B12 Energy Ginger by MegaFood

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Serving Size 2 Gummy(ies)

Ingredients	Amount Per Serving
Calories	15 Calorie(s)
Total Carbohydrates	3 Gram(s)
Total Sugars	2 Gram(s)
Added Sugars	2 Gram(s)
Vitamin B12 (Methylcobalamin)	24 mcg
organic Ginger (root)	100 mg

Other Ingredients

Tapioca Syrup, Cane Sugar, Apple Pectin, Citric Acid, Sodium Citrate, organic Beet powder PlantPart: root, organic Sunflower Oil, organic Carnauba Wax

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Effectiveness view details

Below is general information about the effectiveness of the known ingredients contained in the product B12 Energy Ginger. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GINGER (organic Ginger)

POSSIBLY EFFECTIVE

Dysmenorrhea. In people with dysmenorrhea, taking oral ginger seems to reduce pain. Clinical research shows that ginger might be comparable to ibuprofen or mefenamic acid. In addition, taking ginger seems to be beneficial when used as an adjunct to mefenamic acid 250 mg twice daily. Details: Clinical research in individuals at least 15 years of age shows that ginger can reduce pain from dysmenorrhea. Clinical studies show that taking ginger powder 500-2000 mg daily usually for the first 3-4 days of a menstrual cycle modestly decreases pain severity by an average of 2.3-2.7 points on a 10-point scale when compared to control groups (89889,89899,91139,91892,96255,106077). However, a meta-analysis of clinical research shows that taking ginger does not reduce pain duration when compared with placebo (106077). Clinical research also shows that ginger might be as effective as some anti-inflammatory agents. Taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily for 3 days at the beginning of the menstrual period or until pain relief improves symptoms similarly to ibuprofen or mefenamic acid (17931,96259,106077). Also, taking a ginger extract 200 mg four times daily for 3-4 days at the beginning of pain is equally effective to taking Novafen, a combination of acetaminophen, caffeine, and ibuprofen (99444). Ginger also seems to improve pain when given as an adjunct to anti-inflammatory agents. A small clinical study in young females with dysmenorrhea shows that adding ginger (Vomigone, Dineh Co.) 500 mg daily to mefenamic acid 250 mg twice daily for 5 days further reduces pain when compared with taking mefenamic acid alone (102464).
Osteoarthritis. Most clinical research shows that taking ginger extract by mouth improves pain in some patients with osteoarthritis. Topical ginger, on the other hand, has not shown benefit for knee osteoarthritis in low quality research. Details: Meta-analyses of clinical research show that taking ginger extract 500-1000 mg daily for 3-12 weeks can modestly improve pain when compared with placebo in some patients with osteoarthritis of the knee or hip (96253,103357). However, a meta-analysis of two clinical studies shows that taking ginger extract about 500 mg daily for 6 weeks does not have an effect on function (103357). Some clinical research has also compared ginger to conventional drug treatment. In one clinical trial, there was no significant difference between ginger extract 30 mg daily and ibuprofen 400 mg three times daily for one month in patients with osteoarthritis of the hip or knee (17930). However, taking a specific ginger extract (Eurovita Extract 33; EV ext-33) orally 170 mg three times daily for 3 weeks was significantly less effective than ibuprofen 400 mg three times daily for reducing pain (7048). Since ginger is thought to take several weeks for significant benefit, this trial might not have lasted long enough. Ginger has also been compared with diclofenac. When used orally as 1500 mg daily in two divided doses, ginger is less effective than oral diclofenac 100 mg daily in two divided doses, or the combination of ginger and diclofenac, for 12 weeks (89898). Various studies have evaluated formulations containing ginger with other ingredients. These combinations have all been shown to improve osteoarthritis pain, and in some cases, functionality. Studied formulations include ginger (Eurovita Extract 35; EV ext-35) 340 mg with glucosamine (Zinaxin glucosamine, Ferrosan AS) 1000 mg daily for 4 weeks, a ginger extract with an alpinia (Alpinia galanga) extract (Eurovita Extract 77; EV ext-77) 255 mg twice daily for 6 weeks, a ginger extract with curcuminoids, and extracts of devil's claw, Boswellia serrata, and celery (Tregocel) for 36 weeks, or Ayurvedic shunthi-guduchi formulations containing ginger, Indian gooseberry, and Tinospora cordifolia, either with or without Boswellia serrata (7084,18210,89557,106078). However, it's too early to know if the effects of these combination agents are associated with ginger or other ingredients in the formulations. Topical ginger, alone or in combination with other ingredients, has also been studied for knee osteoarthritis. Although a meta-analysis of two randomized clinical trials shows no evidence of benefit of topical ginger for pain and disability when compared with placebo or standard therapy (103357), some benefits have been shown in individual preliminary studies (20340,20341,89897,96668,97537,97542). These trials have used a specific gel containing ginger and plai 4% by weight (Plygersic gel, Thailand Institute of Scientific and Technological Research) 4 grams/day in four divided doses for 6 weeks (89897), an ointment composed of ginger, cinnamon, mastic (Saghez), and sesame oil twice daily for 6 weeks (20340), or one gram of ginger extract 5% (standardized to 11.18% of 6-gingerol) in a nanostructure lipid carrier three times daily for up to 12 weeks to the affected knee (96668,97537). Some studies have used ginger essential oil in a massage oil, alone or with sweet orange essential oil or standard therapy, twice weekly for 3 or 6 weeks (20341,97542).
Pregnancy-induced nausea and vomiting. Oral ginger seems to reduce the severity of nausea and vomiting in some people during pregnancy. Ginger seems to be more effective than placebo, comparable to vitamin B6 or dimenhydrinate, and less effective than metoclopramide. Details: Although most clinical studies are small and have methodological limitations, the available research shows that ginger is more effective than placebo, and comparable to vitamin B6 or dimenhydrinate (721,1922,5343,11346,13071,16306,20312,20315,90103,91201,102462). Although ginger is comparable to dimenhydrinate for reducing symptoms of morning sickness, it seems to take about 3 days to reduce vomiting episodes compared to 1 day with dimenhydrinate (16305). In addition, clinical research shows that ginger is less effective than metoclopramide at relieving nausea and vomiting associated with pregnancy (20315). Ginger doses of 500 to 2500 mg daily, divided into two to four daily doses for 3 days to 3 weeks, have been used in clinical research (721,5343,16305,16306,20312,20315,90103,91201). The American College of Obstetrics and Gynecology (ACOG) considers ginger capsules 250 mg 4 times daily a first-line nonpharmacological treatment option for pregnancy-induced nausea based on limited evidence. However, there is no evidence that ginger reduces vomiting (111601).

POSSIBLY INEFFECTIVE

Chemotherapy-induced nausea and vomiting (CINV). Most clinical research shows that oral ginger does not reduce acute or delayed CINV. The effect of ginger might depend on the dose, the other antiemetics used, or the specific chemotherapy regimen. Details: Most clinical research shows that taking ginger as adjunct to adequate antiemetic therapy does not reduce DELAYED CINV when compared with antiemetic therapy alone (20316,96260,89891,96675,97538,97541,101760,102461,113616). Clinical research from meta-analyses and most individual clinical studies also show that taking ginger 0.5-3.5 grams as an adjunct to standard antiemetic therapy does not reduce the incidence or severity of ACUTE CINV when compared with antiemetic therapy alone (89891,96675,101760,102461,102466,113616). However, conflicting results exist from some individual clinical studies (20316,102466). These individual studies evaluated powdered ginger root or liquid extract of ginger root 0.5-2 grams taken in two to four divided doses daily, starting on either the day of or 3 days before chemotherapy and continuing for 3-5 days after chemotherapy initiation (20316,102466). Also, one small study shows that ginger in doses of 1 gram or less for more than 3 days reduces the likelihood of acute vomiting by 60% (101760). More research is needed to confirm the efficacy of this lower dose. Reasons for the conflicting results are unclear, but several theories have been postulated. One theory is that ginger might help reduce CINV associated with some, but not all, chemotherapy regimens. One preliminary clinical study shows that ginger 500 mg twice daily for 3 days reduces vomiting in patients receiving cyclophosphamide and doxorubicin, but not in patients also receiving 5-fluorouracil or docetaxel (96251). However, since there is limited evidence supporting this theory, additional research is needed to confirm. Another theory is that ginger helps when used with certain antiemetic drugs, but not others. For example, ginger seems to help in cases when optimal antiemetic therapy, such as 5-HT3 receptor antagonists, is not available. Small clinical studies show that ginger reduces the severity of acute nausea when compared with prochlorperazine or metoclopramide, both of which are suboptimal antiemetic therapy for CINV (89891). Another small study shows that ginger is comparable to metoclopramide for improving delayed chemotherapy-induced nausea (13244). On the other hand, several studies show that taking ginger 0.5-2 grams daily along with antiemetic therapy that includes aprepitant does NOT improve acute or delayed CINV (20318,89891,96251,96675). In fact, one study found an association between concomitant use of ginger 2 grams daily with aprepitant and worsened severity of delayed nausea. Ginger is hypothesized to decrease the absorption of aprepitant and reduce its effectiveness for delayed nausea (20318,96675). However, this effect has not been replicated, and aprepitant serum levels were not measured to confirm this hypothesis. Finally, many of the studies showing a benefit of ginger for CINV when used as an adjunct to standard antiemetic therapy are considered to be methodologically flawed (20317,96252,96677). For instance, one study using powdered ginger root 1-2 grams daily during the first three days of chemotherapy in children and adults (20317) has been criticized for inaccurately representing data (89891). Other studies of ginger 500 mg twice daily for up to 10 days used questionable methods to measure outcomes and usually did not differentiate between acute and delayed CINV (96252,96677). Ginger essential oil aromatherapy has also been evaluated. One small study shows that using two drops of ginger essential oil on an aromatherapy necklace for 2 minutes daily for 5 days, starting on the first day of chemotherapy, reduces acute nausea, but not vomiting or delayed nausea, when compared with placebo in females with breast cancer taking standard antiemetics including granisetron, dexamethasone, and metoclopramide (96256).
Exercise-induced muscle soreness. Most research shows that oral ginger in single or multiple doses does not prevent or treat exercise-induced muscle soreness. Details: Two small studies in healthy adults show that single doses of ginger supplements do not seem to reduce muscle soreness from exercise. Taking capsules of ground ginger 2 grams, 30 minutes before a 30-minute cycling bout, or 24-48 hours after eccentric exercise, does not reduce muscle pain during exercise or within one hour of ingestion when compared with placebo (17932,17934). Taking multiple doses also does not seem to help. One small study in healthy adults shows that taking capsules with ginger powder 4 grams daily for 5 days before high-intensity eccentric exercise does not reduce muscle soreness over 4 days when compared with placebo (96258). Another small study in healthy adults shows that taking capsules of heated or raw ground ginger 2 grams daily for 8 days prior to eccentric exercise, and continuing supplementation for 3 more days, might modestly reduce muscle soreness 24 hours post-exercise, but not at later time points, when compared with placebo (17933,96258). Ginger has also been tested in combination with other ingredients. One small study in healthy adults shows that taking a specific combination product (ReWin(d), Natural Origins) containing a 4:3 ratio of ginger and annatto powder, 2 grams in divided doses daily for 4 weeks before eccentric exercise and continuing for 3 days after exercise, may modestly reduce muscle pain 48 hours after exercise but not at other time points (105057). This study was funded by the supplement manufacturer.
Motion sickness. Most research shows that oral ginger does not prevent or treat motion sickness. Details: Most clinical research shows that taking ginger 500-1000 mg up to 4 hours prior to travel does not prevent motion sickness (7624,7625,20330,20331). Some patients report subjective feelings of improvement, but in many studies objective measures did not significantly improve (7400). However, one clinical trial suggests that ginger is more effective than dimenhydrinate at reducing gastrointestinal distress associated with motion sickness (20332). Another clinical study seems to show that taking ginger 1-2 grams as a single dose reduces nausea severity and increases the latency before the onset of nausea caused by simulated motion sickness when compared to baseline (20333). The validity of this finding is limited by the lack of a comparator group.

INSUFFICIENT RELIABLE EVIDENCE to RATE

Acute respiratory distress syndrome (ARDS). Some small clinical studies show that giving ginger with tube feeds to hospitalized patients might reduce the duration of serious sequelae from ARDS. Details: A small clinical trial in adults with ARDS shows that administering ginger extract 120 mg in three divided doses daily via nasogastric tubing for 21 days increases the number of ventilator-free days and the amount of feeding tolerated and decreases the number of intensive care unit (ICU) days when compared with placebo. However, it does not seem to improve overall mortality (20343). Also, another small clinical study shows that adding ginger extract 120 mg to tube feeds in three divided doses daily for 8-21 days improves blood oxygen levels by 13% to 20%, as well as the ability of the lungs to expand by 17%, when compared with a coconut oil placebo. The duration of mechanical ventilation and stay in the ICU also improved. However, ginger does not affect other measurements of lung function or physical organ damage in these patients (89886).
Allergic rhinitis (hay fever). It is unclear if oral ginger is beneficial in allergic rhinitis. Details: A small clinical trial shows that taking ginger extract 500 mg daily for 6 weeks is as effective as loratadine 10 mg daily for reducing nasal symptoms of allergic rhinitis (103359).
Antiretroviral-induced nausea and vomiting. Oral ginger seems to improve nausea and vomiting in patients using antiretroviral agents. Details: A small clinical study in patients with HIV shows that taking ginger 0.5 grams twice daily, 30 minutes prior to each dose of antiretroviral for 14 days, reduces the relative likelihood of nausea and vomiting by about 63% and 79%, respectively, when compared with placebo (89887).
Asthma. Although there has been interest in using oral ginger for asthma, there is insufficient reliable information about the clinical effects of ginger for this condition.
Back pain. Although there has been interest in using oral ginger for back pain, there is insufficient reliable information about the clinical effects of ginger for this condition.
Burns. Although there has been interest in using topical ginger for burns, there is insufficient reliable information about the clinical effects of ginger for this condition.
Cancer-related anorexia. It is unclear if oral ginger improves appetite in people with cancer-related anorexia. Details: A small clinical study in patients with cancer-related anorexia and cachexia shows that taking a capsule containing ginger 1650 mg daily for 14 days improves nausea, appetite, reflux, dysmotility, and other gastrointestinal symptoms when compared to baseline (102460). The validity of these findings is limited by the lack of comparator group.
Chronic obstructive pulmonary disease (COPD). Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules of a specific combination product (AKL1, AKL International Ltd.) containing ginkgo extract, ginger, and Picrorhiza kurroa twice daily for 8 weeks does not improve respiratory symptoms when compared with placebo in patients with COPD (89702). Another moderate-sized clinical study in adults with COPD shows that taking a combination product containing extracts of ginger, alpinia, cardamom, cinnamon, and saffron in honey 3 times daily for 8 weeks improves confidence in leaving home and the ratio of forced exploratory volume per second to forced vital capacity of the lungs (FEV1/FVC) when compared with placebo. However, the combination product does not improve most measures of respiratory function or symptoms such as cough, phlegm, chest tightness, dyspnea, reduced energy levels, sleeping disorders, or activity limitations when compared with placebo (111542). It is unclear if these effects are due to ginger, other ingredients, or the combination.
Colic. Although there has been interest in using oral ginger for colic, there is insufficient reliable information about the clinical effects of ginger for this condition.
Constipation. Although there has been interest in using oral ginger for constipation, there is insufficient reliable information about the clinical effects of ginger for this condition.
Coronavirus disease 2019 (COVID-19). It is unclear whether oral ginger is beneficial for patients with COVID-19. Details: Clinical research in adults hospitalized with asymptomatic COVID-19 infection shows that taking ginger 1.5 grams twice daily orally until hospital discharge reduces length of stay from around 8.5 days to 6 days, when compared with placebo. The strongest effect is seen in males over 60 years of age (110005). The relevance of these results is reduced by a lack of blinding, and the fact that the subjects were initially asymptomatic. The efficacy of ginger for treating COVID-19 has also been evaluated in combination with other ingredients. In adults with uncomplicated, moderate COVID-19, taking a combination of ginger, turmeric, ashwagandha, and boswellia (BV-4051, Artovid-20), 1776 mg twice daily orally for 14 days in addition to standard care and starting 48-96 hours after symptom onset, reduces the mean duration of symptoms from about 8 days to 7 days, when compared with placebo (109899). A small open-label study in adults with confirmed mild to moderate COVID-19 shows that taking ginger 1000 mg and ashwagandha 500 mg twice daily for 15 days, along with conventional therapy, leads to a 13.8-fold and 2.6-fold increase in the relative rate of clinical cure at 7 days and 15 days, respectively, when compared with conventional therapy alone. Taking this combination also appears to reduce time to recovery by around 6 days but does not improve the rate of negative COVID-19 tests, chest imaging findings, viral clearance, serum antibodies, or other measures of disease progression when compared with conventional therapy alone (112094). The validity of these findings is limited by a lack of blinding, and the study may have been inadequately powered to detect a difference between groups. Additionally, it is unclear if these effects are due to ginger, ashwagandha, or the combination.
Diabetes. Some preliminary clinical studies suggest that oral ginger might have a small beneficial effect on glycemic control in patients with type 2 diabetes or gestational diabetes. Details: Meta-analyses of several small clinical trials in adults with type 2 diabetes show that taking ginger 1200-3000 mg daily for 8-13 weeks reduces glycated hemoglobin (HbA1c) by around 0.6% to 1% and fasting blood glucose by 19-21 mg/dL when compared with placebo (96680,107898). Additionally, a small clinical study in adults with diabetes on hemodialysis for end stage renal disease shows that taking ginger powder 2000 mg daily for 8 weeks reduces fasting blood glucose and measures of insulin resistance, but not serum insulin levels, when compared with placebo (111543). In patients with gestational diabetes at weeks 24-28 of pregnancy, clinical research shows that taking ginger 1500 mg daily in three divided doses for 6 weeks reduces fasting blood glucose, insulin levels, and measures of insulin resistance by a small amount when compared with placebo, with no effect on postprandial glucose levels (103358).
Diarrhea. Although there has been interest in using oral ginger for various types of diarrhea, including cholera and acute bacterial dysentery, there is insufficient reliable information about the clinical effects of ginger for these conditions.
Dry mouth. It is unclear if rinsing the mouth with ginger extract is beneficial for dry mouth. Details: In patients with dry mouth related to type 2 diabetes, clinical research shows that use of a ginger extract 25% mouthwash 20 mL three times daily for 14 days modestly reduces symptoms of dry mouth when compared with rinsing with a saline control mouthwash (106068). Although this study was indicated as being triple-blind, it is unclear how the taste of ginger was masked.
Dyspepsia. It is unclear if oral ginger is beneficial for dyspepsia. Details: In patients with dyspepsia, a small clinical trial shows that a single dose of ginger root powder 1.2 grams, taken 1 hour prior to eating, does not reduce abdominal discomfort when compared with placebo. However, it increases the rate of gastric emptying (20325).
Erectile dysfunction (ED). It is unclear if oral ginger is beneficial for erectile dysfunction. Details: Preliminary clinical research in middle-aged males with ED shows that taking two capsules of a specific combination product (Revactin, MD Concepts LLC) containing ginger root 250 mg, muira puama 250 mg, guarana 250 mg, and L-citrulline 800 mg twice daily for 3 months improves scores related to erectile function and intercourse satisfaction, but does not improve sexual desire or orgasmic function scores, when compared to baseline (103224). This study is limited by the lack of a placebo control, the use of per-protocol analysis, and a high dropout rate. In fact, 44% of patients withdrew in order to resume use of phosphodiesterase type 5 (PDE5) inhibitors. Further, it is unclear if these effects are due to ginger, other ingredients, or the combination.
Gastroenteritis-associated nausea and vomiting. It is unclear if oral ginger is beneficial for children with gastroenteritis-associated vomiting. Details: In children aged 1-10 years with acute gastroenteritis-associated vomiting, clinical research shows that taking a single dose of ginger reduces the risk of vomiting at least once in the subsequent 8 hours by 20% when compared with placebo. The incidence of vomiting over the next 24 and 48 hours was also modestly reduced. The children were given 20 drops of ginger equivalent to 10 mg immediately, followed by every 8 hours until cessation of vomiting. All children were offered hypotonic oral rehydration solution (ORS) 30 minutes after the first dose (106076). The number of children accepting ORS, and the quantity of ORS consumed, was less in the group receiving placebo. It is unclear if this affected the outcomes of this study. Also, the incidence or severity of nausea was not investigated.
Hangover. It is unclear if oral ginger is beneficial for managing symptoms of hangover. Details: Preliminary clinical research shows that use of a decoction containing a combination of ginger 6 grams, pith of Citrus tangerine 3 grams, and brown sugar decreases symptoms of alcohol hangovers, including nausea, vomiting, and diarrhea, when compared with placebo. The decoction was taken once 5 hours prior to drinking alcohol or four times after drinking alcohol (20320).
Hyperlipidemia. Oral ginger may be modestly beneficial for some patients with hyperlipidemia. Details: A meta-analysis of preliminary clinical research in adults with and without hyperlipidemia shows that taking ginger 200-3000 mg orally daily for 2-24 weeks reduces triglyceride and low-density lipoprotein cholesterol levels by 12 mg/dL and 5 mg/dL, respectively, and increases high-density lipoprotein cholesterol levels by 1 mg/dL when compared with placebo (109521). However, the validity of this study is limited by high heterogeneity. A clinical study in adults with hyperlipidemia shows that taking ginger powder 1 gram three times daily for 45 days reduces triglyceride and cholesterol levels by an additional 36% and 90%, respectively, when compared with placebo (20327).
Hypertension. It is unclear if oral ginger is beneficial for lowering blood pressure. Details: A preliminary clinical study in patients with diabetes and elevated systolic blood pressure shows that drinking black tea containing ginger 3 grams three times daily for 8 weeks does not reduce blood pressure by a clinically significant amount when compared with plain black tea (96669).
Hypothyroidism. It is unclear if oral ginger is beneficial in patients with hypothyroidism. Details: A small clinical study in patients with primary hypothyroidism who are stabilized on thyroid hormone therapy shows that taking ginger powder 500 mg twice daily for 30 days improves symptoms associated with hypothyroidism, including cold intolerance, constipation, dizziness, dry skin, weight gain, and concentration and memory issues, when compared with placebo. However, ginger supplementation does not seem to improve hair loss, hearing, nail fragility, speech, or feelings of depression in these patients (107903).
Insect bite. It is unclear if topical ginger is beneficial for reducing the size of insect bites. Details: Preliminary clinical research shows that a topical application of Trikatu, which contains ginger, long pepper, and black pepper extracts with 0.074% piperine and 0.046% gingerol, does not reduce the papule size associated with mosquito bites when compared with a control compound containing the same base ingredients of camphor 2%, menthol 2%, and eucalyptus oil 4% (89893).
Intraoperative nausea and vomiting (IONV). It is unclear if oral ginger is beneficial for preventing IONV. Details: Clinical research in individuals undergoing elective C-section and receiving cimetidine and metoclopramide, shows that taking ginger 1 gram orally 30 minutes prior to anesthesia reduces the number of episodes of intraoperative nausea, but not vomiting, when compared with placebo (89890). In other clinical research in adults undergoing elective surgical procedures, adding ginger to a high calorie drink consumed pre-operatively reduces the incidence of nausea from 40% to 10%, and the incidence of vomiting from 25% to 10% when compared with the high calorie drink alone (110007). The validity of these results is unclear as only patients were blinded to the treatment group.
Irritable bowel syndrome (IBS). Oral ginger might reduce symptoms of IBS when used in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial shows that taking ginger 1-2 grams daily for 28 days does not improve symptoms or the number of responders when compared with placebo (90102). However, some research shows that ginger might be beneficial in some patients when used along with other herbal ingredients. Taking a capsule containing ginger, boswellia, and yarrow three times daily for 30 days reduces the frequency and severity of abdominal pain, as well as the severity of bloating, when compared with placebo in females, but not males, with mild to moderate IBS (96673). Another clinical study shows that taking an herbal mixture containing ginger, English horsemint, and purple nut sedge tuber three times daily for 8 weeks improves IBS symptoms including abdominal pain, stool frequency, stool consistency, incomplete evacuation, and urgency, when compared to baseline; these improvements are similar to those achieved by taking mebeverine 135 mg three times daily (89900). However, it is unclear if these effects are due to ginger, other ingredients, or the combination.
Joint pain. Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a specific combination product (Instaflex Joint Support, Direct Digital) containing glucosamine sulfate 1500 mg, methylsufonlylmethane 500 mg, white willow bark extract 250 mg, ginger root concentrate 50 mg, Boswellia extract 125 mg, turmeric root extract 50 mg, cayenne 40 m H.U. 50 mg, and hyaluronic acid 4 mg in three divided doses daily for 8 weeks reduces joint pain severity by 37% compared to only 16% with placebo. However, it does not improve joint stiffness or function when compared with placebo (89560). It is unclear if these effects are due to ginger, other ingredients, or the combination.
Menorrhagia. It is unclear if oral ginger is beneficial for menorrhagia. Details: Preliminary clinical research in healthy adults experiencing heavy menstrual bleeding shows that taking ginger 250 mg three times daily for 4 days, starting the day prior to menstruation, and repeating for three menstrual cycles, reduces the amount of menstrual bleeding when compared with placebo (96672).
Menopausal symptoms. Although there has been interest in using oral ginger for menopausal symptoms such as insomnia, there is insufficient reliable information about the clinical effects of ginger for this purpose.
Migraine headache. Small clinical studies suggest that oral ginger may modestly reduce migraine pain severity and duration. However, taking ginger doesn't seem to PREVENT migraines. Details: Ginger does not seem to be effective for the prevention of migraines. Clinical research in patients with episodic migraine shows that taking ginger extract 200 mg three times daily for 3 months does not reduce the number of migraine attacks, the use of analgesics, or the number of days with pain, any more than taking placebo (101761). However, ginger may be beneficial for the treatment of migraine. Clinical research shows that taking ginger extract 400 mg orally in the emergency room along with intravenous ketoprofen 100 mg reduces pain over the next 2 hours when compared with ketoprofen and placebo. This combination also resulted in an overall better response with a higher likelihood of having no or mild pain with treatment (101762). Taking ginger 250 mg at the onset of a common migraine headache seems to be as effective as taking sumatriptan 50 mg for reducing headache severity within two hours of treatment (89894). Furthermore, a combination of ginger and feverfew (GelStat Migraine, GelStat Corporation; LipiGesic M, PuraMed BioScience), administered sublingually at the onset of a migraine attack, decreases the duration and intensity of migraine pain when compared with placebo (19357,22602). It is unclear if these effects are due to ginger, feverfew, or the combination. Feverfew alone has demonstrated some benefit in treating migraines.
Multiple sclerosis (MS). It is unclear if oral ginger is beneficial for MS. Details: A small clinical study in adults with MS shows that taking ginger 500 mg three times daily for 12 weeks reduces disability scores and improves physical and psychological quality of life scores when compared with placebo (111541). Another small clinical study in adults with relapsing-remitting MS shows that taking ginger 500 mg three times daily for 12 weeks reduces the frequency and severity of nausea and constipation and the severity but not frequency of bloating when compared with placebo. However, no improvement was noted in other gastrointestinal symptoms of MS including abdominal pain, anorexia, diarrhea, dysphagia, gas, or heartburn (113614).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral ginger is beneficial for NAFLD. Details: A small clinical study in patients with NAFLD shows that taking ginger 1000 mg twice daily for 12 weeks improves liver steatosis scores but not liver fibrosis scores when compared with placebo. Ginger also modestly improves levels of alanine aminotransferase and gamma-glutamyl transferase but not aspartate aminotransferase (113615). However, it is unclear whether any improvements are clinically significant. Another small clinical study in patients with NAFLD shows that taking ginger root 1500 mg daily for 12 weeks reduces low-density lipoprotein (LDL) cholesterol and fasting blood glucose levels, but does not affect triglycerides, high-density lipoprotein (HDL) cholesterol, insulin resistance, blood pressure, or fatty liver index, when compared with placebo (102465).
Obesity. Oral ginger has primarily been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Although some individual research disagrees (40802), a meta-analysis and most individual clinical trials show that taking ginger alone or with other ingredients does not reduce weight by a clinically significant amount when compared with placebo in overweight or obese individuals (20346,20347,96676,109521). Ginger has been taken alone or in combination with green tea and capsaicin; rhubarb, astragalus, red sage, turmeric, and gallic acid (Number Ten); or raspberry ketone (Razberi K, Integrity Nutraceuticals), caffeine, capsicum extract (Capsimax, OmniActive Health Technologies), bitter orange fruit (Advantra Z, Nutratech Inc), L-theanine, and black pepper fruit extract (Biperine, Sabinsa Corporation) (Prograde Metabolism) (20346,20347,40802,96676). Due to the various other ingredients contained in available formulations, any effect from ginger is unclear.
Parturition. It is unclear if bathing in a ginger bath is beneficial for shortening the duration of labor. Details: Preliminary clinical research shows that bathing in 228 liters of water containing 4 drops of ginger essential oil does not shorten the duration of labor when compared with a regular bath (20345).
Polycystic ovary syndrome (PCOS). It is unclear if oral ginger is beneficial for females with PCOS. Details: Preliminary clinical research in females with PCOS shows that taking ginger 500 mg three times daily orally for 8 weeks decreases body weight, body mass index, and levels of follicle stimulating hormone and luteinizing hormone, when compared with placebo. It does not affect testosterone levels (110006).
Postoperative nausea and vomiting (PONV). Evidence for the use of oral ginger for preventing PONV is inconclusive and conflicting. Reasons for the conflicting findings may relate to the ginger formulation used and the outcomes measured. It is unclear if ginger aromatherapy is beneficial for PONV. Details: Some individual clinical studies, as well as a large, recent meta-analysis of the available clinical research, show that taking ginger by mouth 1 hour prior to surgery does not reduce the incidence of 24-hour PONV (3452,3453,17369,99445). Also, the meta-analysis found that, although ginger reduces the severity of PONV when measured on a visual analogue scale (VAS), it does not reduce the severity of PONV when measured on a verbal descriptive scale (VDS). Furthermore, ginger does not reduce the use of rescue antiemetic medications (99445). However, some small, individual clinical studies and a meta-analysis of older clinical research show that taking ginger by mouth prior to surgery reduces the incidence of 24-hour PONV by up to 16% to 38% (722,723,1919,13237,20336,20338,20339). In addition, large clinical trials show that the frequency and severity of PONV 2-6 hours after surgery are similar when ginger 1 gram is given orally or when medications such as metoclopramide or dexmedetomidine are given intravenously prior to undergoing anesthesia (103356,103360). However, taking ginger prior to general anesthesia, in combination with other antiemetics like dexamethasone or cimetidine and metoclopramide, does not seem to reduce nausea and vomiting when compared with the other medications alone (20337,89890). In contrast, other research shows that powdered ginger 1-2 grams 30-60 minutes before induction of anesthesia has been used in most studies showing benefit, occasionally followed by 1 gram of ginger administered two hours after surgery (722,723,13237,20336,20338,103356,103360). Ginger aromatherapy has also been evaluated for the prevention of PONV. Application of 5% ginger essential oil to the wrists of patients prior to the induction of general anesthesia seems to prevent PONV in approximately 80% of treated patients (20334). Also, use of ginger essential oil aromatherapy on a gauze pad results in nausea relief in approximately 67% of patients compared with 40% in the placebo group; however, a blend of essential oils including ginger, spearmint, peppermint, and cardamom, results in nausea relief in 82% of patients (89888).These conflicting findings may be due to differences in outcome measures and the chemical compositions of ginger preparations used in the various clinical studies. Some evidence suggests that the efficacy of ginger for preventing PONV differs based on the formulation used. A network meta-analysis of 18 studies evaluating various ginger preparations, including ginger oil, ginger powder, ginger extract, and a combination of ginger powder and antiemetics, for the prevention of PONV suggests that ginger powder and ginger oil are the most effective formulations for preventing nausea and vomiting, respectively. The analysis also shows that while no ginger formulation is superior to another for the prevention of nausea, ginger powder and ginger oil have a lower risk of postoperative vomiting when compared with ginger extract. A subgroup analysis suggests that ginger seems to be most effective in adults over 30 years of age, when administered preoperatively, and when used for gastrointestinal, hepatobiliary, obstetric, or ophthalmic surgeries (112108).
Postoperative recovery. It is unclear if oral ginger is beneficial for postoperative recovery. Details: One preliminary clinical study in adults who had a tonsillectomy shows that taking a specific ginger supplement (Solgar, Leonia) 500 mg twice daily for 7 days along with acetaminophen and antibiotics modestly improves pain and wound healing when compared with acetaminophen and antibiotics alone (96674).
Postpartum complications. It is unclear if oral ginger is beneficial in patients with postpartum pain. Details: A small clinical study in patients recovering from vaginal delivery shows that taking ginger powder 500 mg 8-hours post-delivery, followed by 250 mg every 8 hours thereafter for 24 hours, reduces postpartum pain by nearly 1 point on a 10-point rating scale when compared with placebo (107904). It is unclear if this improvement would be considered clinically relevant.
Radiation-induced nausea and vomiting. It is unclear if oral ginger is beneficial in patients with radiation-induced nausea and vomiting. Details: A very small study in adults with cervical cancer undergoing treatment with cisplatin and radiotherapy shows that taking ginger 250-500 mg twice daily for 6 weeks in addition to standard antiemetic therapy does not reduce acute or delayed nausea and vomiting when compared with antiemetic therapy alone (113616).
Rheumatoid arthritis (RA). One small clinical study suggests that oral ginger may improve some symptoms of RA. Details: Preliminary clinical research in adults with RA shows that taking ginger powder 1500 mg daily for 12 weeks improves disease activity on the Disease Activity Score-28 when compared with placebo (100697).
Smoking cessation. Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with a history of smoking 5 or more cigarettes daily for at least 3 years shows that taking a specific combination product containing ginger 25 mg, turmeric, ashwagandha, Indian gooseberry, tribulus, bacopa, Albizia lebbeck, licorice, clove, cowhage, holy basil, and turmeric (Smotect, Smotect India) daily for 3 months reduces the number of cigarettes smoked by approximately 3 per day when compared with placebo. This product also reduces levels of alveolar carbon monoxide and carboxyhemoglobin but does not improve lung capacity (112115). However, only data from patients who completed treatment were analyzed, which limits the validity of this study. It is also unclear if these effects are due to ginger, other ingredients, or the combination.
Swallowing dysfunction. The effects of oral ginger for treating swallowing dysfunction are inconclusive. Reasons for the conflicting findings may relate to the route of administration or the number of treatments provided. Details: Clinical research shows that applying a spray containing ginger and clematix root (Tongyan) to the oropharynx for 28 days is more effective than placebo at treating grade 2 or 3 dysphagia in stroke victims. However, there does not seem to be a beneficial effect in patients with grade 1 dysphagia (20342). Other clinical research in elderly patients with dysphagia shows that taking a single dose of ginger 2 mg orally does not improve swallowing but increases saliva (96671). It is possible that a single dose of ginger is not enough to improve swallowing function.
Toxin-induced liver damage. Oral ginger might help to prevent liver damage in patients using antimycobacterial drugs. Details: Preliminary clinical research shows that a specific ginger supplement (Zintoma, Goldaru) 500 mg taken 30 minutes prior to antimycobacterial drugs daily for 4 weeks reduces the percentage of patients experiencing an increase in liver function enzymes to greater than five times the upper limit of normal by 54% when compared with placebo. Antimycobacterial drugs used for tuberculosis in the study included isoniazid 5 mg/kg, rifampin 10 mg/kg, ethambutol 15 mg/kg, and pyrazinamide 25 mg/kg daily (96670).
Traumatic brain injury (TBI). Oral ginger has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary research in young adults with subjective memory dysfunction associated with mild TBI, shows that taking a combination of ginger 36 mg and boswellia 360 mg (Memoral) every 8 hours orally for one month improves scores for some, but not all, parameters on an auditory-visual learning test performed at one and three months, when compared with placebo. Total learning scores increased by about 7.5 points with the ginger combination product, compared with 4 points for placebo (110132). It is unclear if these effects are due to ginger, boswellia, or the combination.
Ulcerative colitis. It is unclear if oral ginger is beneficial for improving symptoms of ulcerative colitis. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking ginger powder 1000 mg twice daily for 12 weeks improves disease activity as measured by the Simple Clinical Colitis Activity Index Questionnaire when compared with taking placebo. However, taking ginger did not improve quality of life, stool frequency, bowel distress, or flatulence when compared with placebo (100694). It is possible that this study was not adequately powered to detect a difference in these secondary outcomes.
Upper respiratory tract infection (URTI). Although there has been interest in using oral ginger for various upper respiratory tract infections, there is insufficient reliable information about the clinical effects of ginger for this condition.
Vertigo. It is unclear if oral ginger is beneficial for improving symptoms of vertigo. Details: A small clinical study shows that taking 1 gram of ginger orally as a single dose prior to stimulated vertigo seems to reduce symptoms of vertigo, including nausea, when compared with placebo. However, it does not seem to reduce nystagmus (7623). More evidence is needed to rate ginger for these uses.

(Read more about GINGER)

VITAMIN B12

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).
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 (111554).
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).
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.
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.

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Safety view details

Below is general information about the safety of the known ingredients contained in the product B12 Energy Ginger. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GINGER (organic Ginger)

LIKELY SAFE ...when used orally and appropriately. Ginger has been safely used in multiple clinical trials (721,722,723,5343,7048,7084,7085,7400,7623,11346)(12472,13080,13237,13244,17369,17928,17929,89889,89890,89894)(89895,89898,89899,90102,96252,96253,96259,96260,96669) (101760,101761,101762,103359,107903).

POSSIBLY SAFE ...when used topically and appropriately, short-term (89893,89897).

CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Ginger powder has been used with apparent safety at a dose of up to 750 mg daily for 4 days in girls aged 14-18 years (96255).

PREGNANCY: LIKELY SAFE
when consumed in the amounts typically found in foods. Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG) (111601). However, it should not be used long-term or without medical supervision and close monitoring.

PREGNANCY: POSSIBLY SAFE
when used for medicinal purposes. Despite some early reports of adverse effects (721,7083) and one observational study suggesting that taking dried ginger and other herbal supplements during the first 20 weeks of pregnancy marginally increased the chance of stillbirth (96254), most research shows that ginger is unlikely to cause harm to the baby. The risk for major malformations in infants of parents who took ginger when pregnant does not appear to be higher than the baseline rate of 1% to 3% (721,1922,5343,11346,13071,13080,96254). Also, other research suggests that ginger intake during various trimesters does not significantly affect the risk of spontaneous abortion, congenital malformations, stillbirth, perinatal death, preterm birth, low birth weight, or low Apgar scores (18211,90103). Ginger use has been associated with an increase in non-severe vaginal bleeding, including spotting, after week 17 of pregnancy (18211).

LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods. There is insufficient reliable information available about the safety of ginger when used for medicinal purposes; avoid amounts greater than those found in foods.

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VITAMIN B12

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)(111551,111554).

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.

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Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product B12 Energy Ginger. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GINGER (organic Ginger)

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.

Details

Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels (12636,20402,20403,20404,20405,89895,89896,107898).

CALCIUM CHANNEL BLOCKERS

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = D

Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.

Details

Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects (12633). Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone (107901).

CYCLOSPORINE (Neoral, Sandimmune)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.

Details

In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Insignificant • Occurrence = Possible • Level of Evidence = D

Theoretically, ginger might increase the levels of CYP1A2 substrates.

Details

In vitro research shows that ginger inhibits CYP1A2 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Insignificant • Occurrence = Possible • Level of Evidence = D

Theoretically, ginger might increase the levels of CYP2B6 substrates.

Details

In vitro research shows that ginger inhibits CYP2B6 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Insignificant • Occurrence = Possible • Level of Evidence = D

Theoretically, ginger might increase the levels of CYP2C9 substrates.

Details

In vitro research shows that ginger inhibits CYP2C9 activity (111544). However, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Ginger might increase or decrease the levels of CYP3A4 substrates.

Details

In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity (111544,111644). Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans.

LOSARTAN (Cozaar)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, ginger might increase levels of losartan and the risk of hypotension.

Details

In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

METRONIDAZOLE (Flagyl)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, ginger might increase levels of metronidazole.

Details

In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).

NIFEDIPINE (Procardia)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.

Details

Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.

Details

In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates (111544,111644). Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).

PHENPROCOUMON (Marcoumar, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Ginger might increase the risk of bleeding with phenprocoumon.

Details

Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Ginger might increase the risk of bleeding with warfarin.

Details

Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.

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VITAMIN B12

None known.

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Adverse Effects view details

Report an Adverse Reaction to B12 Energy Ginger

Below is general information about the adverse effects of the known ingredients contained in the product B12 Energy Ginger. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

GINGER (organic Ginger)

General ...Orally, ginger is generally well tolerated. However, higher doses of 5 grams per day increase the risk of side effects and reduce tolerability. Topically, ginger seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, burping, diarrhea, heartburn, and a pepper-like irritant effect in the mouth and throat. However, some of these mild symptoms may be reduced by ingesting encapsulated ginger in place of powdered ginger.
Topically: Dermatitis in sensitive individuals.

Cardiovascular ...Orally, use of ginger resulted in mild arrhythmia in one patient in a clinical trial (16306).

Dermatologic ...Orally, ginger can cause hives (17933), as well as bruising and flushing (20316) or rash (20316).
Topically, ginger can cause dermatitis in sensitive individuals (12635,46902).

Gastrointestinal ...Orally, common side effects of ginger include nausea (17933,22602,89898,101761), belching (10380,103359), dry mouth (103359), dry retching (10380), vomiting (10380), burning sensation (10380), oral numbness (22602), abdominal discomfort (5343,89898,96253), heartburn (5343,7624,12472,16306,20316,51845,89894,89895,89898,89899)(101760,101761,101762,111543), diarrhea (5343,101760), constipation (89898,101760,101761), or a transient burning or "chilly hot" sensation of the tongue and throat (52076). Orally, Number Ten, a specific product composed of rhubarb, ginger, astragalus, red sage, and turmeric, can increase the incidence of loose stools (20346).
Four cases of small bowel obstruction due to ginger bolus have been reported following the ingestion of raw ginger without sufficient mastication (chewing). In each case, the bolus was removed by enterotomy. Ginger is composed of cellulose and therefore is resistant to digestion. It can absorb water, which may cause it to swell and become lodged in narrow areas of the digestive tract (52115).

Genitourinary ...In one clinical trial, some patients reported increased menstrual bleeding while taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily orally for 3 days (17931). An "intense" urge to urinate after 30 minutes was reported in two of eight patients given 0.5-1 gram of ginger (7624). However, this effect has not been corroborated elsewhere. Dysuria, flank pain, perineal pain, and urinary stream interruption have been reported in a 43-year-old male who drank ginger tea, containing 2-3 teaspoons of dry ginger, daily over 15 years. The adverse effects persisted for 4 years and were not associated with increases in urinary frequency or urgency. Upon discontinuing ginger, the patient's symptoms began to improve within one week and completely resolved after eight weeks, with no relapses six months later (107902).

Immunologic ...In one case report, a 59-year-old Japanese female with multiple allergic sensitivities developed pruritus and then anaphylactic shock after taking an oral ginger-containing herbal supplement for motion sickness (Keimei Gashinsan, Keimeido). The patient had used this supplement previously for over 20 years with no allergic reaction. The authors theorized the development of a cross-reactivity to ginger after the use of an oral supplement containing zedoary and turmeric, which are also in the Zingiberaceae family (102463).

Neurologic/CNS ...Orally, ginger may cause sedation, drowsiness, or dizziness (16306,17933,51845).

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VITAMIN B12

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 reaction 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 woman with a cobalt allergy (103974). 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).

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).

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