Two capsules contain: Magnesium (as aspartate, citrate, malate) 125 mg • Chromium (as polynicotinate) 100 mcg • Hawthorn leaf extract (1.8-2.2% vitexin) 300 mg • Garlic bulb (10,000 ppm allicin) 200 mg • Grape seed extract (70% phenols) 50 mg • Coleus Forskohlii root extract (8% forskohlin) 156 mg. Other Ingredients: Gelatin, Magnesium Stearate, Silicon Dioxide.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Daily BP Support. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Daily BP Support. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Chromium has been safely used in doses up to 1000 mcg daily for up to 6 months (1934,5039,5040,6858,6859,6860,6861,6862,6867,6868)(7135,7137,10309,13053,14325,14440,17224,90057,90061)(90063,94234,95095,95096,95097,98687); however, most of these studies have used chromium doses in a range of 150-600 mcg. The Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, long-term. Chromium has been safely used in a small number of studies at doses of 200-1000 mcg daily for up to 2 years (7060,7135,42618,42628,42666,110605,110607,110609). However, the Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).
CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts not exceeding the daily adequate intake (AI) levels by age: 0-6 months, 0.
2 mcg; 7-12 months, 5.5 mcg; 1-3 years, 11 mcg; 4-8 years, 15 mcg; males 9-13 years, 25 mcg; males 14-18 years, 35 mcg; females 9-13 years, 21 mcg; females 14-18 years, 24 mcg (7135). POSSIBLY SAFE...when used orally and appropriately in amounts exceeding AI levels. Chromium 400 mcg daily has been used safely for up to 6 weeks (42680).
PREGNANCY: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for pregnancy is 28 mcg daily for those 14-18 years of age and 30 mcg daily for those 19-50 years of age (7135).
PREGNANCY: POSSIBLY SAFE
when used orally in amounts exceeding the adequate intake (AI) levels.
There is some evidence that patients with gestational diabetes can safely use chromium in doses of 4-8 mcg/kg (1953); however, patients should not take chromium supplements during pregnancy without medical supervision.
LACTATION: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels.
The AI for lactation is 44 mcg daily for those 14-18 years of age and 45 mcg daily for those 19-50 years of age (7135). Chromium supplements do not seem to increase normal chromium concentration in human breast milk (1937). There is insufficient reliable information available about the safety of chromium when used in higher amounts while breast-feeding.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Coleus extract 500 mg daily has been used for up to 3 months without significant adverse effects (91885,100851). ...when used intravenously and appropriately, short-term. Intravenous forskolin, a constituent of coleus, seems to be safe when given at an appropriate rate of 0.5 mcg/kg/minute and increased at 15 minute intervals to 1.0, 2.0, and 3.0 mcg/kg/minute up to 1 hour (7278,7279). ...when used by inhalation and appropriately. Single-dose inhalation of forskolin powder 10 mg from a Spinhaler inhalator seems to be safe and well-tolerated (7281). ...when used ophthalmologically and appropriately. Coleus suspension eye drops (1%) have been safely used in clinical studies (7282,7283,7284,7402,7403,7405).
POSSIBLY UNSAFE ...when used orally in higher doses. Although coleus extracts have been used with apparent safety in doses up to 1.4 grams daily for 2 months (91884), taking coleus extract in doses exceeding 500 mg daily has been associated with an increased incidence of adverse effects, which are primarily gastrointestinal (100851).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Evidence from animal research suggests that high doses of coleus can inhibit embryo implantation and/or delay fetal development (25174); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Garlic has been used safely in clinical studies lasting up to 7 years without reports of significant toxicity (1873,4782,4783,4784,4785,4786,4787,4789,4790,4797)(4798,6457,6897,14447,96008,96009,96014,102016,102670,103479)(107238,107239,107352,108607,110722,111763,114892).
POSSIBLY SAFE ...when used topically. Garlic-containing gels, lipid-soluble garlic extracts, garlic pastes, and garlic mouthwashes have been safely used in clinical research for up to 3 months (4766,4767,8019,15030,51330,51386). ...when used intravaginally. A vaginal cream containing garlic and thyme has been safely used nightly for 7 nights (88387).
POSSIBLY UNSAFE ...when raw garlic is used topically (585). Raw garlic might cause severe skin irritation when applied topically.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Garlic is reported to have abortifacient activity (11020). One study also suggests that garlic constituents are distributed to the amniotic fluid after a single dose of garlic (4828). However, there are no published reports of garlic adversely affecting pregnancy. In clinical research, garlic 800 mg daily was used during the third trimester of pregnancy with no reported adverse outcomes (9201,51626). There is insufficient reliable information available about the safety of topical garlic during pregnancy.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (3319).
LACTATION: POSSIBLY UNSAFE
when used orally in amounts greater than those found in foods.
Several small studies suggest that garlic constituents are secreted in breast milk, and that nursing infants of mothers consuming garlic are prone to extended nursing (3319,4829,4830). There is insufficient reliable information available about the safety of topical garlic during lactation.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately for up to 8 weeks.
Garlic extract 300 mg three times daily has been used with apparent safety for up 8 weeks in children ages 8-18 years (4796). There is insufficient reliable information available about the safety of garlic when used over longer durations or in higher doses.
CHILDREN: POSSIBLY UNSAFE
when raw garlic is used topically.
Raw garlic might cause severe skin irritation when applied topically (585,51210).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).
POSSIBLY SAFE ...when the whole fruit of the grape, or extracts of the fruit, seed, or leaf, are used orally and appropriately in medicinal amounts. Grape seed extracts have been used with apparent safety in doses up to 200 mg daily for up to 11 months (9182,53016) and in doses up to 2000 mg daily for up to 3 months (53149,53190). Specific grape fruit extracts (Stilvid, Actafarma; Cognigrape, Bionap srl) have been used with apparent safety in doses up to 250-350 mg daily for 3-12 months or 700 mg daily for 6 months (53254,53256,96198). A specific grape leaf extract (AS 195, Antistax, Boehringer Ingelheim) has been used with apparent safety in doses up to 720 mg daily for up to 3 months (2538,52985,53005,53206). A preparation of dehydrated whole grapes, equivalent to 250 grams of fresh grapes daily, has also been used with apparent safety for up to 30 days (18228). A specific grape seed extract (Enovita; Indena SpA) 150 mg twice daily, standardized to provide at least 95% oligomeric proanthocyanins, has been used with apparent safety for up to 16 weeks (108091) ...when used topically and appropriately. Creams and ointments containing grape seed extract 2% or 5% have been used topically with apparent safety for up to 3 weeks (91539,100955). There is insufficient reliable information available about the safety of other grape plant parts when used topically.
CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods.
Grapes and grape skin extracts have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). However, whole grapes should be eaten with caution in children aged 5 years and under. Whole grapes can be a choking hazard for young children (96193). To reduce the risk of choking, whole grapes should be cut in half or quartered before being given to children. There is insufficient reliable information available about the safety of grape when used in medicinal amounts in children.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods.
There is insufficient reliable information available about the safety of medicinal amounts during pregnancy and breast-feeding; avoid using in amounts greater than what is commonly found in foods.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Hawthorn preparations in doses of up to 1800 mg daily seem to be safe when used for up to 16 weeks. Although hawthorn might be safe for long-term use, current studies have not evaluated safety past 16 weeks (8279,8280,8281,10144,17203,104689). There is insufficient reliable information available about the safety of hawthorn when used topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Oral magnesium is safe when used in doses below the tolerable upper intake level (UL) of 350 mg daily (7555). ...when used parenterally and appropriately. Parenteral magnesium sulfate is an FDA-approved prescription product (96484).
POSSIBLY UNSAFE ...when used orally in excessive doses. Doses greater than the tolerable upper intake level (UL) of 350 mg daily frequently cause loose stools and diarrhea (7555).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Magnesium is safe when used in doses below the tolerable upper intake level (UL) of 65 mg daily for children 1 to 3 years, 110 mg daily for children 4 to 8 years, and 350 mg daily for children older than 8 years (7555,89396). ...when used parenterally and appropriately (96483).
CHILDREN: LIKELY UNSAFE
when used orally in excessive doses.
Tell patients not to use doses above the tolerable upper intake level (UL). Higher doses can cause diarrhea and symptomatic hypermagnesemia including hypotension, nausea, vomiting, and bradycardia (7555,8095).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Magnesium is safe for those pregnant and breast-feeding when used in doses below the tolerable upper intake level (UL) of 350 mg daily (7555).
PREGNANCY AND LACTATION: POSSIBLY SAFE
when prescription magnesium sulfate is given intramuscularly and intravenously prior to delivery for up to 5 days (12592,89397,99354,99355).
However, due to potential adverse effects associated with intravenous and intramuscular magnesium, use during pregnancy is limited to patients with specific conditions such as severe pre-eclampsia or eclampsia. There is some evidence that intravenous magnesium can increase fetal mortality and adversely affect neurological and skeletal development (12590,12593,60818,99354,99355). However, a more recent analysis of clinical research shows that increased risk of fetal mortality seems to occur only in the studies where antenatal magnesium is used for tocolysis and not for fetal neuroprotection or pre-eclampsia/eclampsia (102457). Furthermore, antenatal magnesium does not seem to be associated with increased risk of necrotizing enterocolitis in preterm infants (104396). There is also concern that magnesium increases the risk of maternal adverse events. A meta-analysis of clinical research shows that magnesium sulfate might increase the risk of maternal adverse events, especially in Hispanic mothers compared to other racial and ethnic groups (60971,99319).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Tell patients to avoid exceeding the tolerable upper intake level (UL) of 350 mg daily. Taking magnesium orally in higher doses can cause diarrhea (7555). ...when prescription magnesium sulfate is given intramuscularly and intravenously prior to delivery for longer than 5 days (12592,89397,99354,99355). Maternal exposure to magnesium for longer than 5-7 days is associated with an increase in neonatal bone abnormalities such as osteopenia and fractures. The U.S. Food and Drug Administration (FDA) recommends that magnesium injection not be given for longer than 5-7 days (12590,12593,60818,99354,99355).
Below is general information about the interactions of the known ingredients contained in the product Daily BP Support. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
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Theoretically, aspirin might increase chromium absorption.
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Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood (21055).
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Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
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Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
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Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone (16012). Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.
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NSAIDs might increase chromium levels in the body.
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Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention (7135).
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Theoretically, concomitant use of coleus and anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.
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Theoretically, combining coleus with antihypertensive drugs might cause additive blood pressure lowering effects and increase the risk of hypotension.
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Theoretically, combining coleus with calcium channel blockers might increase the coronary vasodilatory effects.
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Theoretically, taking coleus may affect drugs metabolized by CYP2C9 and increase the risk of adverse effects or reduce the effectiveness.
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Research on the effect of coleus on CYP2C9 is conflicting. Some animal research shows that coleus extract can induce CYP2C9, while in vitro research shows that coleus can inhibit CYP2C9 (91891). Until more is known, advise patients that taking coleus might increase or decrease levels of drugs metabolized by CYP2C9.
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Theoretically, taking coleus might decrease serum levels of drugs metabolized by CYP3A4.
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In vitro research shows that coleus can activate the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4 (44399,44412). Although the clinical significance of this is not known, use caution when considering concomitant use of coleus and other drugs affected by these enzymes.
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Theoretically, combining coleus with nitrates might increase the coronary vasodilatory effects.
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Theoretically, taking coleus may affect the metabolism of warfarin and increase the risk of adverse effects or reduce the effectiveness.
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Some animal research shows that coleus extract can induce cytochrome P450 2C9 (CYP2C9), an enzyme that metabolizes warfarin. However, other in vitro research shows that coleus can inhibit CYP2C9 (91891). Theoretically, taking coleus with drugs metabolized by CYP2C9 might affect drug levels and the risk of adverse effects. Until more is known, advise patients that taking coleus might increase or decrease levels of warfarin.
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Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, garlic might decrease levels and effects of atazanavir.
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In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4) (88388). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.
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Garlic might increase levels of drugs metabolized by CYP2E1.
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Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39% (10847). Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.
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Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
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Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa (7027,93578). Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels (17221). Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days (96010). Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic might decrease levels of isoniazid.
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Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa (15031); however, the exact mechanism of this potential interaction is not known.
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Theoretically, garlic products containing allicin might decrease levels of PIs.
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Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa (7027,93578). Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506).
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Theoretically, garlic containing allicin might decrease levels of saquinavir.
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Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa (7027,93578). Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin (10335,10847,15031,94506). Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.
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Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.
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Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic (109524).
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Theoretically, garlic might increase levels of tacrolimus.
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In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus (96010).
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Theoretically, garlic might increase the risk of bleeding with warfarin.
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Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time (586,616,1874,3234,4366,4802,4803,51397). In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use (51228,51631). However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk (15032,16416). More evidence is needed to determine the safety of using garlic with warfarin.
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Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
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A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water (53177). Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.
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Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
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A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2 (2539).
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It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
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In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes (11094,53011,53089). However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism (11094). The effects of continued grape juice consumption are unclear.
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Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
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In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes (53011). However, this interaction has not been reported in humans.
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Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
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In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes (52949). However, this interaction has not been reported in humans.
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It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
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Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
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Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination (53011).
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Grape juice might decrease phenacetin absorption.
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A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2) (2539).
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Theoretically, hawthorn may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In vitro and animal research shows that hawthorn can inhibit platelet aggregation (95528,95529,95530,95531). However, its effect in humans is unclear. One observational study shows that patients taking hawthorn shortly before undergoing coronary artery bypass graft (CABG) surgery or valve replacement surgery have a 10% incidence of postoperative bleeding, compared with 1% in those who never consumed hawthorn extract (95527). However, clinical research shows that taking a specific preparation of dried hawthorn leaves and flowers (Crataesor, Soria Natural Lab) 800 mg three times daily for 15 days does not affect platelet aggregation or levels of thromboxane B2, the metabolite of thromboxane A2, in healthy humans (54664).
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Theoretically, concomitant use might cause additive effects on blood pressure and heart rate.
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Theoretically, concomitant use might cause additive coronary vasodilation and hypotensive effects.
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Theoretically, hawthorn might potentiate the effects and adverse effects of digoxin.
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Hawthorn appears to improve cardiac output (12595); however, hawthorn does not appear to affect digoxin pharmacokinetics (19249). Case reports suggest that at least one species of hawthorn root extract (Crataegus mexicana) may produce adverse effects similar to digoxin and can cross-react with digoxin assays, leading to falsely elevated plasma digoxin levels (113112,113113).
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Theoretically, concomitant use might cause additive coronary vasodilatory effects.
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Theoretically, concomitant use might result in additive vasodilation and hypotension.
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Hawthorn might inhibit PDE-5 and cause vasodilation (12595).
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Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
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Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously (13362).
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Use of acid reducers may reduce the laxative effect of magnesium oxide.
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A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect (90033). This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.
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Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
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In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations (20304,20305). Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity (20306). However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur (60759).
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Magnesium can decrease absorption of bisphosphonates.
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Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours (13363).
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Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
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Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium (3046,20264,20265,20266), although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness (60831). High doses of magnesium could theoretically have additive effects with other calcium channel blockers.
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Magnesium salts may reduce absorption of digoxin.
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Gabapentin absorption can be decreased by magnesium.
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Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43% (90032). Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.
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Magnesium might precipitate ketamine toxicity.
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In one case report, a 62-year-old hospice patient with terminal cancer who had been stabilized on sublingual ketamine 150 mg four times daily experienced severe ketamine toxicity lasting for 2 hours after taking a maintenance dose of ketamine following an infusion of magnesium sulfate 2 grams (105078). Since both magnesium and ketamine block the NMDA receptor, magnesium is thought to have potentiated the effects of ketamine.
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Magnesium can reduce the bioavailability of levodopa/carbidopa.
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Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa (100265).
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Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
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Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics (9613,9614,9622). Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.
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Magnesium decreases absorption of quinolones.
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Magnesium can form insoluble complexes with quinolones and decrease their absorption (3046). Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.
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Sevelamer may increase serum magnesium levels.
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In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear (96486).
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Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Details
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes (3046,97492,107364). Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate (107364). A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg) (96485). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg (107364). Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time (112781,112782). It does not affect the activity of subsequently administered neostigmine (112782).
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Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Details
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone (20307). A similar interaction occurs between magnesium hydroxide and glipizide (20308). The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas (22364).
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Magnesium decreases absorption of tetracyclines.
Details
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity (12586). Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.
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Below is general information about the adverse effects of the known ingredients contained in the product Daily BP Support. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, chromium is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal irritation, headaches, insomnia, irritability, mood changes.
Serious Adverse Effects (Rare):
Orally: Rare cases of kidney and liver damage, rhabdomyolysis, and thrombocytopenia have been reported.
Dermatologic
...Orally, chromium-containing supplements may cause acute generalized exanthematous pustulosis (42561), skin rashes (42679), and urticaria (17224).
Also, chromium picolinate or chromium chloride may cause systemic contact dermatitis when taken orally, especially in patients with contact allergy to chromium (6624,90058). In one clinical study, a patient taking chromium nicotinate 50 mcg daily reported itchy palms that improved after the intervention was discontinued. It is unclear of this effect was due to the chromium or another factor (95096).
Topically, hexavalent chromium, which can be present in some cement, leather products, or contaminated soil, may cause allergic contact dermatitis (42645,42789,90060,90064,110606).
A case of lichen planus has been reported for a patient following long-term occupational exposure to chromium (42688).
Endocrine ...Orally, cases of hypoglycemia have been reported for patients taking chromium picolinate 200-1000 mcg daily alone or 200-300 mcg two or three times weekly in combination with insulin (42672,42783). Chromium picolinate has also been associated with weight gain in young females who do not exercise and in those following a weight-lifting program (1938).
Gastrointestinal
...Orally, chromium in the form of chromium picolinate, chromium polynicotinate, chromium-containing brewer's yeast, or chromium-containing milk powder may cause nausea, vomiting, diarrhea, decreased appetite, constipation, flatulence, or gastrointestinal upset (14325,42594,42607,42622,42643,42679).
Long-term exposure to heavy metals, including chromium, has been associated with increased risk of gallbladder disease and cancer (42682,42704).
Genitourinary ...Orally, chromium polynicotinate has been associated with disrupted menstrual cycles in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Hematologic ...Anemia, hemolysis, and thrombocytopenia were reported in a 33 year-old female taking chromium picolinate 1200-2400 mcg daily for 4-5 months (554). The patient received supportive care, blood product transfusions, and hemodialysis and was stabilized and discharged a few days later. Lab values were normal at a one-year follow-up.
Hepatic ...Liver damage has been reported for a 33-year-old female taking chromium picolinate 1200 mcg daily for 4-5 months (554). Also, acute hepatitis has been reported in a patient taking chromium polynicotinate 200 mcg daily for 5 months (9141). Symptoms resolved when the product was discontinued. Two cases of hepatotoxicity have been reported in patients who took a specific combination product (Hydroxycut), which also contained chromium polynicotinate in addition to several herbs (13037).
Musculoskeletal ...Acute rhabdomyolysis has been reported for a previously healthy 24-year-old female who ingested chromium picolinate 1200 mcg over a 48-hour time period (42786). Also, chromium polynicotinate has been associated with leg pain and paresthesia in patients taking the supplement to prevent weight gain during smoking cessation (42643).
Neurologic/CNS ...Orally, chromium picolinate may cause headache, paresthesia, insomnia, dizziness, and vertigo (6860,10309,14325,42594). Vague cognitive symptoms, slowed thought processes, and difficulty driving occurred on three separate occasions in a healthy 35-year-old male after oral intake of chromium picolinate 200-400 mcg (42751). Transient increases in dreaming have been reported in three patients with dysthymia treated with chromium picolinate in combination with sertraline (2659). A specific combination product (Hydroxycut) containing chromium, caffeine, and ephedra has been associated with seizures (10307). But the most likely causative agent in this case is ephedra.
Psychiatric ...Orally, chromium picolinate has been associated with irritability and mood changes in patients taking the supplement to lose weight, while chromium polynicotinate has been associated with agitation and mood changes in patients taking the supplement to prevent weight gain during smoking cessation (6860,42643).
Renal
...Orally, chromium picolinate has been associated with at least one report of chronic interstitial nephritis and two reports of acute tubular necrosis (554,1951,14312).
Laboratory evidence suggests that chromium does not cause kidney tissue damage even after long-term, high-dose exposure (7135); however, patient- or product-specific factors could potentially increase the risk of chromium-related kidney damage. More evidence is needed to determine what role, if any, chromium has in potentially causing kidney damage.
Intravenously, chromium is associated with decreased glomerular filtration rate (GFR) in children who receive long-term chromium-containing total parenteral nutrition - TPN (11787).
Topically, burns caused by chromic acid, a hexavalent form of chromium, have been associated with acute chromium poisoning with acute renal failure (42699). Early excision of affected skin and dialysis are performed to prevent systemic toxicity.
Other ...Another form of chromium, called hexavalent chromium, is unsafe. This type of chromium is a by-product of some manufacturing processes. Chronic exposure can cause liver, kidney, or cardiac failure, pulmonary complications, anemia, and hemolysis (9141,11786,42572,42573,42699). Occupational inhalation of hexavalent chromium can cause ulceration of the nasal mucosa and perforation of the nasal septum, and has been associated with pneumoconiosis, allergic asthma, cough, shortness of breath, wheezing, and increased susceptibility to respiratory tract cancer and even stomach and germ cell cancers (42572,42573,42601,42610,42636,42667,42648,42601,42788,90056,90066). Although rare, cases of interstitial pneumonia associated with chromium inhalation have been reported. Symptoms resolved with corticosteroid treatment (42614).
General
...Orally, intravenously, ophthalmologically, and by inhalation, coleus seems to be well tolerated.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, nausea, vomiting.
Intravenously: Flushing, hypotension, tachycardia.
Ophthalmologically: Conjunctival hyperemia, stinging eyes.
Inhalation: Irritation of the respiratory tract, restlessness, tremor.
Cardiovascular ...Intravenously, the coleus constituent, forskolin, can cause tachycardia, flushing and hypotension (7279,44424,44431).
Dermatologic ...Two cases of contact dermatitis have been reported following airborne exposure to coleus (44426,44418).
Gastrointestinal ...Orally, coleus can cause dose-related diarrhea and other gastrointestinal symptoms. Increased bowel movements and loose stools have been reported in 1 of 15 patients taking coleus extract in a clinical trial (91885). Some retrospective evidence reports about a 10% rate of gastrointestinal adverse effects from oral coleus use; 81% of these adverse effects were related to diarrhea. Other reported adverse effects which occurred at a much lower rate, include nausea, vomiting, and/or constipation. Gastrointestinal effects appear to be dose-related; those taking less than 250 mg of coleus extract did not report any diarrhea, while all patients taking 1000 mg of coleus extract reported diarrhea (100851).
Neurologic/CNS ...Inhalation of forskolin, a constituent of coleus, can cause tremor and restlessness (7281).
Ocular/Otic ...Ophthalmologically, forskolin, a constituent of coleus, can cause stinging of the eyes and conjunctival hyperemia (7283).
Pulmonary/Respiratory ...Inhalation of forskolin, a constituent of coleus, can cause throat and upper respiratory tract irritation, and mild to moderate cough (7281).
General
...Orally, garlic is generally well tolerated.
Topically, garlic seems to be well tolerated. Intravenously, there is insufficient reliable information available about adverse effects.
Most Common Adverse Effects:
Orally: Abdominal pain, body odor, flatulence, malodorous breath, and nausea. Allergic reactions in sensitive individuals.
Topically: Burns and dermatitis with fresh garlic.
Serious Adverse Effects (Rare):
Orally: Some case reports raise concerns about increased risk of bleeding with garlic.
Dermatologic
...Orally, garlic may cause pruritus (51316,51474,107239), flushing, and acne (107239).
Oral intake of a specific garlic product containing allicin (Allimax) has been associated with a case of pruritic rash (51474). Enteric-coated garlic tablets standardized to 1.5% allicin have also been associated with a case of pruritus (51316). Garlic has also been associated with a case of superficial pemphigus in a 49-year-old male with type 2 diabetes (51564). Garlic-induced oral ulcers have also been reported (51467).
Topically, garlic may cause contact dermatitis and urticaria (4833,5004,12635,51258,51265,51375,51403,51412,51459,51483)(51511,51512,51530,51616,51617,51618,111769), as well as contact cheilitis (51384). Fresh garlic may be more likely to elicit a reaction than garlic extract. Most reactions have resolved following withdrawal of garlic therapy. In one case report, applying crushed garlic on the neck to help ease a sore throat resulted in an itchy, burning, erythematous lesion in a young female patient. The lesion healed after one week of treatment with topical antibiotics, steroids, and antihistamine ointments (88390). Cases of occupational eczema or dermatitis have been reported in cooks (51303,51210), food handlers (51292), and caterers (51304). According to one case report, dermatitis appeared in chefs exposed to garlic (15033). Treatment with acitretin 25 mg daily or topical psoralen-ultraviolet A (PUVA) for 12 weeks proved effective in mitigating the symptoms. A 34-year-old female with a history of hand dermatitis and paronychia had a worsening of these conditions after peeling raw garlic. She had a positive skin patch test to fresh, raw garlic but not to any other tested allergens, and the conditions resolved when she avoided contact with garlic (105528). Topically, garlic may also cause chemical burns, usually within 12 hours of application. Second- and third-degree chemical burns have been reported in adults, children, and infants exposed to topical garlic, often as an unintended consequence of using garlic medicinally on the skin (585,4832,51226,51230,51252,51281,51377,51418,51468,51495,51536)(51558,51576,51577,88409,96006). A case of painful blisters on the soles of the feet of a 23-year-old Chinese female has been attributed to chemical burns caused by applying crushed raw garlic for 3 hours (51440). Topically, garlic may also cause hyperpigmentation, ulcers, necrotic lesions, facial flushing, and local irritation (4832,15030,51268,51269,108606). In one case report, applying crushed raw garlic to the palatal mucosa for several minutes to relieve mouth pain resulted in a chemical burn that produced a 3 cm necrotic ulcer in an adult female with trigeminal neuralgia (108606).
Gastrointestinal
...Orally, dehydrated garlic preparations or raw garlic may cause malodorous breath (51438,51444), body odor (732,1873,4784,4793,4795,4798,9201,10787,42692,49769)(51269,51316,51467,51602), abdominal pain or fullness, anorexia, diarrhea, constipation, flatulence, belching, heartburn, nausea, unpleasant taste, reflux, and bowel obstruction (1884,6457,6897,9201,49769,51269,51343,51380,51438,51442)(51450,51457,51466,51471,51474,51520,51593,51602,51623,88398)(88405,111766,114892).
Large quantities of garlic may damage the gastrointestinal tract. In one case report, a patient taking garlic for hypertension reported odynophagia and retrosternal pain after taking garlic without any water the previous day. An esophageal lesion 3 cm in length was detected upon endoscopy. The symptoms resolved 3 days after starting a liquid diet and taking lansoprazole 30 mg twice daily and sucralfate four times daily (88389). One case of bowel obstruction was reported in a 66-year-old male who ingested an entire garlic bulb (51525). Esophageal perforation has been reported in at least 17 individuals who consumed entire garlic cloves. In one case the perforation led to mediastinitis and death (102672).
Garlic has also been associated with eosinophilic infiltration of the gastrointestinal tract. In one case report a 42-year-old female presented with symptoms of eosinophilic gastroenteritis, which included pollinosis, asthma, diarrhea, heart burn, peripheral eosinophilia, and urticaria. After stopping use of garlic and sesame, the patient improved (51441). In a case report of eosinophilic esophagitis, garlic was determined to be the causative agent in a patient with long-standing gastrointestinal symptoms. The patient had attempted to treat upper gastrointestinal symptoms as gastrointestinal reflux disease without success for many years. Skin prick testing showed a positive reaction to garlic, of which the patient noted frequent consumption. Marked symptom improvement was noted within 3 weeks of garlic avoidance (88393).
Intravenously, garlic 1 mg/kg of body weight daily diluted into 500 mL saline and administered over 4 hours has been reported to cause abdominal discomfort, vomiting, diarrhea, nausea, anorexia, flatulence, weight loss, and garlicky body odor (51462).
Clinical research suggests that patients with metabolic syndrome taking 1600 mg of powdered garlic by mouth daily for 3 months may experience improved intestinal transit time when compared with placebo, suggesting that garlic powder may reduce symptoms of constipation (110722).
Genitourinary ...Orally, garlic might cause dysuria, hematuria, or polyuria (51438,51450,51467,113618). In one case, an older male with high dietary and supplemental garlic intake at doses of 300-5400 mg daily for 3-4 years developed severe hematuria with clots after undergoing a minimally invasive prostate procedure (113618).
Hematologic
...Oral use of dietary garlic or supplements containing garlic has caused platelet dysfunction, increased fibrinolytic activity, prolonged bleeding time, retrobulbar hemorrhage (bleeding behind the eye) postoperative bleeding, and spinal epidural hematoma (586,587,4801,4802,11325,51397,51473,51491,51532,51534)(51570,51584,51593,51594,113618).
Also, a case of kidney hematoma following extracorporeal shock-wave lithotripsy (SWL) has been reported in a patient with nephrolithiasis who took aged garlic (51630). A case of increased bleeding time that complicated epistaxis management has been reported in a patient taking garlic, aspirin, and milk thistle (51426).
Intravenously, garlic has been associated with the development of thrombophlebitis at the injection site (51462).
Immunologic
...There is a case report of an immediate sensitivity reaction to oral raw garlic, resulting in wheals, in a 31-year-old female.
The patient did not react to cooked garlic, and skin prick tests showed allergy only to raw garlic (96015). Researchers note that at least some allergens in raw garlic are heat labile (88392,96012,96015). This suggests that consuming cooked rather than raw garlic may help avoid this reaction in patients allergic to raw garlic. However, different people react to different allergens in garlic. At least some of these allergens are heat stable (96012). While rare, garlic-induced anaphylaxis has been reported (88392,96012).
Topically, allergic contact dermatitis has been reported in case reports (51406,51498,51510,51519,51560).
Musculoskeletal ...Orally, garlic has been associated with individual cases of gout and low back pain (51474,51467), but it is not clear if these adverse events can be attributed to garlic.
Neurologic/CNS ...Orally, dizziness, insomnia, headaches, diaphoresis, fever, chills, somnolence, increased appetite, euphoria, and weight loss have been reported with garlic (15032,42692,51316,51467,51471,51520). In one case, the smell of garlic was identified as a trigger for migraines in a 32-year-old female. The subject reported fortification spectra along with visual spots for a few seconds followed by instantaneous biparietal, crushing level (10/10) headaches upon exposure to the scent of garlic or onion (88404).
Pulmonary/Respiratory ...Garlic exposure, most notably in occupational settings, may cause asthma and other symptoms such as sneezing, nasal obstruction, rhinorrhea, and sinusitis (40661,51218). A case of minor hemoptysis has been reported for one patient with cystic fibrosis following intake of garlic capsules orally once daily for 8 weeks (51438). A 77-year-old female developed pneumonia related to the intake of one whole black garlic clove daily. The cloves were prepared by heating a whole garlic bulb in a pot for one month. Symptoms included dyspnea and coughing, and test results were positive for lymphocyte-induced stimulation by black garlic and raw garlic. The patient required treatment with oral steroids and was told to avoid garlic (96011).
General
...Orally, the whole fruit, as well as the seed, fruit, and leaf extracts, seem to be well tolerated.
Topically, grape seed extracts seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, dry mouth, dyspepsia, headache, joint pain, and nausea.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis to grape skin has been reported.
Dermatologic ...Orally, mild hair thinning has been reported in a patient taking a specific grape leaf extract AS195 KG) (2538). Urticaria (hives) has also been reported with this same extract (53206). Cases of contact dermatitis have been reported in grape workers, including those working in California vineyards (53270,53272,53275).
Gastrointestinal ...Orally, abdominal pain and nausea have been reported with use of grape seed extract, but these effects typically occur at rates similar to placebo (9182,13162). In a case report of a 57-year-old man, intermittent nausea, vomiting, and diarrhea occurred over a 10-day period and improved once grape seed extract was stopped (96764). Gastrointestinal adverse effects have also been reported with use of a different grape seed extract (Entelon, Hanlim Pharm). However, the specific types of gastrointestinal effects were not described (100954). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused flatulence, mild constipation, gastrointestinal discomfort, diarrhea, dyspepsia, dry mouth, and retching (2538,52985,53206). Diarrhea, gastrointestinal distress, indigestion, and aversion to taste have been reported with use of Concord grape juice (52972,53166,53175,53181,53199). Loose stools have been reported in a clinical trial of grape pomace (99270). Bowel obstruction caused by intact grapes and grape seeds has been described in case reports (53241,53284,53278). Excessive consumption of grapes, dried grapes, raisins, or sultanas might cause diarrhea due to laxative effects (4201).
Hematologic ...Orally, one case of leg hematoma following a minor trauma was reported in a person using grape leaf extract (2538). Also, one case of bruising was reported in a person drinking Concord grape juice daily for 2 weeks (52972).
Immunologic ...Orally, there is one report of an anaphylactic reaction to oral grape skin extract, which included urticaria and angioedema (4073).
Musculoskeletal ...Orally, musculoskeletal disorders, including back pain, have been reported with use of a specific grape leaf extract AS195 KG) (2538,53206). Joint pain and lumbago have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (91541).
Neurologic/CNS ...Orally, headache has been reported with use of grape seed extract, but this effect occurs at rates similar to placebo (9182,91541). A specific grape leaf extract AS195 (Antistax, Boehringer Ingelheim Pharma GmbH & Co. KG) has reportedly caused dizziness, tiredness, headache, and sleep problems (2538,53206). As a class, nervous system adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of adverse neurologic effects were not described (100954).
Ocular/Otic ...Orally, ocular adverse effects have been reported with use of a specific grape seed extract (Entelon, Hanlim Pharm). However, the specific types of ocular adverse effects were not described (100954).
Pulmonary/Respiratory ...Orally, nasopharyngitis and oropharyngeal pain have been reported with use of a specific grape leaf extract AS195 KG) (53206). Sore throat, cough, allergic rhinitis, and nasopharyngitis have been reported with use of grape seed extract, but these effects occur at rates similar to placebo (9182,91541). One case report describes a 16-year-old female who developed increased levels of immunoglobulin E (IgE) following skin-prick exposure to grape vine pollen, as well as positive test responses following bronchial and conjunctival provocation (53301). Reduced forced vital capacity has been described in California grape workers (53080,53081). Occupational eosinophilic lung was diagnosed in a grape grower with a history of asthma. Respiratory exposure to sulfites in grape was implicated as the cause of the adverse reaction (53285).
Other
...Orally, grape products can cause adverse effects due to contamination with pesticides or mycotoxins.
Some evidence has shown that pesticides used in vineyards may remain on grape surfaces post-harvesting. For example, the fungicide folpet sprayed on grapevines has been shown to remain on the grape surface. Although there was minimal penetration of the epicuticular wax, it showed high resistance to washing (52935). Carbaryl has been identified in over 58% of juice samples collected in Canada. This pesticide reportedly occurred more frequently in grape than in other juices. However, estimates of short-term intake were below proposed acute reference doses (53003).
Ochratoxin A is a mycotoxin that is suspected to be nephrotoxic, teratogenic, hepatotoxic and carcinogenic and has been identified in grape juice, frozen grape pulps, and red and white wine sold in Rio de Janeiro, Brazil. However, the highest levels identified in grape products were lower than the established virtually safe dose of 5 ng/kg of body weight daily (53010,53004). Ochratoxin A has also been identified in red, but not white, grape juice marketed in Switzerland, Canada, and the U.S. (53292,53020).
General
...Orally, hawthorn seems to be well tolerated when used appropriately.
Topically, no adverse effects have been reported, although a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Multiorgan hypersensitivity reactions resulting in acute renal failure have been reported rarely.
Cardiovascular
...Orally, tachycardia (with facial pains) of uncertain relationship to hawthorn was reported in a multicenter clinical trial (54640).
Palpitations (19244) were reported in three patients in a large surveillance trial of 3,664 patients with cardiac failure (54692) and in 11 patients with congestive heart failure (CHF) in a literature review of 5,577 patients (19247). Circulation failure has been reported in two patients with CHF in a literature review of 5,577 patients (19247). Incidences of hospitalization, hospitalization due to CHF, worsening of CHF, angina, and atrial fibrillation have also been reported with the use of hawthorn extract WS 1442 (Crataegutt forte), although it is unclear if these events are related to hawthorn supplementation or existing CHF (19222). In clinical trials, chest pain (8281), short-term increases in blood pressure (19240), and other non-specific heart problems (17203) have also been reported following the use of various hawthorn preparations (e.g. WS 1442, Korodin).
Orally, severe bradycardia, bradypnea, and Mobitz type 1 second degree heart block have been reported in a 16-year-old female who consumed Hawthorn root extract. Blood tests indicated plasma digoxin levels in the therapeutic range, despite no history of digoxin use. Medical treatment for digoxin cardiotoxicity did not improve symptoms. Symptoms gradually normalized over 3 days after discontinuation of the product (113112). Similarly, a 40-year-old female presented with bradycardia and elevated plasma digoxin levels after taking hawthorn root extract 196 mg daily for 2 days with no history of digoxin use. Symptoms resolved within 24 hours (113113).
Dermatologic ...Orally, erythematous rash has been reported in patients with CHF in a literature review of 5,577 patients (19247). Non-specific rashes and itching (19222,19243) as well as toxiderma from the fruits of hawthorn (54670) have also been reported.
Gastrointestinal ...Orally, rare abdominal discomfort of uncertain relationship to hawthorn has been reported in a large clinical trial, surveillance study, case reports, and a literature review (19247,54640,54692,113112). Digestive intolerance (19241), diarrhea (19243,113112), flatulence (8281), gastroenteritis (8281), increased bowel movements (19243), obstipation (8281), mild and rare nausea (10144,19247,19244), vomiting (113112), nutritional and metabolic problems (17203), and other non-specific gastrointestinal effects (19222), have also been reported. Furthermore, gastrointestinal hemorrhage has been reported in two patients with CHF in a literature review of 5,577 patients (19247).
Musculoskeletal ...In clinical trials, arthritis (8281), back pain (8281), weakness (19243), and other non-specific musculoskeletal effects (19222) have been reported following the use of various hawthorn preparations g. WS 1442, CKBM-A01). Additionally, in a case report, myalgia has been reported following use of hawthorn root extract (113113).
Neurologic/CNS ...Orally, headache and dizziness/vertigo were reported in 2 patients in a large surveillance trial of 3,664 patients with cardiac failure (54692), in 15 patients with CHF as reported in a literature review of 5,577 patients (19247), in a varying number of clinical trial participants (8281,19222,19244), and in case reports (113112,113113). Incidences of fainting (19222), fever (17203), and infrequent, mild and transient sleepiness have also been reported (19221,54692).
Psychiatric ...Orally, agitation was reported in a large surveillance trial of 3,664 patients with cardiac failure (54692).
Pulmonary/Respiratory ...Orally, bronchitis has been reported following the use of hawthorn extract WS 1442 (8281), and bradypnea has been reported following the use of hawthorn root extract (113112).
Renal ...A case of multiorgan hypersensitivity reaction and acute renal failure following the consumption of C. orientalis has been reported (54654).
Other ...Flu-like syndrome (8281) and other non-specific infections have been reported following the use of the hawthorn extract WS 1442 (17203,19222). Hawthorn has also been reported to cause nosebleeds (8281,10144).
General
...Magnesium is generally well tolerated.
Some clinical research shows no differences in adverse effects between placebo and magnesium groups.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal irritation, nausea, and vomiting.
Intravenously: Bradycardia, dizziness, flushing sensation, hypotension, and localized pain and irritation. In pregnancy, may cause blurry vision, dizziness, lethargy, nausea, nystagmus, and perception of warmth.
Serious Adverse Effects (Rare):
All ROAs: With toxic doses, loss of reflexes and respiratory depression can occur. High doses in pregnancy can increase risk of neonatal mortality and neurological defects.
Cardiovascular
...Intravenously, magnesium can cause bradycardia, tachycardia, and hypotension (13356,60795,60838,60872,60960,60973,60982,61001,61031,114681).
Inhaled magnesium administered by nebulizer may also cause hypotension (113466). Magnesium sulfate may cause rapid heartbeat when administered antenatally (60915,114681).
In one case report, a 99-year-old male who took oral magnesium oxide 3000 mg daily for chronic constipation was hospitalized with hypermagnesemia, hypotension, bradycardia, heart failure, cardiomegaly, second-degree sinoatrial block, and complete bundle branch block. The patient recovered after discontinuing the magnesium oxide (108966).
Dermatologic ...Intravenously, magnesium may cause flushing, sweating, and problems at the injection site (including burning pain) (60960,60982,111696,114681). In a case study, two patients who received intravenous magnesium sulfate for suppression of preterm labor developed a rapid and sudden onset of an urticarial eruption (a skin eruption of itching welts). The eruption cleared when magnesium sulfate was discontinued (61045). Orally, magnesium oxide may cause allergic skin rash, but this is rare. In one case report, a patient developed a rash after taking 600 mg magnesium oxide (Maglax) (98291).
Gastrointestinal
...Orally, magnesium can cause gastrointestinal irritation, nausea, vomiting, and diarrhea (1194,4891,10661,10663,18111,60951,61016,98290).
In rare cases, taking magnesium orally might cause a bezoar, an indigestible mass of material which gets lodged in the gastrointestinal tract. In a case report, a 75-year-old female with advanced rectal cancer taking magnesium 1500 mg daily presented with nausea and anorexia from magnesium oxide bezoars in her stomach (99314). Magnesium can cause nausea, vomiting, or dry mouth when administered intravenously or by nebulization (60818,60960,60982,104400,113466,114681). Antenatal magnesium sulfate may also cause nausea and vomiting (60915,114681). Two case reports suggest that giving magnesium 50 grams orally for bowel preparation for colonoscopy in patients with colorectal cancer may lead to intestinal perforation and possibly death (90006).
Delayed meconium passage and obstruction have been reported rarely in neonates after intravenous magnesium sulfate was given to the mother during pregnancy (60818). In a retrospective study of 200 neonates born prematurely before 32 weeks of gestation, administration of prenatal IV magnesium sulfate, as a 4-gram loading dose and then 1-2 grams hourly, was not associated with the rate of meconium bowel obstruction when compared with neonates whose mothers had not received magnesium sulfate (108728).
Genitourinary ...Intravenously, magnesium sulfate may cause renal toxicity or acute urinary retention, although these events are rare (60818,61012). A case of slowed cervical dilation at delivery has been reported for a patient administered intravenous magnesium sulfate for eclampsia (12592). Intravenous magnesium might also cause solute diuresis. In a case report, a pregnant patient experienced polyuria and diuresis after having received intravenous magnesium sulfate in Ringer's lactate solution for preterm uterine contractions (98284).
Hematologic ...Intravenously, magnesium may cause increased blood loss at delivery when administered for eclampsia or pre-eclampsia (12592). However, research on the effect of intravenous magnesium on postpartum hemorrhage is mixed. Some research shows that it does not affect risk of postpartum hemorrhage (60982), while other research shows that intrapartum magnesium administration is associated with increased odds of postpartum hemorrhage, increased odds of uterine atony (a condition that increases the risk for postpartum hemorrhage) and increased need for red blood cell transfusions (97489).
Musculoskeletal
...Intravenously, magnesium may cause decreased skeletal muscle tone, muscle weakness, or hypocalcemic tetany (60818,60960,60973).
Although magnesium is important for normal bone structure and maintenance (272), there is concern that very high doses of magnesium may be detrimental. In a case series of 9 patients receiving long-term tocolysis for 11-97 days, resulting in cumulative magnesium sulfate doses of 168-3756 grams, a lower bone mass was noted in 4 cases receiving doses above 1000 grams. There was one case of pregnancy- and lactation-associated osteoporosis and one fracture (108731). The validity and clinical significance of this data is unclear.
Neurologic/CNS
...Intravenously, magnesium may cause slurred speech, dizziness, drowsiness, confusion, or headaches (60818,60960,114681).
With toxic doses, loss of reflexes, neurological defects, drowsiness, confusion, and coma can occur (8095,12589,12590).
A case report describes cerebral cortical and subcortical edema consistent with posterior reversible encephalopathy syndrome (PRES), eclampsia, somnolence, seizures, absent deep tendon reflexes, hard to control hypertension, acute renal failure and hypermagnesemia (serum level 11.5 mg/dL), after treatment with intravenous magnesium sulfate for preeclampsia in a 24-year-old primigravida at 39 weeks gestation with a previously uncomplicated pregnancy. The symptoms resolved after 4 days of symptomatic treatment in an intensive care unit, and emergency cesarian delivery of a healthy infant (112785).
Ocular/Otic ...Intravenously, magnesium may cause blurred vision (114681). Additionally, cases of visual impairment or nystagmus have been reported following magnesium supplementation, but these events are rare (18111,60818).
Psychiatric ...A case of delirium due to hypermagnesemia has been reported for a patient receiving intravenous magnesium sulfate for pre-eclampsia (60780).
Pulmonary/Respiratory ...Intravenously, magnesium may cause respiratory depression and tachypnea when used in toxic doses (12589,61028,61180).
Other ...Hypothermia from magnesium used as a tocolytic has been reported (60818).
