Copper Liver Chelate by SP Standard Process

POSSIBLY EFFECTIVE

• Athletic performance. Oral beet may improve athletic performance associated with aerobic activities. However, it is not clear who is most likely to benefit, for which type of competition it is most useful, or what dose or duration of use is most appropriate. Details: Several small clinical trials, most of which enrolled elite athletes, recreational athletes, and sedentary males, as well as meta-analyses of some of these and other studies, show that beet improves various measures of athletic performance, including ability, muscular endurance, power output, sprinting, and strength (93844,94464,94468,94469,100143,100150,100152,105761,113422). Clinical research also shows that drinking beetroot juice improves the use of oxygen during exercise testing in recreationally-trained athletes, especially with severe exercise testing (94460,94463,94467,100147,105762). Also, in obese adolescents, taking beetroot juice daily for 6 days increases the time to exhaustion from severe exercise, but does not improve moderate exercise (100145). Not all research shows that beet supplementation benefits athletic performance. Another meta-analysis of several small clinical studies, including some of the studies above, shows that taking beetroot does not improve performance in high-intensity or sprint interval training (111159). Additionally, the majority of research in elite athletes does not support the use of beetroot juice to decrease the time needed to complete a task, aid in some sort of graded exercise test, or improve the use of oxygen during exercise testing (94455,94458,94460,94461,94464,94465,94466,94469,94473,100142,100153,105763). The supposed lack of effect of beetroot juice in elite athletes might be related to the natural production of nitrates and nitrites in the body or the increased ability to use oxygen that comes from extensive training (94458,94463). Alternatively, any changes might be very small (<1%) and not identified with statistical comparisons, although even very small changes might be beneficial in competition (94464). The most commonly used doses in all studies, regardless of effect, have included an acute dose of beetroot juice 70-500 mL up to 3 hours prior to exercise (93844,94463,94464,94466,94467,94473,97726,100142,100143,105761)(105762,111159,113422) or chronic dosing of up to 500 mL daily for 3-6 days (94459,94464,94469,100145,100147,100153,111159,113422). Less commonly, beetroot juice 70-140 mL daily, betalain-rich concentrate 100 mg daily, or a beetroot-based nutritional gel 100 grams daily, have been taken for longer dosing schedules of 7-15 days (97720,100144,100148,100152,105763,113422). Benefits in elite athletes, most often related to time trials, are usually limited to studies using chronic dosing of 7-15 days, which is longer than the duration of 6 days used in the majority of studies (94473,97720,100144,100148). Brands of juice used in clinical trials have included Beet It Sport (James White Drinks Ltd.) (94455,94458,94465,100142,100143,100144,100148,105761,105763), Beet It Stamina Shot (James White Drinks Ltd.) (93844), Beet It (James White Drinks Ltd) (94457,94459,94460,94467,94469,97726,100145,100153,105762,111159), and Love Beets Beetroot Juice (Gs Fresh Ltd.) (94461,94462). Although plasma levels have not been analyzed in all studies, the majority of studies suggest that these doses are adequate to increase levels of nitrates or nitrites, which is thought to be essential for increasing athletic potential (93844,94455,94458,94459,94460,94465,94467,94469,94466,94473,97726). The evidence also suggests benefit in both normoxic and hypoxic environments (94465,100148,105763).
• Exercise-induced muscle soreness. Drinking beetroot juice 7-8 times over 48 hours after strenuous exercise may reduce exercise-induced muscle soreness, but evidence is conflicting. Details: Some clinical research shows drinking beetroot juice (Love Beets Beetroot Juice, Gs Fresh Ltd.) 125 mL or 250 mL seven times over 48 hours after strenuous box jumps improves muscle soreness when compared with placebo and sodium nitrite (96964,97722). Other small clinical studies show that drinking beetroot juice 50-250 mL as eight separate doses over 48 hours after strenuous exerciseimproves muscle soreness and reduces tissue edema when compared with placebo (94461,113424). However, drinking beetroot juice 250 mL as seven separate doses over 48 hours after running a marathon does not appear to reduce muscle soreness when compared with placebo (94462). A meta-analysis of 4 small studies, mostly in healthy or physically active males, shows that drinking beetroot juice improves the pressure pain threshold, which is a measure of muscle soreness, at 48- and 72-hours post-exercise when compared with a fruit-flavored drink. However, beetroot juice does not improve subjective muscle soreness scores (111160). The validity of the findings from this meta-analysis is limited by the heterogeneity of the beetroot juice regimens among the included studies. Further, these results should not be generalized to elite athletes.

POSSIBLY INEFFECTIVE

• Chronic obstructive pulmonary disease (COPD). Drinking beetroot juice for up to 14 days may not improve exercise capacity in patients with COPD. Details: A meta-analysis of eight small clinical trials in patients with COPD shows that taking nitrate-rich beetroot juice does not improve most measures of exercise capacity, including the 6-minute walk test, cycling ergometry endurance time, and maximum rate of oxygen consumption (VO2 max), when compared with placebo. Additionally, beetroot juice did not reduce blood pressure or heart rate. However, the analysis did show a significant improvement in scores on the Borg Rating of Perceived Exhaustion scale with beetroot juice over placebo. Nitrate-rich beetroot juice doses ranged from 70-140 mL daily for up to 14 days (104200).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cognitive function. It is unclear if drinking beetroot juice is beneficial for cognitive function. Details: A small clinical study in adults with overweight or obesity on a calorie-restricted diet shows that drinking 70 mL of concentrated beetroot juice daily for 14 days improves the time to complete part B of the trail making test, which is a test of cognitive function, but not part A, when compared with controls (111158). However, the duration and size of this study limits its validity. Further, it is unclear whether any improvement is clinically significant. The effect of acute beet administration on cognitive function has also been studied. A very small clinical study in healthy adults shows that taking beet extract (RedNite, Enovate Biolife) chewable tablets 3 grams 90 minutes prior to neuropsychological testing improves immediate and delayed memory capacity, frontal lobe function, and lexical flexibility but does not improve working memory, information processing speed, or subjective reports of memory performance when compared with placebo (113427).
• Coronary heart disease (CHD). It is unclear if oral beetroot extract is beneficial in patients with CHD. Details: A small clinical trial in patients with CHD shows that taking red beetroot extract 500 mg, containing around 25 mg betalains, twice daily for 2 weeks reduces total cholesterol and low-density lipoprotein (LDL) cholesterol by 15 mg/dL and reduces triglycerides by 8 mg/dL when compared to baseline. Slight improvements in blood pressure and blood glucose were also reported, but these changes were not clinically significant (103883). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear whether beetroot can reduce the risk of cardiovascular events in patients with CHD.
• Dyslipidemia. It is unclear if oral beetroot is beneficial in patients with dyslipidemia. Details: A meta-analysis of small clinical studies in healthy individuals or patients with dyslipidemia, cardiovascular disease, or overweight or obesity, shows that consuming beetroot juice or leaves does not improve levels of triglycerides or total, low-density lipoprotein, or high-density lipoprotein cholesterol when compared with controls (111163). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the enrolled patients and beetroot regimens.
• Exercise-induced muscle damage. It is unclear if oral beetroot juice improves recovery from muscle damage after exercise. Details: A meta-analysis of 4 small clinical studies in healthy or physically active individuals, most of which enrolled males only, shows that drinking beetroot juice improves measures of muscle recovery at 72 hours post-exercise when compared with a fruit-flavored drink. However, beetroot juice does not consistently improve recovery at earlier time points post-exercise, nor does it reduce levels of creatine kinase or markers of inflammation (i.e., interleukin-6, interleukin-8, c-reactive protein, or tumor necrosis factor-alpha) (111160). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the beetroot juice regimens among the included studies, which usually varied from 210-250 mg of nitrate in 7-11 servings over 3-7 days. Further, these results should not be generalized to elite athletes. Another very small clinical study in semi-professional female athletes shows that ingesting beetroot juice 50 mL 8 times over 48 hours after exercise-induced muscle damage enhances the recovery of some functional parameters such as muscle endurance but not others such as flexibility and vertical jump performance when compared with placebo (113424).
• Hypertension. Oral beet may slightly reduce blood pressure in healthy individuals, but it is unclear if it is beneficial in patients with hypertension. Details: Meta-analyses of small studies show the potential for a minor reduction in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in healthy adults taking beetroot juice (94470,97718,97728). The average reduction in SBP and DBP with beetroot juice consumption is about 4 mmHg and 1 mmHg, respectively, which is greater than the effect seen with consuming blackcurrant juice or nitrate-depleted beetroot juice. The most benefit is seen when beetroot juice is taken for at least 2 weeks or at doses of 500 mL daily (97728). The effect of acute beet supplementation on blood pressure is conflicting. A small clinical study in healthy adults shows that drinking beet juice (Beet It, James White Company) 140 mL two hours prior to cardiovascular measurements reduces resting SBP by about 4 mmHg but does not improve resting or post-exercise DBP, central blood pressure, or arterial stiffness nor does it improve post-exercise SBP when compared with placebo. Subgroup analysis suggests that the reductions in resting SBP were only observed in males, not females (113423). Another small clinical study shows that consuming beet 100 grams baked into bread modestly decreases DBP over a 6-hour period when compared with white bread (97725). It is possible that genetics might play a role in the magnitude of effect seen with beetroot consumption. Adults with a specific gene polymorphism, eNOS Glu298Asp, experienced a greater reduction in DBP after consuming beet-containing bread (97724). Despite positive findings in studies of healthy individuals, research on the use of beetroot juice in patients with hypertension is unclear. A small clinical study in adults with hypertension who were taking antihypertensive medications shows that drinking nitrate-rich beetroot juice (Beet it; James White Drinks Ltd.) 70 mL twice daily for one week does not lower blood pressure when compared with nitrate-depleted beetroot juice (94457). Also, in patients with mild to moderate hypertension, clinical research shows that taking a combination of beetroot powder (Sensient) 300 mg, olive leaf extract 1000 mg, and green coffee bean extract 200 mg daily for 6 weeks does not lower blood pressure when compared with placebo (97723). However, some evidence suggests that at least part of the blood pressure lowering effects of beet might be independent of nitrate (97728). Furthermore, some research suggests that identifying effects on blood pressure might be dependent on the method of measurement, including clinic resting measurements, 24-hour monitoring, or morning/evening home resting measurements (97729).
• Hypertriglyceridemia. It is unclear if oral beet is beneficial in patients with hypertriglyceridemia. Details: A small clinical study in overweight or obese individuals with dyslipidemia shows that taking freeze-dried beet leaf 2.8 grams daily for 4 weeks in addition to nutritional guidance does not lower triglyceride levels when compared with nutritional guidance alone (100146). Beet has also been evaluated in combination with other ingredients. A small clinical trial in patients at risk for heart disease shows that a specific combination of beet and hawthorn berry (Neo40-Daily, Neogenis Labs), taken twice daily for 30 days, can modestly reduce blood triglyceride levels when compared to baseline (18222). It is unclear if these findings are due to beet, hawthorn berry, or the combination.
• Liver disease. Although there has been interest in using oral beet for liver disease, there is insufficient reliable information about the clinical effects of beet for this purpose.
• Muscle strength. It is unclear if oral beetroot juice is beneficial for muscle strength. Details: A meta-analysis of 18 clinical studies in healthy males shows that taking beetroot juice or beetroot gel 2-3 hours before exercise improves muscular strength when compared with placebo. Subgroup analysis suggests that beetroot-based supplements improve muscular strength in a fatigued but not resting state (113422). A small clinical study in adults with overweight or obesity on a calorie-restricted diet shows that drinking 70 mL of concentrated beetroot juice daily for 14 days improves handgrip strength by approximately 18% compared with 4% in controls (111158). However, it is unclear whether any improvement is clinically significant.
• Obesity. It is unclear if oral beet leaf or beetroot juice is beneficial for weight loss. Details: A small clinical study in patients with overweight or obesity and dyslipidemia shows that taking freeze-dried beet leaf 2.8 grams daily for 4 weeks in addition to nutritional guidance does not reduce body weight or body mass index (BMI) when compared with nutritional guidance alone (100146). Similarly, a small clinical study in adults with overweight or obesity on a calorie-restricted diet shows that drinking 70 mL of concentrated beetroot juice daily for 14 days does not improve weight loss when compared with controls (111158). However, the size and duration of this study may have been inadequate to detect differences between groups.
• Pregnancy-induced hypertension. It is unclear if oral beetroot juice is beneficial in patients with pregnancy-induced hypertension. Details: A small clinical trial in pregnant patients with hypertension who are at approximately 22-35 weeks gestation shows that taking beetroot juice (James White Drinks Ltd) 70 mL daily for 8 days does not reduce blood pressure when compared with a nitrate-depleted beetroot juice (100151). However, the study was small and designed to investigate the feasibility of using beetroot juice in this population.
• Pulmonary hypertension. It is unclear if oral beetroot juice is beneficial in patients with pulmonary hypertension. Details: A small clinical study shows that taking beetroot juice (Beet-It Sport; James White Drinks Ltd) 70 mL twice daily for 7 days does not improve right ventricular systolic function when compared with nitrate-depleted beetroot juice in patients with pulmonary hypertension (100149). However, this study was small and not adequately powered to detect differences between groups.
• Raynaud syndrome. It is unclear if oral beetroot juice is beneficial in patients with Raynaud syndrome. Details: A small clinical study in patients with Raynaud syndrome undergoing cold sensitivity tests shows that drinking beetroot juice (Beet-It, James White Drinks Ltd) 70 mL daily for 13 days, followed by 140 mL prior to testing, does not reduce pain in the hands or feet, but might improve thermal comfort in the feet, when compared to baseline (103884). The validity of this finding is limited by the lack of a comparator group. More evidence is needed to rate beet for these uses.

(Read more about BEET)

POSSIBLY EFFECTIVE

• Vitamin A deficiency. Some preliminary clinical research shows that consuming one spoonful of carrot jam daily for 10 weeks improves growth velocity when compared with control in children with vitamin A deficiency (25819). Other preliminary research shows that consuming 100 grams of grated carrot daily for 60 days improves vitamin A status when compared with placebo in lactating women at risk for vitamin A deficiency (67861).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Breast cancer. A meta-analysis of observational research has found that consuming a diet highest in carrots is associated with a 21% decreased odds of developing breast cancer when compared with consuming a diet lowest in carrots (101715).
• Colorectal cancer. A large observational study in older Danish adults shows that self-reported high consumption of raw carrot (2-4 carrots weekly or greater than 32 grams daily) is associated with a 17% lower likelihood of colorectal cancer diagnosis, whereas lower carrot consumption is not associated with a decreased risk. The validity of these findings may be limited by selection bias, recall bias, and other confounding factors (106559).
• Fibromyalgia. Preliminary clinical research shows that consuming a mostly raw, pure vegetarian diet that includes two to four 240 mL servings of carrot juice daily for 7 months might improve fibromyalgia symptoms in some people (98057). The effect of carrot alone on fibromyalgia is unknown.
• Prostate cancer. Population research has found that higher intake of carrot is associated with an 18% decrease in the odds of developing prostate cancer. Increasing carrot consumption by 10 grams daily or 1 serving per week is associated with a 4% to 5% decrease in the odds of developing prostate cancer (96307). More evidence is needed to rate carrot for these uses.

(Read more about CARROT)

LIKELY EFFECTIVE

• Copper deficiency. Oral or intravenous copper is beneficial for treatment of copper deficiency. Details: Taking copper orally or intravenously is effective for treating copper deficiency and anemia due to copper deficiency. Copper deficiency is rare. It is seen most commonly in people receiving prolonged parenteral nutrition (7135). Oral cupric sulfate has been used in doses up to 0.1 mg/kg daily (7135). Copper 1-2 mg per day in parenteral nutrition solution has also been used (505).

POSSIBLY INEFFECTIVE

• Alzheimer disease. Oral copper does not seem to be beneficial for Alzheimer disease. Details: Preliminary clinical research shows that taking copper orotate dihydrate, providing 8 mg of elemental copper, daily for 12 months does not improve scores on evaluation scales for Alzheimer disease when compared with placebo (45949). There is also some concern that copper could have detrimental effects. Observational research has found that people with Alzheimer disease have higher levels of copper in their blood than people without the disease (95917); the clinical significance of this finding is unclear.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral copper 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 combination product containing copper (NicAzel, Elorac Inc.) 1-4 tablets daily for 8 weeks reduces inflammatory lesions in patients with inflammatory acne when compared with baseline. Other ingredients in this product include nicotinamide, azelaic acid, zinc, pyridoxine, and folic acid; specific quantities are not known (90800). The validity of this finding is limited by the lack of a comparator group.
• Brain tumor. It is unclear if oral copper is beneficial for use in glioblastoma. Details: A moderate-sized open-label clinical study in adults with first recurrence of glioblastoma receiving alkylating chemotherapy shows that taking elemental copper 2.5 mg with disulfiram 400 mg daily for 6 months does not improve survival but does result in significantly more adverse effects (e.g., elevated liver enzymes) when compared with control. The trial was stopped early due to safety concerns (112376).
• Cardiovascular disease (CVD). Although there is interest in using oral copper for CVD prevention, there is insufficient reliable information about the clinical effects of copper for this purpose.
• Chemotherapy-induced acral erythema. Oral copper has only been evaluated in combination with resveratrol; its effect when used alone is unclear. Details: A small clinical study in adults with advanced gastric cancers receiving docetaxel-based chemotherapy suggests that taking copper (Chelated Copper, JR Carlson Laboratories, LLC) with resveratrol three times daily for up to 6 months may reduce the incidence of grades 3 and 4 acral erythema (112377). However, the interpretation of these findings is limited by the lack of a control group.
• Chemotherapy-induced anemia. Oral copper has only been evaluated in combination with resveratrol; its effect when used alone is unclear. Details: A small clinical study in adults with advanced gastric cancers receiving docetaxel-based chemotherapy suggests that taking copper (Chelated Copper, JR Carlson Laboratories, LLC) with resveratrol three times daily for up to 6 months does not appear to reduce the incidence of grades 3 and 4 anemia (112377). However, the interpretation of these findings is limited by the lack of a control group.
• Chemotherapy-induced diarrhea. Oral copper has only been evaluated in combination with resveratrol; its effect when used alone is unclear. Details: A small clinical study in adults with advanced gastric cancers receiving docetaxel-based chemotherapy suggests that taking copper (Chelated Copper, JR Carlson Laboratories, LLC) with resveratrol three times daily for up to 6 months may reduce the incidence of grades 3 and 4 diarrhea (112377). However, the interpretation of these findings is limited by the lack of a control group.
• Chemotherapy-induced leukopenia. Oral copper has only been evaluated in combination with resveratrol; its effect when used alone is unclear. Details: A small clinical study in adults with advanced gastric cancers receiving docetaxel-based chemotherapy suggests that taking copper (Chelated Copper, JR Carlson Laboratories, LLC) with resveratrol three times daily for up to 6 months does not appear to reduce the incidence of grades 3 and 4 neutropenia or febrile neutropenia (112377). However, the interpretation of these findings is limited by the lack of a control group.
• Chemotherapy-induced nausea and vomiting (CINV). Oral copper has only been evaluated in combination with resveratrol; its effect when used alone is unclear. Details: A small clinical study in adults with advanced gastric cancers receiving docetaxel-based chemotherapy suggests that taking copper (Chelated Copper, JR Carlson Laboratories, LLC) with resveratrol three times daily for up to 6 months may reduce the incidence of grades 3 and 4 vomiting (112377). However, the interpretation of these findings is limited by the lack of a control group.
• Chronic venous insufficiency (CVI). It is unclear if compression stockings containing copper are beneficial for lipodermatosclerosis in patients with CVI. Details: Preliminary clinical research shows that using compression stockings impregnated with copper for 8 weeks does not improve overall symptoms of lipodermatosclerosis secondary to chronic venous disease when compared with using a compression stocking without copper. However, the affected surface area may be reduced by approximately 16% by 2 weeks when copper-impregnated compression stockings are used (101809).
• Dental plaque. It is unclear if rinsing the mouth with copper is beneficial for reducing dental plaque. Details: Preliminary clinical research shows that rinsing the mouth with a solution of copper 1.1 mmol/L for 4 days decreases plaque accumulation when compared with a placebo solution (46006).
• Diarrhea. Oral copper has only been evaluated in combination with zinc; its effect when used alone is unclear. Details: Preliminary clinical research in children 6 months to 5 years of age presenting to a hospital in India with acute watery or bloody diarrhea shows that taking a solution providing zinc 2 mg/kg and copper 0.2 mg/kg orally daily for 2 weeks does not reduce the duration of diarrhea, the weight of stool, or the need for rehydration when compared with placebo (87166). It also does not seem to reduce the recurrence of diarrhea or improve weight gain over the next 3 months (95540).
• Oral mucositis. Oral copper has only been evaluated in combination with resveratrol; its effect when used alone is unclear. Details: A small clinical study in adults with advanced gastric cancers receiving docetaxel-based chemotherapy suggests that taking copper (Chelated Copper, JR Carlson Laboratories, LLC) with resveratrol three times daily for up to 6 months may reduce the incidence of grades 3 and 4 oral mucositis (112377). However, the interpretation of these findings is limited by the lack of a control group.
• Osteoarthritis. Although there is interest in using topical copper for osteoarthritis, there is insufficient reliable information about the clinical effects of copper for this condition.
• Osteoporosis. Oral copper has only been evaluated in combination with other minerals; its effect when used alone is unclear. Details: Preliminary clinical research in postmenopausal adults shows that taking copper 2.5 mg in combination with zinc 15 mg, manganese 5 mg, and calcium 1000 mg daily for 2 years can slow bone loss when compared with taking either calcium or the trace minerals alone (1994).
• Postoperative infection. It is unclear if copper-impregnated wound dressings are beneficial for the prevention of postoperative infection. Details: Preliminary clinical research shows that using a wound dressing impregnated with copper oxide 3% by weight reduces the incidence of a surgical site infection in the 30-day period following a caesarean section by 39%, but does not reduce length of hospital stay or readmission rate, when compared with a non-copper wound dressing. Eight patients would need to be treated with the copper-impregnated dressing to prevent one infection (105363). This study is limited by the use of a telephone questionnaire to assess the suspicion of infection.
• Systemic lupus erythematosus (SLE). It is unclear if oral copper is beneficial for improving symptoms of SLE. Details: Copper status does not appear to be associated with the risk of SLE (101810). Additionally, one small clinical study shows that taking copper 3 mg daily, alone or in combination with fish oil, for 24 weeks does not affect symptoms of SLE when compared with placebo (12953).
• Tinea pedis. Although there is interest in using topical copper for tinea pedis, there is insufficient reliable information about the clinical effects of copper for this condition.
• Wound healing. It is unclear if topical copper sulfate can improve the healing of umbilical granuloma. Details: A small clinical study in children 1-3 months of age with treatment-naïve umbilical granuloma shows that a single application of copper sulfate to the affected site results in complete resolution in 70% of patients, compared with 90% of patients receiving topical sodium chloride twice daily for 5 days. Some patients who received a second application of copper sulfate experienced full healing; however, it is unclear if this was due to the treatment or natural resolution (109403). More evidence is needed to rate copper for these uses.

(Read more about COPPER)

POSSIBLY INEFFECTIVE

• Chronic fatigue syndrome (CFS). Daily injections of a combination of folic acid, bovine liver extract, and cyanocobalamin for 3 weeks appear to have no effect on CFS symptoms (7561).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Hepatitis C. Preliminary clinical research suggests that intravenous treatment with liver extract plus flavin adenine dinucleotide improves response to interferon-beta therapy in patients with hepatitis C (59952). Also, giving a specific combination of liver extract and flavin adenine dinucleotide (Adelavin) intravenously or intramuscularly appears to improve hepatitis C virus RNA levels in patients with hepatitis C who are being treated with interferon-alpha compared with those being treated with interferon-alpha alone. Researchers have attributed this effect to enhancement of 2'5'-oligoadenylate synthetase production (59964). More evidence is needed to rate liver extract for these uses.

(Read more about LIVER EXTRACT)

POSSIBLY INEFFECTIVE

• Cancer. A meta-analysis of 7 observational studies shows that potato consumption is not associated with a reduced risk of cancer-related death (103259). A meta-analysis of 56 studies shows that total daily potato intake is not associated with the overall incidence of cancer, and also is not associated with the incidence of cancers of the gastrointestinal tract, colon, rectum, pancreas, stomach, breast, kidney, lung, or bladder (111206).
• Colorectal cancer. A meta-analysis of 8 observational studies shows that potato consumption is not associated with a reduced risk of colorectal cancer (103261).
• Myocardial infarction (MI). A meta-analysis of 6 observational studies shows that potato consumption is not associated with a reduced risk of myocardial infarction (103261).
• Overall mortality. Meta-analyses of observational studies show that potato consumption is not associated with a reduced risk of all-cause mortality (103259,103261).
• Stroke. A meta-analysis of 6 observational studies shows that potato consumption is not associated with a reduced risk of stroke (103261).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cardiovascular disease (CVD). While one preliminary clinical study in healthy adults shows that consuming cooked purple potato 200 grams daily for 14 days can improve arterial stiffness, a marker of CVD, potato consumption does not seem to improve other CVD risk factors, including blood pressure, lipid levels, or markers of inflammation, when compared to baseline (103262). Additionally, epidemiological evidence shows that higher intake of boiled or fried potatoe does not increase or reduce the risk of CVD, hypertension, or elevated triglycerides (97751,111210).
• Dyspepsia. Preliminary clinical research in adults with dyspepsia shows that taking freshly squeezed potato juice 200-300 mL twice daily for one week improves gastrointestinal symptoms by 42% to 51% when compared with baseline (97757). The validity of this finding is limited by the lack of a comparator group.
• Hypertension. While a meta-analysis of 4 observational studies shows that potato consumption is not associated with a reduced risk of hypertension (103261), some preliminary clinical research in patients with hypertension shows that eating 6-8 small purple potatoes twice daily for 4 weeks reduces diastolic blood pressure by 4% when compared with baseline. Systolic blood pressure reductions are not statistically significant (97752). The validity of this finding is limited by the lack of a comparator group. Preliminary clinical research in people with pre-hypertension or mild hypertension shows that eating baked or boiled potatoes to provide potassium 85 mmol daily for 17 days lowers systolic blood pressure by 6 mmHg compared with a 2 mmHg decrease without potassium supplementation (107974). More evidence is needed to rate potato for these uses.

(Read more about POTATO)

LIKELY SAFE ...when used in amounts commonly found in foods.

POSSIBLY SAFE ...when used orally and appropriately for medicinal purposes, short term. Beetroot juice has been safely used in clinical trials in doses of up to 500 mL daily for up to 7 days and a beetroot-based nutritional gel has been used safely in doses of up to 100 grams daily for 8 days (94461,94462,94464,100149,100152,100153).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of beets used medicinally during pregnancy and breast-feeding.

(Read more about BEET)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Carrot essential oil, extracts, and food additives have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Carrot has been used safely in doses of approximately 100 grams three times daily for up to 4 weeks (96308). There is insufficient reliable information available about the safety of carrot when used topically.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (4912). Carrot essential oil, extracts, and food additives have Generally Recognized as Safe (GRAS) status in the US (4912).

CHILDREN: POSSIBLY UNSAFE
when carrot juices are used excessively in nursing bottles for small children. Excessive use of carrot juice may cause carotenemia and dental caries (25817).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food (4912). Carrot essential oil, extracts, and food additives have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of carrot when used in medicinal amounts during pregnancy and lactation.

(Read more about CARROT)

LIKELY SAFE ...when used orally and appropriately. Copper is safe in amounts that do not exceed the tolerable upper intake level (UL) of 10 mg daily (7135).

POSSIBLY SAFE ...when copper oxide is used topically. A wound dressing impregnated with copper oxide in concentrations of 3% by weight has been used with apparent safety in one clinical trial (105363).

POSSIBLY UNSAFE ...when used orally in doses exceeding the UL of 10 mg daily. Higher intake can cause liver damage (7135,45865). Kidney failure and death can occur with ingestion of as little as 1 gram of copper sulfate (17).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Copper is safe in amounts that do not exceed the tolerable upper intake level (UL) of 1 mg daily for 1-3 years of age, 3 mg daily for 4-8 years of age, 5 mg daily for 9-13 years of age, and 8 mg daily for 14-18 years of age (7135).

CHILDREN: POSSIBLY UNSAFE
when used orally in doses exceeding the UL (7135). Higher intake can cause liver damage (7135).

PREGNANCY: LIKELY SAFE
when used orally and appropriately. Copper is safe in amounts that do not exceed the tolerable upper intake level (UL) of 8 mg daily for those 14-18 years of age or 10 mg daily for those 19 years and older (7135).

PREGNANCY: POSSIBLY UNSAFE
when used orally in doses exceeding the UL. Higher intake can cause liver damage (7135).

LACTATION: LIKELY SAFE
when used orally and appropriately. Copper is safe in amounts that do not exceed the tolerable upper intake level (UL) of 8 mg daily for those 14-18 years of age or 10 mg daily for those 19 years and older (7135).

LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL. Higher intake can cause liver damage (7135).

(Read more about COPPER)

There is insufficient reliable information available about the safety of liver extract. However, since some preparations are derived from animals, there is concern about contamination with diseased animal parts (1825). So far, there are no reports of disease transmission to humans due to use of contaminated liver extract.

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

(Read more about LIVER EXTRACT)

LIKELY SAFE ...when unblemished, ripe potatoes are used as food (6).

POSSIBLY SAFE ...when unblemished, ripe potatoes are used orally for medicinal purposes (6). ...potato juice 200-300 mL has been consumed daily with apparent safety for up to 4 weeks (97757). ...a single dose of potato extract standardized to 15 mg or 30 mg protease inhibitor 2 (Slendesta, Kemin Foods) has been used with apparent safety (97755).

LIKELY UNSAFE ...when damaged, green potatoes and sprouts are consumed. These contain toxic solanum alkaloids that are not destroyed by cooking and can cause serious adverse effects (6). There is insufficient reliable information available about the safety of potato when used topically.

PREGNANCY AND LACTATION: LIKELY SAFE
when unblemished, ripe potatoes are used orally in food amounts. There is insufficient reliable information available about the safety of medicinal use of potato in pregnancy and lactation.

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CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, beet might decrease the levels and clinical effects of CYP1A2 substrates.  Details In vitro research suggests that beet induces CYP1A2 enzymes (111404).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, beet might increase the levels of CYP3A4 substrates.  Details In vitro research suggests that betanin, the major pigment in beet, competitively inhibits CYP3A4 in a dose-dependent manner similarly to strong CYP3A4 inhibitor ketoconazole (113425).

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CONTRACEPTIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking copper with contraceptive drugs might increase the levels and toxic effects of copper.  Details A meta-analysis of clinical studies suggests that chronic use of oral contraceptives increases serum copper levels by a mean of 57 mcg/dL. In most people, this resulted in levels above the normal reference range for copper (92395).

PENICILLAMINE (Cuprimine, Depen) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking copper with penicillamine might decrease the absorption of penicillamine; separate dosing by at least 2 hours.  Details Copper chelates penicillamine, which decreases its absorption and may reduce its clinical effects (4412,4453,4531,4535,9630).

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General ...Orally, beet seems to be well tolerated when used for medicinal purposes, short term.
Most Common Adverse Effects:
Orally: Red stools and red urine.
Serious Adverse Effects (Rare):
Orally: Hypocalcemia and kidney damage when ingested in large amounts.

Endocrine ...Theoretically, ingestion of large quantities of beets could lead to hypocalcemia because of the oxaluric acid content (18).

Gastrointestinal ...Orally, beet juice may cause red stools (94470,97726,100142,100145,105762). This red coloring of the stools is not harmful. Additionally, beet supplementation has been reported to cause black stools. In one case, a 79-year-old male on apixaban and clopidogrel presented with black stools, nausea, and vomiting after taking beet pills 2-3 days prior. The likelihood of upper gastrointestinal bleed was determined to be low based on factors such as normal vital signs and lack of severe anemia. The patient was diagnosed with beet-induced pseudo-hematochezia which was successfully treated with fluids and discontinuation of the beet supplement (113426).
Other less common gastrointestinal side effects include loose stools, constipation, and nausea (100149).

Genitourinary ...Orally, beet is known to produce red or pink urine (beeturia) in some people (32569,34134,94464,94470,97725,97726,100142,100145,100152,105762,113422). However, this red coloring of the urine is not harmful and dissipates after about 12 hours (113422).

Neurologic/CNS ...Orally, vivid dreams and worsening headaches have each occurred in one person in a clinical trial, although it is not clear if this is due to beet (97723).

Renal ...Theoretically, ingestion of large quantities of beets could lead to kidney damage due to its oxaluric acid content (18).

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General ...Orally, carrot is well tolerated when consumed as a food. It also seems to be generally well-tolerated when consumed as a medicine. Some people are allergic to carrot; allergic symptoms include anaphylactic, cutaneous, respiratory, and gastrointestinal reactions such as hives, swelling of the larynx, asthma, or diarrhea (25820,93606,106560). In infants, excessive consumption of carrot products in nursing bottles has been reported to cause extensive caries in the primary teeth (25817).
Topically, carrot has been associated with a case of phytophotodermatitis (101716).

Dental ...Orally, feeding carrot juice to infants, with or without sugar- or acid-containing beverages, has been reported to damage teeth and cause dental caries (25817).

Dermatologic ...Orally, excessive consumption of carrots or carrot-containing products can cause yellowing of the skin, which results from increased beta-carotene levels in the blood (25817). Carrots may cause allergic reactions in some patients. Allergic responses to carrot-containing foods include skin reactions such as hives, erythema, swelling, and/or papules (25820,96306).

Gastrointestinal ...Orally, carrots may cause allergic reactions in some patients. Allergic responses to carrot-containing foods can include gastrointestinal symptoms, such as diarrhea (25820).

Immunologic ...Orally, carrots may cause allergic reactions in some patients (25820,96306,106560). Allergic responses to carrot-containing foods can include skin reactions such as hives, erythema, swelling, and/or papules (25820,96306). For one patient, treatment of skin lesions resolved after a month of oral antihistamines and topical steroids, and avoiding further contact with carrot (96306). Allergic responses to carrot-containing foods can also include gastrointestinal symptoms, such as diarrhea, and respiratory symptoms, such as swelling of the larynx or asthma (25820). In one case, a patient with a history of allergic rhinitis and asthma who had been successfully treated with subcutaneous immunotherapy and was tolerant of consumption of raw and cooked carrots developed rhinoconjunctivitis when handling carrots. Inhalation of dust particles and aerosols produced by food processing activities and containing allergens from the peel and pulp of carrots is thought to have sensitized the airway, producing a distinct form of respiratory food allergy in which there are typically no symptoms with ingestion (106560).
Topically, a female runner developed phytophotodermatitis, which was considered possibly associated with the inclusion of carrot in a sunscreen (Yes To Carrots Daily Facial Moisturizer with SPF 15; Yes to, Inc.) (101716).

Psychiatric ...Compulsive carrot eating is a rare condition in which the patient craves carrots. According to one case report, withdrawal symptoms include nervousness, cravings, insomnia, water brash, and irritability (25821).

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General ...Orally, copper is generally well tolerated when consumed in doses below the tolerable upper intake level (UL).

Dermatologic ...Contact dermatitis caused by copper has been reported rarely. A case report describes a 5-year-old male who developed recurrent fingertip dermatitis and a positive skin test to copper after playing with toy cars made with a copper-containing alloy (95538). Also, in a small clinical trial in children 1-3 months of age with umbilical granuloma, 3 of 33 children receiving a single topical application of copper sulfate developed superficial burns, whereas no superficial burns occurred in those receiving topical sodium chloride (109403).
In one case report, a 68-year-old male with type 2 diabetes and peripheral neuropathy developed second- and third-degree burns after wearing a copper-containing compression sock on the right leg for 3 hours while sitting in the sun. The patient received treatment with topical silver sulfadiazine and oral clindamycin. After 6 weeks, the patient was found to have multiple persistent wounds containing necrotic tissue which required debridement, daily dressing changes, and tubular compression. It is thought that the heat conductance of copper magnified the effects of sun exposure in this case (109402).

Endocrine ...There is evidence from observational studies that people with diabetes (type 1 or type 2) have higher copper levels in their blood than people without diabetes, although not all studies have shown this (95537). It is not known if elevated copper levels contribute to development or worsening of diabetes.

Hematologic ...A case report of copper overdose in a 28-year-old male resulted in hemolysis exacerbated by glucose-6-phosphate dehydrogenase deficiency. The patient was hospitalized, received D-penicillamine chelation, blood transfusion, and ultimately, 4 cycles of plasmapheresis which led to clinical recovery (112378).

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General ...No adverse reactions have been reported. However, a thorough evaluation of safety outcomes has not been conducted, There is some concern about the possibility of contamination as liver extract is derived from raw animal liver gathered from slaughterhouses, possibly from sick or diseased animals (6616). There is also concern that liver extracts produced from cows in countries where bovine spongiform encephalitis (BSE) has been reported might be contaminated with diseased tissue (1825).

Immunologic ...There is concern that liver extracts produced from cows in countries where bovine spongiform encephalitis (BSE) has been reported might be contaminated with diseased tissue. Countries where BSE has been reported include Great Britain, France, The Netherlands, Portugal, Luxembourg, Ireland, Switzerland, Oman, and Belgium (1825). However, there have been no reports of BSE transfer to humans from contaminated liver extract products. Until more is known, tell patients to avoid these products unless the country of origin can be determined. Patients should avoid products that are produced in countries where BSE has been found.

Other ...There is some concern about the possibility of contamination of liver extract. Liver extract is derived from raw animal liver gathered from slaughterhouses, possibly from sick or diseased animals (6616). Products made from contaminated or diseased organs might present a human health hazard.

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General ...Orally, consuming whole, unblemished, ripe potatoes has not been associated with adverse effects. Drinking potato juice has resulted in heartburn, abdominal distension, diarrhea, and increased mucus production (97757). Potatoes absorb oil readily, increasing their energy content. Fried potatoes, potato chips, and French fries are commonly associated with weight gain (97752).
The solanum glycosides found in damaged, green potatoes and sprouts can cause sweating, headache, flushing, nausea, vomiting, diarrhea, abdominal pain, thirst, bronchospasm, and restlessness. Deaths have been reported (17,97758). These glycoalkaloids cannot be destroyed by cooking (97758).
When inhaled, potato dust is associated with a high incidence of respiratory symptoms due to bacterial and fungal contaminants (6).

Gastrointestinal ...Orally, potato juice has resulted in heartburn, abdominal distension, diarrhea, and increased mucus production (97757).
Glycoalkaloids found in damaged, green potatoes and sprouts can cause nausea, vomiting, diarrhea, abdominal pain, and thirst (17,97758). The glycoalkaloids in potato cannot be destroyed by cooking (97758).

Immunologic ...Orally, one case of food-dependent exercise-induced allergic reaction has been reported after potato consumption. A 31-year-old female experienced several acute, exercise-induced allergic reactions shortly after eating. Symptoms included widespread urticaria, palpitation, fever, faintness, vomiting, abdominal pain, and swelling of the eyelids, palms, and soles. Blood tests were positive for IgE antibodies to potato and negative for other foods she had eaten, suggesting that potato was the precipitating allergen (103260).

Neurologic/CNS ...Orally, glycoalkaloids found in damaged, green potatoes and sprouts affect the nervous system. This can cause sweating, headache, flushing, bronchospasm, and restlessness (17,97758). Severe poisoning can result in paralysis, respiratory insufficiency, cardiac failure, coma, and death (97758). The glycoalkaloids in potato cannot be destroyed by cooking (97758).

Pulmonary/Respiratory ...When inhaled, potato dust is associated with a high incidence of respiratory symptoms due to bacterial and fungal contaminants (6).

Other ...Potatoes absorb oil readily, increasing the energy content. Fried potatoes, potato chips, and French fries are commonly associated with weight gain (97752).
The solanum glycosides (glycoalkaloids) found in damaged, green potatoes and sprouts can cause toxicity at doses of approximately 2 mg/kg, and lethal poisoning at doses of approximately 3 mg/kg (97758). Levels of glycoalkaloids can increase post-harvest due to improper storage at higher temperatures, lower humidity, or areas with light. Also, mechanical damage or exposure to gamma-radiation or fungi increases these levels. Glycoalkaloids are concentrated in the peel; although when levels are high they also increase in the flesh of the tuber. Peeling will remove about 30% of the glycoalkaloids (97758).

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