression or is beneficial for treating symptoms of depression in any population. However, a meta-analysis of clinical research in elderly populations shows that supplementation with vitamin B12 100-1000 mcg daily, usually in combination with folic acid 400-2000 mcg daily, does not reduce symptoms of depression. Most individuals in these studies were not specifically diagnosed with depression (107140).
• Diabetes. It is unclear if oral vitamin B12 improves glycemic indices or prevents loss of skeletal muscle in patients with diabetes. Details: A small clinical study in patients with diabetes in India who are stabilized on metformin and/or a sulfonylurea shows that taking vitamin B12 (methylcobalamin) 500 mcg with or without folic acid 5 mg daily for 8 weeks seems to reduce glycated hemoglobin (HbA1C) by 1.3% to 1.5%, compared with a 0.3% increase with placebo (104917). This study is limited due its small sample size and lack of blinding. In elderly adults with type 2 diabetes, population research has found a lower dietary intake of vitamin B12 (average of 11.2 mcg daily) in individuals with a loss of skeletal muscle mass of at least 1.2%, compared with an average intake of 13.4 mcg daily in those with a skeletal muscle mass loss of less than 1.2%. However, further analysis determined that any relationship between vitamin B12 intake and loss of skeletal muscle mass was only significant in individuals with insufficient energy intake overall (107151).
• Diabetic neuropathy. Small clinical studies suggest that oral vitamin B12 may modestly improve pain in patients with diabetic neuropathy. Details: Two small clinical studies in patients with diabetic peripheral neuropathy show that taking vitamin B12 (methylcobalamin) 1-1.5 mg for 4-12 months modestly improves pain when compared with baseline or placebo (82841,104923). Some research also shows that vitamin B12 may be beneficial in combination with other ingredients. Studies have evaluated products containing vitamin B12 (methylcobalamin or cyanocobalamin), benfotiamine, and vitamin B6 daily for 9-12 weeks (82931,82939); and vitamin B12 (methylcobalamin) 2 mg, folic acid (L-methylfolate) 3 mg, and vitamin B6 (pyridoxal-5'-phosphate) 35 mg (Metanx; Pamlab) daily for 24 weeks (90375).
• Diarrhea. It is unclear if oral vitamin B12 is beneficial for reducing diarrhea in children. Details: Preliminary clinical research in children aged 6-30 months from low- and middle-income countries shows that taking vitamin B12 at twice the recommended dietary allowance, with or without folic acid, does not reduce the risk for diarrhea when compared with placebo (90391).
• Fatigue. It is unclear if intramuscular vitamin B12 is beneficial for improving well-being in those with fatigue or tiredness. Details: A small crossover trial in patients complaining of tiredness or fatigue shows that receiving intramuscular injections of vitamin B12 (hydroxocobalamin) 5 mg twice weekly for 2 weeks seems to improve general well-being and happiness, and has a trend toward improving fatigue, when compared with placebo (10127). The validity of this study is limited by a large drop-out rate and unstandardized outcome measures.
• Hearing loss. Oral vitamin B12 has only been evaluated in combination with adenosine triphosphate; its effect when used alone is unclear. Details: A small observational study in adults with idiopathic sudden sensorineural hearing loss has found that taking vitamin B12 1.5 mg with adenosine triphosphate 300 mg daily for 8-16 weeks is associated with modestly reduced hearing loss at 4-6 months after starting treatment when compared with taking the combination for less than 8 weeks (104924). This finding is limited due to its observational nature and lack of a control group.
• Hepatitis C. It is unclear if intramuscular vitamin B12 is beneficial for sustaining viral response in patients with chronic hepatitis C infection. Details: A small clinical study in patients with chronic hepatitis C infection shows that intramuscular vitamin B12 (cyanocobalamin) 5000 mcg every 4 weeks along with standard care improves sustained viral response when compared with standard of care alone (90386).
• Hypertriglyceridemia. It is unclear if oral vitamin B12 is beneficial for reducing triglyceride levels. Details: Some evidence shows that taking vitamin B12 7.5 mcg with fish oil 5 grams might be superior to fish oil alone when used daily to reduce total serum cholesterol and triglycerides. This suggests vitamin B12 might have an independent effect in lowering serum cholesterol and triglycerides, but further investigation is needed to confirm this effect (8694).
• Hypotension. It is unclear if oral vitamin B12 is beneficial for treating hypotension. Details: A meta-analysis of 3 observational studies in patients hospitalized with hypotension secondary to cardiac surgery vasoplegia suggests that administration of intravenous vitamin B12 (hydroxocobalamin) is associated with an 8 mmHg higher mean arterial pressure (MAP) at 1 hour but no change in vasopressor dosage at 1 hour or mortality rate when compared with methylene blue (112264). The validity of these findings is limited by the inclusion of only retrospective studies.
• Infant development. It is unclear if taking oral vitamin B12 during pregnancy is beneficial for improving infant development. Giving oral vitamin B12 to infants does not seem to be beneficial. Details: Clinical research shows that supplementation with vitamin B12 50 mcg daily from less than 14 weeks gestation until 6 weeks postpartum does not improve cognitive development in infants by 9 months of age when compared with placebo (96174). When these children were evaluated at 30 months of age, a very small benefit of vitamin B12 on expressive language was identified; however, there was no effect on cognition, receptive language, fine motor skills, or gross motor skills (100169). It is unknown whether a longer duration of postpartum supplementation or supplementation in specific populations might be beneficial. Vitamin B12 supplementation in infants has also been evaluated. A large clinical trial in marginally stunted Nepalese infants aged 6-11 months shows that giving vitamin B12 (cyanocobalamin) 2 mcg daily for 12 months reduces homocysteine levels, but does not improve motor or cognitive development, when compared with placebo (104926).
• Inflammatory bowel disease (IBD). Although there is interest in using oral vitamin B12 for IBD, there is insufficient reliable information about the clinical effects of vitamin B12 for this condition.
• Lung cancer. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: The association between vitamin B12 and lung cancer is unclear. Some population research found no relationship between blood levels of vitamin B12 and lung cancer (9454). However, other observational research involving over 5,000 case-control pairs found that higher vitamin B12 levels are linked with an increased risk for lung cancer (102383). It is unclear if increased intake of vitamin B12, either through the diet or supplementation, directly affects the risk of lung cancer.
• Male infertility. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A retrospective study in adult males with idiopathic and varicocele-related infertility suggests that taking a combination product containing vitamin B12 1.5 mcg, L-carnitine, acetyl L-carnitine, citric acid, selenium, coenzyme Q10, vitamin C, zinc, and folic acid (Proxeed Plus) twice daily for 6 months is associated with improvements in ejaculate volume, sperm count, sperm concentration, total motility, and progressive motility in patients with idiopathic infertility when compared to baseline. However, improvement in sperm morphology was lacking. Furthermore, patients with more severe varicocele seem to benefit most, especially with regard to progressive motility (111296). The validity of these findings is limited by a lack of comparator group. Further, it is unclear if these effects are due to vitamin B12, other ingredients, or the combination.
• Mastalgia. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with mastalgia shows that taking a combination of vitamin B12 as methylcobalamin 100 mg, gamma-linolenic acid, and vitamin C daily for 12 weeks does not improve the proportion of patients with minimal or no pain when compared with placebo (111059).
• Multiple sclerosis (MS). Although there is interest in using oral vitamin B12 for MS, there is insufficient reliable information about the clinical effects of vitamin B12 for this condition.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral vitamin B12 is beneficial for NAFLD. Details: A small clinical study in adults with NAFLD shows that taking vitamin B12 1000 mcg daily for 12 weeks reduces serum levels of homocysteine but has no effect on serum aminotransferases, measures of steatosis, fibrosis scores, fasting blood glucose, serum insulin, measures of insulin resistance, triglycerides, low-density lipoprotein (LDL) cholesterol, or high-density lipoprotein (HDL) cholesterol when compared with placebo (111555).
• Pancreatic cancer. It is unclear if oral vitamin B12 is beneficial for reducing the risk of pancreatic cancer. Details: Most population research has found that increased intake of vitamin B12, as a supplement or in the diet, is not associated with a reduced risk of pancreatic cancer (9327,104927). However, a small, retrospective population study in which smoking and non-smoking adults recalled past eating habits found that increased dietary intake of vitamin B12 is associated with a 33% reduction in pancreatic cancer risk (97976). These conflicting findings may be related to study methodology, as well as the age, gender, or smoking status of the included patients.
• Periodontitis. Although there is interest in using oral vitamin B12 for periodontitis, there is insufficient reliable information about the clinical effects of vitamin B12 for this condition.
• Peripheral neuropathy. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific product containing vitamin B12 3 mcg, folic acid 400 mcg, and uridine monophosphate 50 mg (Keltican) daily for 60 days reduces pain by 44% and decreases analgesic use by over 75% when compared to baseline in patients with peripheral neuropathy, including those with lumbar/lumbosacral radiculopathy, sciatic pain, and cervical radiculopathy (90384). The validity of this finding is limited by the lack of a control group. Furthermore, it is unclear if the benefits are due to vitamin B12, other ingredients, or the combination.
• Psoriasis. Topical vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that a specific cream containing vitamin B12 and avocado oil (Regividerm, Regeneratio Pharma AG) reduces symptoms of psoriasis as effectively as calcipotriol ointment (Psorcutan) after 12 weeks of therapy. The vitamin B12 combination cream also causes less irritation than calcipotriol (14909). It is unclear if the benefits are due to vitamin B12, other ingredients, or the combination.
• Respiratory tract infections. A small study suggests that oral vitamin B12 does not reduce the rate of respiratory tract infections in children. Details: Preliminary clinical research in children aged 6-30 months from low-and middle-income countries suggests that taking vitamin B12 at twice the recommended dietary allowance with or without folic acid does not reduce the risk for lower respiratory tract infections when compared with placebo (90391).
• Schizophrenia. Oral vitamin B12 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination of vitamin B12 400 mcg and folic acid 2 mg daily for 16 weeks improves negative symptoms when compared with placebo in patients with schizophrenia who have persistent symptoms and a specific genetic variant of the folate transporter gene FOLHI. This variant normally results in reduced folate absorption. However, in patients without this genetic variant, folate is not beneficial with respect to negative symptom improvement (90387).
• Sickle cell disease. Oral vitamin B12 has only been evaluated in combination with other B vitamins; its effect when used alone is unclear. Details: Preliminary clinical research in adults with sickle cell disease shows that taking vitamin B12 4.2-6 mcg, folic acid 700 mcg, and vitamin B6 4.2-6 mg daily might lower homocysteine levels. However, it is unknown if this will reduce the risk of endothelial damage in these patients (9324).
• Stroke. It is unclear if oral vitamin B12, either alone or with other B vitamins, is beneficial for stroke prevention. Details: Epidemiological research has found that people with a higher intake of vitamin B12 from dietary sources do not have a reduced risk of ischemic or hemorrhagic stroke (14316). A number of clinical studies and meta-analyses show that supplementation with folic acid, vitamin B6, and vitamin B12, alone or in combination, does not reduce the risk of stroke in patients with cardiovascular disease (CVD) or impaired kidney function (11387,13482,50420,50423,83050,90379,90380,96150). However, a more recent meta-analysis of 10 clinical trials including over 44,000 patients shows that B vitamin supplementation modestly reduces the relative risk of stroke by 10% when compared with placebo in patients at risk or with a history of CVD (97619). This meta-analysis differed from some of the earlier analyses due to the inclusion of several additional clinical trials. Also, a meta-analysis in adults with a history of stroke shows that B vitamin supplementation modestly reduces the relative risk of stroke recurrence by 13% and vascular death by 11% when compared with placebo (107136). In 2001, prior to the publication of the highest quality research on this topic, the US Food and Drug Administration (FDA) allowed a qualified health claim stating that, as part of a well-balanced diet that is low in saturated fat and cholesterol, folic acid, vitamin B6, and vitamin B12 may reduce the risk of vascular disease (102368). Unfortunately, even after the publication of higher quality research, it is still unclear which specific combination of B vitamins is optimal and which patients are most likely to benefit. One network meta-analysis suggests that a combination of folic acid and vitamin B6 lowers the risk of stroke more effectively than B vitamin mixtures that include vitamin B12 (96165). However, this analysis is limited because it didn't account for dosing. Another meta-analysis suggests that exposure to low, but not high, amounts of vitamin B12 (cyanocobalamin) seems to reduce stroke risk (96150).
• Tinnitus. It is unclear if intramuscular vitamin B12 is beneficial in patients with tinnitus. Details: A small clinical study shows that intramuscular vitamin B12 2500 mcg weekly for 6 weeks reduces tinnitus severity by 22% when compared to baseline in patients with chronic tinnitus and vitamin B12 deficiency, but not in patients with normal levels of vitamin B12. Vitamin B12 does not improve pitch or volume in either group of patients (96170). The validity of this finding is limited by the lack of a control group.
• Venous thromboembolism (VTE). It is unclear if oral vitamin B12 is beneficial for preventing VTE. Details: Epidemiological research has found that low levels of vitamin B12 are associated with an increased risk for VTE. However, clinical trials evaluating the use of B vitamins for prevention of VTE have shown conflicting results (90398). More evidence is needed to rate vitamin B12 for these uses.

(Read more about VITAMIN B12)

LIKELY SAFE ...when used orally in food amounts. Amaranth seed and leaves are commonly used in foods (3833,5063,31069,31083,104835).

POSSIBLY SAFE ...when used orally as medicine, short-term. Amaranth oil 20 mL has been used daily with apparent safety for up to 3 weeks (104834,104836,104837).

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

(Read more about AMARANTH)

LIKELY SAFE ...when used orally in food amounts (14145). There is insufficient reliable information available about the safety of broccoli when used in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts (14145). There is insufficient reliable information available about the safety of broccoli when used in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about BROCCOLI)

POSSIBLY SAFE ...when used orally and appropriately (11438,11442).

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

(Read more about BUCKWHEAT)

LIKELY SAFE ...when used orally in amounts commonly found in foods (104531,104532).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Chia has been used safely at doses up to 40 grams daily for up to 6 months (16124,97940). ...when used topically, short-term. A product containing chia seed oil 4% has been applied to the skin safely for up to 8 weeks (25537).

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

(Read more about CHIA)

LIKELY SAFE ...when ground flaxseed is used orally and appropriately. Ground flaxseed has been safely used in numerous clinical trials in doses up to 30-60 grams daily for up to 1 year (6803,6808,8020,10952,10978,12908,12910) (16760,16761,16762,16765,16766,18224,21191,21194,21196,21198) (21199,21200,22176,22179,22180,22181,65866,66065) (101943,101949,101950).

POSSIBLY SAFE ...when flaxseed lignan extract or mucilage is used orally and appropriately. Some clinical research shows that a specific flaxseed lignan extract (Flax Essence, Jarrow Formulas) 600 mg daily can be used with apparent safety for up to 12 weeks (16768). Additional clinical research shows that other flaxseed lignin extracts can be used with apparent safety for up to 6 months (21193,21197,21200). In one clinical trial, flaxseed mucilage was used with apparent safety at a dose of up to 5120 mg daily for up to 12 weeks (108047)....when flaxseed is used topically in a warm poultice (101946).

POSSIBLY UNSAFE ...when raw or unripe flaxseed is used orally. Raw flaxseed contains potentially toxic cyanogenic glycosides (linustatin, neolinustatin, and linamarin); however, these glycosides have not been detected after flaxseed is baked (5899). Unripe flaxseeds are also thought to be poisonous when consumed due to cyanide content.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Flaxseed can have mild estrogenic effects. Theoretically, this might adversely affect pregnancy (9592,12907); however, there is no reliable clinical evidence about the effects of flaxseed on pregnancy outcomes.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about FLAXSEED)

LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods.

POSSIBLY SAFE ...when the seed or seed oil is used orally and appropriately in medicinal amounts, short-term. Pumpkin seed has been used with apparent safety in a dose of up to 10 grams daily for up to 12 months (92383). Pumpkin seed oil has been used with apparent safety in a dose of up to 400 mg daily for up to 6 months (92378). There is insufficient reliable information available about the safety of pumpkin seed oil when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.

(Read more about PUMPKIN)

LIKELY SAFE ...when used orally in food amounts. Quinoa is a common food source for many people (99147,99148,99149). There is insufficient reliable information available about the safety of quinoa when used in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts. There is insufficient reliable information available about the safety of quinoa in medicinal amounts; avoid using.

(Read more about QUINOA)

LIKELY SAFE ...when used orally in amounts commonly found in food. Sesame has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when sesame oil is used orally and appropriately, short-term. Sesame oil has been used with apparent safety in doses up to 35 grams daily for up to 12 weeks (96179,96180,108354). The sesame constituent sesamin has been used with apparent safety at doses of 200 mg daily for 6 weeks (103230) and 10 mg daily for 12 weeks (99863). Sesame oil 150 mL has also been administered via nasogastric tube with apparent safety as a single dose (27645). ...when sesame oil is used in a nasal spray, short-term. A specific nasal spray (Nozoil) containing sesame oil has been used with apparent safety for up to 20 days (27658,27659,27660). ...when sesame oil is applied topically (96178,103227,103228). There is insufficient reliable information available about the safety of other forms of sesame when used in medicinal amounts.

CHILDREN: POSSIBLY SAFE
when sesame oil is used orally and appropriately in medicinal amounts, short-term. Sesame oil 5 mL has been used safely at bedtime for up to 3 days (27647).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of sesame when used in medicinal amounts during pregnancy and lactation.

(Read more about SESAME)

LIKELY SAFE ...when consumed in food amounts (18). Although the fruit contains cyanogenic glycosides, the concentrations are very low (18). There is insufficient reliable information available about the safety of sorghum used in amounts larger than those found in foods.

PREGNANCY AND LACTATION:
Insufficient reliable information available.

(Read more about SORGHUM)

LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods. When used as a substitute for other dietary oils, the recommended intake of high-oleic acid sunflower oil is 20 grams (1.5 tablespoons) daily (9780,98563). ...when used topically and appropriately, short-term. Sunflower oil has been applied to the skin twice daily for up to 6 weeks (76687). There is insufficient reliable information available about the safety of sunflower oil when used as an oral rinse.

CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.

CHILDREN: POSSIBLY SAFE
when applied topically and appropriately, short-term. Sunflower oil has been applied to the skin of infants daily for up to 2 months (96144,96145,105524,108143). There is insufficient reliable information available about the safety of sunflower oil when used orally in larger amounts as medicine.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods. There is insufficient reliable information available about the safety of sunflower oil when used in amounts greater than those found in food.

(Read more about SUNFLOWER OIL)

LIKELY SAFE ...when used orally, topically, intravenously, intramuscularly, or intranasally and appropriately. Vitamin B12 is generally considered safe, even in large doses (15,1344,1345,1346,1347,1348,2909,6243,7289,7881)(9414,9416,10126,14392,15765,82832,82949,82860,82864,90386)(111334,111551).

PREGNANCY: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA). The RDA for vitamin B12 during pregnancy is 2.6 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 during pregnancy.

LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the recommended dietary allowance (RDA). The RDA of vitamin B12 during lactation is 2.8 mcg daily (6243). There is insufficient reliable information available about the safety of larger amounts of vitamin B12 while breastfeeding.

(Read more about VITAMIN B12)

(Read more about AMARANTH)

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP1A2.  Details Pharmacokinetic research in humans shows that eating 500 grams of fresh broccoli daily for 6-12 days can increase CYP1A2 activity by 10% to 200% (19608,95722). Induction of CYP1A2 activity by broccoli is attributed to its glucosinolate constituents (19608).

CYTOCHROME P450 2A6 (CYP2A6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, broccoli might reduce the levels and effects of drugs metabolized by CYP2A6.  Details Pharmacokinetic research in humans shows that eating 500 grams of broccoli daily for 6 days increases CYP2A6 activity by 135% to 550%. Induction of CYP2A6 activity is attributed to its glucosinolate constituents (19608).

(Read more about BROCCOLI)

(Read more about BUCKWHEAT)

(Read more about CHIA)

ANTIBIOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, antibiotics might interfere with the metabolism of flaxseed constituents, which could potentially alter the effects of flaxseed.  Details Some potential benefits of flaxseed are thought to be due to its lignan content. Secoisolariciresinol diglucoside (SDG), a major lignan precursor, is found in high concentrations in flaxseed. SDG is converted by bacteria in the colon to the lignans enterolactone and enterodiol (5897,8022,8023,9592). Antibiotics alter the flora of the colon, which could theoretically alter the metabolism of flaxseed.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, using flaxseed in combination with anticoagulant or antiplatelet drugs might have additive effects and increase the risk of bleeding.  Details Some clinical evidence suggests that the oil contained in flaxseed can decrease platelet aggregation (5898,21912).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, flaxseed might have additive effects when used with antidiabetes drugs and increase the risk for hypoglycemia.  Details Some clinical research suggests that flaxseed can lower blood glucose levels (5899,10978,21194,21196,111061).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, flaxseed might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.  Details Clinical research shows that daily flaxseed consumption, especially for longer than 12 weeks, modestly reduces blood pressure (21197,26487,96426,96428,111063).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking flaxseed might decrease the effects of estrogens.  Details Flaxseed contains lignans with mild estrogenic and possible antiestrogenic effects. The lignans seem to compete with circulating endogenous estrogen and might reduce estrogen binding to estrogen receptors, resulting in an anti-estrogen effect (8868,9593). It is unclear if this effect transfers to exogenously administered estrogens.

(Read more about FLAXSEED)

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Pumpkin might reduce excretion and increase levels of lithium.  Details Pumpkin is thought to have diuretic properties (92383). Theoretically, this might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

(Read more about PUMPKIN)

(Read more about QUINOA)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Taking sesame oil with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical studies show that sesame oil can decrease plasma glucose and glycated hemoglobin (HbA1c) levels. Some clinical research in patients taking glibenclamide shows that using sesame oil or a blend of sesame oil and rice bran oil in place of other oil for cooking reduces plasma glucose more than glibenclamide alone (27654,28139,96177,108350,108352,108355). Monitor blood glucose levels closely. Dose adjustments might be necessary.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Taking sesame oil with antihypertensive drugs might increase the risk of hypotension.  Details Clinical research shows that replacing other cooking oil with sesame oil can lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with or without hypertension. There is also some evidence that sesame oil has additive effects in patients also taking atenolol, nifedipine, and/or hydrochlorothiazide (27652,27654,27655,96179,108355,108357). In patients using nifedipine, using a blend of sesame oil and rice bran oil for cooking reduces both SBP and DBP more than nifedipine alone (96180).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, sesame might increase the levels and clinical effects of CYP2C9 substrates.  Details In vitro, sesame inhibits CYP2C9 (11028). However, this interaction has not been reported in humans.

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, sesame might alter the transport of P-glycoprotein substrates.  Details In vitro research suggests that sesamin, a constituent of sesame, can inhibit the multi-drug transporter protein, P-glycoprotein (28319,28320). However, this interaction has not been reported in humans.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, sesame might interfere with tamoxifen.  Details In animal research, sesame seed reduces the tumor-inhibitory effect of tamoxifen by reducing apoptosis and increasing proliferation (28110,28111). This interaction has not been reported in humans.

(Read more about SESAME)

(Read more about SORGHUM)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, sunflower oil might decrease the effectiveness of antidiabetes medications.  Details A diet using sunflower oil as a fat source can cause increased fasting blood glucose levels in patients with type 2 diabetes (8132). Dose adjustments to diabetes medications might be necessary.

(Read more about SUNFLOWER OIL)

(Read more about VITAMIN B12)

General ...Orally, amaranth seed and amaranth oil have been used with apparent safety in clinical research (6188,5063,31069,92235,104835,104835,104836,104837); however, most studies have not conducted a thorough evaluation of safety outcomes. One case of anaphylaxis related to consumption of amaranth seed from Amaranthus cruentus has been reported (99233).

Immunologic ...Orally, a case of anaphylaxis in a 60-year-old female was confirmed to be related to consumption of amaranth seed from Amaranthus cruentus (99233).

(Read more about AMARANTH)

General ...Broccoli is well tolerated when consumed as food. A thorough evaluation of safety outcomes when broccoli is taken as medicine has not been conducted.

Dermatologic ...Topically, allergic reactions to broccoli have caused contact dermatitis (14158).

Gastrointestinal ...Orally, loose stools, diarrhea, abdominal pain, and abdominal cramping have been reported following intake of broccoli seed and sprout extracts, particularly at high doses (114753).

Hepatic ...In one case report, a 56-year-old adult developed elevated transaminases, with alanine aminotransferase (ALT) 5. 8 times above normal, aspartate aminotransferase (AST) 2.4 times above normal, and gamma-glutamyl transpeptidase (GGT) 5.1 times above normal. This was thought to be related to the consumption of 800 mL of broccoli juice daily over a 4-week period. Values returned to normal 15 days after cessation of juice consumption (96191).

Immunologic ...Topically, allergic reactions to broccoli have caused contact dermatitis (14158).

(Read more about BROCCOLI)

General ...Orally, buckwheat seems to be well tolerated (11438,11442). However, allergic reactions to buckwheat can occur in some adults and children. Symptoms can include skin sensitization, allergic rhinitis, asthma, conjunctivitis, nausea, vomiting, and anaphylaxis (11435,11436,11437,96060,96061). Occupational exposure to buckwheat, or household exposure through sleeping on a buckwheat husk stuffed-pillow can cause sensitization, of which symptoms include allergic rhinitis and asthma (11437,11443).

Immunologic ...Orally, buckwheat seems to be well tolerated (11438,11442). However, allergic reactions to buckwheat can occur in some adults and children. Symptoms can include skin sensitization, allergic rhinitis, asthma, conjunctivitis, nausea, vomiting, and anaphylaxis (11435,11436,11437,96060,96061).
Occupational exposure to buckwheat, or household exposure through sleeping on a buckwheat husk stuffed-pillow can cause sensitization, of which symptoms include allergic rhinitis and asthma (11437,11443).

(Read more about BUCKWHEAT)

General ...Orally and topically, chia seems to be well tolerated.
Most Common Adverse Effects:
Orally: Flatulence and soft stools.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Cardiovascular ...Chia contains a high concentration of alpha-linolenic acid (ALA). There is some concern that ALA might increase triglyceride levels more than other omega-3 fatty acids (12918); however, clinical research with a specific variety of chia called Salba shows that it does not significantly increase triglyceride levels (16124).

Gastrointestinal ...Orally, chia might cause mild gastrointestinal adverse effects. Some patients consuming chia 40 grams daily for up to 6 months reported mild and transient gastrointestinal adverse effects such as flatulence and soft stools; however, the frequency of these adverse effects was similar to patients consuming an oat bran control (97940). Bloating and flatulence have been reported with a chia flour-based sports beverage (112385).

Immunologic ...Orally, chia might cause anaphylaxis in sensitive individuals. A single case of IgE-mediated anaphylactic reaction has been reported for a patient who consumed chia seeds. Symptoms, including pruritus in the mouth, urticaria, facial angioedema, shortness of breath, and dizziness, developed a few days after consuming chia seeds. The reaction was attributed to sensitivity to proteins in chia seeds (91517).

Oncologic ...Chia seeds contain a high concentration of alpha-linolenic acid (ALA). Epidemiologic research suggests that high dietary intake of ALA might increase risk for prostate cancer (1337,2558,7823,7147,12978). Other research suggests high intake or serum levels of ALA does not increase the overall risk of prostate cancer (12961,15736); however, it might increase the risk of advanced prostate cancer (12961). Association with prostate cancer appears to depend on the sources of ALA. Dairy and meat sources have been positively associated with prostate cancer, whereas plant sources, such as chia seed, don't seem to affect prostate cancer risk (12909). According to a clinical trial, intake of ALA does not appear to increase levels of prostate specific antigen (PSA) (91402).

(Read more about CHIA)

General ...Orally, flaxseed is usually well-tolerated.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, gastrointestinal complaints.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions such as and anaphylaxis.

Gastrointestinal ...Integrating flaxseed in the diet can cause digestive symptoms similar to other sources of dietary fiber including bloating, fullness, flatulence, abdominal pain, diarrhea, constipation, dyspepsia, and nausea (12910,16761,16765,21198,21200,22176,22179,65866,101943). Higher doses are likely to cause more gastrointestinal side effects. Flaxseed can significantly increase the number of bowel movements and the risk for diarrhea (6803,8021,16765). Doses greater than 45 grams per day may not be tolerated for this reason (6802). Metallic aftertaste and bowel habit deterioration have also been reported in a clinical trial (21198).
There is some concern that taking large amounts of flaxseed could result in bowel obstruction due to the bulk forming laxative effects of flaxseed. Bowel obstruction occurred in one patient in a clinical trial (65866). However, this is not likely to occur if flaxseed is consumed with an adequate amount of fluids.

Immunologic ...Occasionally, allergic and anaphylactic reactions have been reported after ingestion of flaxseed (16761). Handling and processing flaxseed products might increase the risk of developing a positive antigen test to flaxseed and hypersensitivity (6809,12911,26471,26482).

Oncologic ...Flaxseed contains alpha-linolenic acid (ALA). High dietary intake of ALA has been associated with increased risk for prostate cancer (1337,2558,7823,7147,12978). However, ALA from plant sources, such as flaxseed, does not seem to increase this risk (12909).

Other ...Orally, partially defatted flaxseed, which is flaxseed with less alpha-linolenic acid, might increase triglyceride levels (6808). Raw or unripe flaxseed contains potentially toxic cyanogenic glycosides (linustatin, neolinustatin, and linamarin). These chemicals can increase blood levels and urinary excretion of thiocyanate in humans. However, these glycosides have not been detected after flaxseed is baked (5899).

(Read more about FLAXSEED)

General ...Orally, pumpkin products are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, diarrhea, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Dermatologic ...There are two case reports of adult females developing substantial transient hair loss 1-3 weeks after consumption of a meal containing either bitter-tasting pumpkin or undefined squash. This adverse effect was attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Gastrointestinal ...Orally, pumpkin seed oil has been reported to cause mild abdominal discomfort in clinical trials (5093,92378). There are also two case reports of adults developing severe nausea, vomiting, and diarrhea following consumption of a meal containing either bitter-tasting pumpkin or undefined squash. These adverse effects were attributed to a high concentration of cucurbitacin, which is commonly found in wild pumpkins (104535).

Immunologic ...Orally, pumpkin seed oil and pumpkin pulp have been reported to cause anaphylactic reactions in children and adults. A case review highlights 4 cases of anaphylaxis in children (3 from pumpkin pulp, 1 from pumpkin seeds), and 7 cases in adults (1 from pumpkin flesh, 6 from pumpkin seeds). Symptoms of anaphylaxis include urticaria, angioedema of the lips or face, dyspnea, dysphagia, and oropharyngeal itching and swelling. A case report describes a 2-year-old male presenting with urticaria, swollen lips, and increased dyspnea 10 minutes after ingesting pumpkin seeds. The patient was found to have elevated allergen-specific immunoglobulin E (IgE) and a positive skin-prick test for pumpkin seeds. Symptoms resolved after treatment with epinephrine, systemic glucocorticoids, salbuterol, and antihistamines (107843).
There may also be concern for allergic reaction due to inhalation or topical exposure. One case report describes an 8-year-old child developing anaphylaxis while carving a pumpkin; another highlights that inhalation of pumpkin seed flour may have potentiated anaphylaxis in 3 individuals following the ingestion of pumpkin seeds (107843). Further research is necessary to assess the relationship between anaphylaxis and route of administration.

(Read more about PUMPKIN)

General ...Orally, quinoa seems to be well-tolerated. Rarely, quinoa can cause allergic reaction in some individuals, including anaphylaxis (99150,99151,96062).

Immunologic ...Orally, allergic reactions to quinoa have been reported (99150,96062). Anaphylaxis and pruritic reactions have occurred in at least two individuals, a 29-year-old female and a 52-year-old male. Quinoa allergy was confirmed in both patients via skin-prick testing with quinoa extract (99150,99151).

(Read more about QUINOA)

General ...Orally, topically, or intranasally, sesame seems to be well tolerated.
Most Common Adverse Effects:
All routes of administration: Allergic reactions.

Dermatologic ...In a small clinical study, one patient using a cream containing sesame oil as well as aqueous extracts of guggul and Allium ampeloprasum complained of rash at the application site (105751). It is unclear if this reaction was due to sesame, other ingredients, or other factors.

Gastrointestinal ...There was a single case of diarrhea associated with oral sesame in a clinical trial (108356).

Immunologic ...Multiple cases of allergic response to sesame seed occurring after occupational, topical, intramuscular, or oral exposure have been reported (28157,28158,28159,28160,28161,28162,28163,28166,28167,28183)(28184,28185,28186,28188,108348). One study found that up to 0.5% of the United States population reports having a sesame allergy, and 0.23% of the population meets criteria for an IgE-mediated allergic reaction to sesame (100501). Allergic symptoms may be dermatologic, such as angioedema (28160,28167,108348), cheilitis (28207), dermatitis (28157,28166,28182,28185,28186), edema (28159), erythema (28167), pruritis (28167,108348), purpura (28188), flushing (108348), and urticaria (28159,28160,28162,108348); musculoskeletal (28188); respiratory, such as asthma (28159,28162), rhinitis (28162), wheezing (28167), and general breathing difficulties (108348); gastrointestinal, such as vomiting (28159,108348); and others such as conjunctivitis (28159), anaphylactic shock (28157,28159,28160,28167,28177,28178,28179,28180,28204,108348), and hemodynamic modifications (28169). In Canada, sesame accounted for 4% of pediatric food-induced anaphylaxis reactions presenting to emergency departments over a 10-year period. The majority of cases were mild to moderate in severity and occurred within 2 hours of exposure; however, about 3% occurred 2-8 hours after exposure. Epinephrine was the most common treatment, followed by antihistamines, inhaled beta-agonists, and corticosteroids (108348).
Approximately one-third of patients with IgE-mediated sesame allergy have reported previous use of epinephrine due to this allergy (100501). There is evidence that IgE-mediated sesame allergy is influenced by both genetic and environmental factors; there was a high correlation of the allergy between family members, especially siblings (28175).
Allergens believed to be responsible for sesame seed hypersensitivity include beta-globulin (28213); sesamol, sesamolin, and sesamin (28182,28207); storage proteins including ses i 1 and ses i 2 (2S albumins) (28132,28187,28211,28212,28216,28217), ses i 3 (a 7S vicilin-type globulin) (28187,28214), ses i 4 (28158), ses i 5 (28158), ses i 6 (an 11S globulin) (28132,28215), and ses i 7 (28215). Typically allergens in sesame seeds that cause reactions after oral intake have molecular weights ranging from 8-62 kDa (28208,28210).

Pulmonary/Respiratory ...In clinical trials involving a sesame oil nasal spray, minor adverse effects included adverse smell, oil dripping from the nose, and nasal blockage (27659).

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General ...Orally, no adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.

(Read more about SORGHUM)

General ...Orally and topically, sunflower oil is well tolerated.
Serious Adverse Effects (Rare):
Orally: Allergic reactions in sensitive individuals have been reported.

Immunologic ...Orally, sunflower oil can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. However, the protein content of sunflower oil is very low. In one case report, an allergic response to sunflower oil did not occur despite presenting with severe allergy and anaphylaxis to sunflower seed (108140).

(Read more about SUNFLOWER OIL)

General ...Orally, intramuscularly, and topically, vitamin B12 is generally well-tolerated.
Most Common Adverse Effects:
Intramuscular: Injection site reactions.
Serious Adverse Effects (Rare):
Intramuscularly: Severe hypokalemia has been rarely linked with correction of megaloblastic anemia with vitamin B12.

Cardiovascular ...In human clinical research, an intravenous loading dose of folic acid, vitamin B6, and vitamin B12, followed by daily oral administration after coronary stenting, increased restenosis rates (12150). Hypertension following intravenous administration of hydroxocobalamin has been reported in human research (82870,82864).

Dermatologic ...Orally or intramuscularly, vitamin B12 can cause allergic reactions such as rash, pruritus, erythema, and urticaria. Theoretically, allergic reactions might be caused by the cobalt within the vitamin B12 molecule (82864,90373,90381,103974). In one case report, oral methylcobalamin resulted in contact dermatitis in a 59-year-old Japanese female with a cobalt allergy (103974). In another case report, a 69-year-old female developed a symmetrical erythematous-squamous rash for 5 years after oral vitamin B12 supplementation for 10 years. A patch test confirmed that the systemic allergic dermatitis was due to vitamin B12 supplementation, which resolved 3 months after discontinuation (114578).
Vitamin B12 (intramuscular or oral) has also been associated with at least 19 cases of acneiform eruptions which resolved upon discontinuation of vitamin B12 (90365,90369,90388). High-dose vitamin B12 (20 mcg daily) and vitamin B6 (80 mg daily) have been associated with cases of rosacea fulminans characterized by intense erythema with nodules, papules, and pustules. Symptoms may last up to four months after the supplement is stopped and can be treated with systemic corticosteroids and topical therapy (10998,82870,82871).

Gastrointestinal ...Intravenously, vitamin B12 (hydroxocobalamin) 2. 5-10 grams can cause nausea and dysphagia (82864).

Genitourinary ...Intravenously, vitamin B12 (hydroxocobalamin) 5-15 grams has been associated with chromaturia in clinical research (82870,82871,112282,112264).

Hematologic ...According to case report data, the correction of megaloblastic anemia with vitamin B12 may result in fatal hypokalemia (82914).

Musculoskeletal ...According to case report data, correction of megaloblastic anemia with vitamin B12 has precipitated gout in susceptible individuals (82879).

Neurologic/CNS ...Treatment with vitamin B12 has been rarely associated with involuntary movements in infants with vitamin B12 deficiency (90370,90385,90397). In some cases these adverse reactions were misdiagnosed as seizures or infantile tremor syndrome (90370,90385). These adverse reactions presented 2-5 days after treatment with vitamin B12 and resolved once vitamin B12 was discontinued (90370,90385,90397).

Oncologic ...Although some epidemiological research disagrees (9454), most research has found that elevated plasma levels of vitamin B12 are associated with an increased risk of various types of cancer, including lung and prostate cancers and solid tumors (50411,102383,107743). One study found, when compared with blood levels of vitamin B12 less than 1000 ng/mL, plasma vitamin B12 levels of at least 1000 ng/mL was strongly associated with the occurrence of solid cancer (107743). It is unclear if increased intake of vitamin B12, either through the diet or supplementation, directly affects the risk of cancer. It is possible that having cancer increases the risk of vitamin B12 elevation. However, one observational study has found that the highest quintile of dietary intake of vitamin B12 is associated with a 75% increased incidence of developing esophageal cancer when compared with the lowest quintile in never drinkers, but not drinkers (107147).

Renal ...There is a case report of oxalate nephropathy in a 54-year-old male which was determined to be related to the use of intravenous hydroxocobalamin as treatment for cyanide poisoning. Intermittent hemodialysis was started 5 days after admission, along with a low-oxalate diet, oral calcium acetate, and pyridoxine 5 mg/kg daily (107148). A review of the use of intravenous hydroxocobalamin for suspected cyanide poisoning in 21 intensive care units in France between 2011 and 2017 resulted in a 60% increased odds of acute kidney injury and a 77% increased odds of severe acute kidney injury in the first week. However, biopsies were not conducted and a direct link with use of hydroxocobalamin could not be made (107139).

Other ...Several studies have found that higher vitamin B12 levels may be associated with increased mortality or decreased survival rates in hospitalized elderly patients (82889,82812,82857,82895). Human research has also found a positive correlation between vitamin B12 status and all-cause mortality in Pima Indians with diabetes (82863).

(Read more about VITAMIN B12)