Chewable Coenzyme Q10 100 mg [Discontinued] by Kirkman

EFFECTIVE

• Dyspepsia. Oral calcium carbonate is approved by the US Food and Drug Administration (FDA) as an antacid. Details: Taking calcium carbonate orally as an antacid is effective for treating dyspepsia (1843). Calcium carbonate has FDA approval as an antacid.
• Hyperkalemia. Intravenous calcium gluconate is approved by the US Food and Drug Administration (FDA) for preventing hyperkalemia-induced cardiac abnormalities. Details: Administering calcium gluconate intravenously can reverse electrocardiographic changes and arrhythmias induced by hyperkalemia (12946). Intravenous calcium gluconate is FDA-approved for preventing hyperkalemia-induced cardiac abnormalities.
• Hypocalcemia. Oral calcium treats and prevents hypocalcemia. Intravenous calcium is used to treat severe hypocalcemia. Details: Taking calcium orally is effective for treating and preventing hypocalcemia. Intravenous calcium gluconate, acetate, gluceptate, or chloride is effective for severe hypocalcemia or hypocalcemic tetany (12928).
• Kidney failure. Oral calcium carbonate or calcium acetate is used as a phosphate binder during kidney failure. Details: Taking calcium carbonate or calcium acetate orally is effective as a phosphate binder. Calcium acetate (PhosLo) appears to control hyperphosphatemia better than sevelamer (Renagel) (12943,12944,38990). Calcium citrate is not recommended for this purpose because it increases aluminum absorption and does not bind phosphate as efficiently as calcium acetate or calcium carbonate (21631). Some clinical research also shows that taking calcium orally reduces blood pressure in patients with kidney failure (975).

LIKELY EFFECTIVE

• Corticosteroid-induced osteoporosis. Oral calcium in combination with vitamin D prevents bone density loss that occurs during long-term treatment with corticosteroids. Details: Taking calcium in combination with vitamin D as adjunctive therapy seems to be effective for reducing bone mineral density loss in people using corticosteroids long-term (982,1046,1830,1831,1832,4462,4463,4464,4465,4466)(4467,12945,38493). One specific product used in clinical research is Oscal (Marion Merrel Dow Inc.), which contains elemental calcium 500 mg per tablet plus vitamin D 125 IU per tablet (982). Another product used is Oscal 250 + D (SmithKline Beecham Healthcare), which contains elemental calcium 250 mg and vitamin D 125 IU per tablet (1046).
• Hyperparathyroidism. Oral calcium reduces parathyroid hormone levels in patients with secondary hyperparathyroidism due to kidney failure. Details: Taking calcium orally reduces parathyroid hormone levels in patients with kidney failure and secondary hyperparathyroidism (1827,1828,1829,39174,39425). In elderly women, the combination of calcium and vitamin D reverses secondary hyperparathyroidism and reduces hip fracture risk (8818). Also, population research suggests increased calcium intake from the diet and supplements reduces the risk of primary hyperparathyroidism in women. Supplemental intakes of at least 500 mg/day and dietary intakes of approximately 1100 mg/day are considered to be protective (91353).
• Osteoporosis. Adequate calcium intake, from the diet and/or supplements, is recommended for the prevention and treatment of osteoporosis. Details: The Bone Health and Osteoporosis Foundation (BHOF) recommends ensuring adequate calcium intake in line with the recommended dietary allowance (RDA) by age, along with adequate vitamin D intake, for the prevention and treatment of osteoporosis in adults over 50 years of age. Supplementation can be used to augment dietary intake when adequate dietary intake is not feasible (109425). In the US and Canada, foods containing at least 200 mg calcium with less phosphorous content than calcium can be labelled with a health claim regarding the relationship between adequate calcium intake and a reduced risk for osteoporosis (11940,102148). However, calcium supplementation is not recommended specifically for the primary prevention of osteoporosis. The US Preventive Task Force (USPSTF) states that the current evidence is insufficient to assess the balance of benefits and harms of vitamin D and calcium supplementation, alone or in combination, for the primary prevention of fractures in community dwelling adults without osteoporosis (95695). Also, calcium supplements do not seem to be effective for preventing loss of bone mineral density (BMD) during lactation (988), in patients who have had bone marrow transplantation (1817), or in patients who have had renal transplantation (4823,38736,38871). Maximal bone growth occurs in the teenage years, and then BMD in females remains relatively constant until age 30-40. After age 40, bone loss typically occurs at rates of 0.5% to 1% per year. In males, this occurs several decades later. Bone loss is more pronounced if dietary calcium intake is below the RDA, which is the case for many Americans (2571,2578). One meta-analysis of randomized controlled trials in healthy children 7-14 years old shows that fortifying food with calcium 250-1000 mg daily for up to 24 months modestly improves femoral neck BMD, but not hip or spine BMD. However, the included trials did not supplement vitamin D (107232). During the 5 years immediately after menopause, calcium supplementation has very little effect on bone loss (2569,2570,2575,2576). The rapid loss of estrogen causes a high bone resorption rate, which increases serum calcium levels and therefore decreases intestinal absorption of calcium (2570). After this period, the typical rate of bone loss is 2% per year (2572,2576). Taking calcium 1000-1600 mg daily as carbonate, citrate, lactate gluconate, or citrate malate salt decreases this rate by 0.25% to 1% annually (977,979,981,2569,2571,2572,2575,2576,2578,6850)(38978,38980,39064). The greatest reductions (1% or more) are seen in the first 1-2 years of supplementation when bone remodeling foci can be filled (2569,2576). After this period, the differences in rate of loss between supplemented and non-supplemented females are closer to 0.25% per year (2569,2577). A meta-analysis of clinical evidence suggests that there is no additional benefit after 4 years (38980). Small clinical studies have found that continuous calcium supplementation at an average daily dose of 1050 mg, started after menopause and continued for 1.5-4 years, may reduce fracture rates by 26% when compared with no calcium supplementation. The largest of these studies was conducted in nursing home residents who also received daily vitamin D; the benefits of calcium, specifically, are unclear (39386). Some research also suggests that calcium and vitamin D improves primary prevention of osteoporotic fractures in some older individuals with osteoporosis, particularly the elderly and those who are no longer community dwelling (12930,38875,38849,39026,109471). However, not all research is positive. One large clinical trial in elderly adults with a low-trauma fracture show that taking calcium 1000 mg daily with or without vitamin D 800 IU daily for 2-7 years does not reduce the risk of a second fracture when compared with placebo (13073). Another clinical study shows that taking calcium 1000 mg daily plus vitamin D 800 IU daily does not prevent a second fracture in elderly patients, or prevent a first fracture in elderly patients with other risk factors such as low body weight (less than 58 kg, 127.6 pounds), smoking, family history of hip fracture, or fair or poor self-reported health (12929). Also, some exploratory research suggests that supplements may need to be continued indefinitely; in adults over 68 years of age, any effects of 2 years of calcium supplements on BMD appear to be lost within 2 years after discontinuing supplements (6853). Calcium has additive effects when used with other agents such as vitamin D, estrogens, or calcitonin. Whereas calcium alone generally reduces or prevents loss of BMD, combination with other agents can produce small increases in BMD ranging from 0.3% to 3.3% depending on the combination and dosages used (978,980,1836,2570,2571,2572,2576). However, one meta-analysis in healthy adults shows that fortifying foods with calcium 250-1000 mg daily, in conjunction with vitamin D supplementation, for up to 24 months does not improve BMD when compared with control (107232). The full potential of osteoporosis treatments cannot be realized without adequate calcium intake (2569,2570,2571,2572). Advise patients taking agents such as estrogens, calcitonin, bisphosphonates, or raloxifene (Evista) to ensure that their daily calcium intake meets the RDA. Use supplements if necessary. The usefulness of calcium in preventing osteoporosis in males is not as well-studied. Some observational research has found that calcium 870 mg daily is not associated with changes in BMD and bone loss in males (97201). However, clinical evidence suggests that taking calcium 1000 mg daily for 2 years might improve trabecular or cortical bone mass by 2% to 4% (980,8827,8873). Dietary supplementation with calcium and vitamin D seems to moderately reduce bone loss measured in the femoral neck, spine, and total body, and seems to reduce the incidence of nonvertebral fractures in older patients with osteopenia or low BMD (980).
• Premenstrual syndrome (PMS). Adequate calcium intake seems to prevent symptoms of PMS. Details: There seems to be a link between low dietary calcium intake and symptoms of PMS (2004,6847,39007). Taking calcium 1000-1336 mg daily seems to significantly reduce depressed mood, water retention, and pain, especially if daily calcium intake is inadequate (1822,1823,1824,2004,95821). Calcium carbonate 1200 mg daily seems to decrease PMS symptom scores by about 18% when compared with placebo (1822). Increasing dietary calcium intake is also associated with a decreased risk of developing PMS. Consuming an average of 1283 mg of calcium per day from foods is associated with about a 30% lower risk of developing PMS compared with consuming an average of 529 mg daily (13094); however, taking calcium supplements does not appear to be associated with the risk of developing PMS.

POSSIBLY EFFECTIVE

• Colorectal cancer. Oral calcium seems to be beneficial for preventing colorectal cancer, especially in those with adequate vitamin D levels and normal body mass index (BMI). Details: Population studies have found that increased intake of dietary or supplemental calcium is associated with a reduced risk of colorectal cancer and colorectal adenomas (1047,8820,12120,38951,98898,98899). Clinical trials and meta-analyses of clinical research also show that taking calcium supplements 1.2-2 grams daily for up to 4 years can reduce the risk of colorectal adenoma recurrence by up to 29% (970,12118,12950,15267,34596,38718,39042,95817). However, not all research has been positive. Some meta-analyses of clinical research or observational studies suggest that taking calcium does not reduce the risk of familial adenomatous polyposis or colorectal cancer (34596,39042,39349). Other contradictory research suggests that postmenopausal females who take calcium 1000 mg daily plus vitamin D 400 IU daily do not have a reduced risk of developing colorectal cancer (14290); however, this finding may not be reliable due to the high baseline intake of calcium in study participants. The reason for these conflicting findings is not entirely clear. Vitamin D might be an important factor. People with lower than average vitamin D levels do not seem to get any benefit from calcium supplements (12118). Also, one meta-analysis of previous trials suggests that taking calcium 1200 mg daily reduces the risk of colorectal adenomas in people with a normal BMI, but not in those who are overweight or obese (99715). Despite this conflicting evidence, the US Food and Drug Administration (FDA) approved a qualified health claim in 2005 stating that calcium supplements may reduce the risk of colorectal cancer and colorectal adenomas. However, the FDA has determined that there is little scientific evidence to support this claim (102366).
• Fetal bone mineralization. If calcium intakes are low during pregnancy, oral calcium seems to be beneficial for increasing fetal bone density. Details: With low dietary calcium intake (less than 562 mg elemental calcium daily) during pregnancy, calcium supplementation increases fetal bone mineralization and density. However, calcium supplementation does not offer any additional benefit if calcium intakes are adequate (3263,3264).
• Hypertension. Oral calcium seems to reduce blood pressure by a small amount. However, it is unclear if this reduction is clinically significant. Details: Many clinical trials and observational studies show that intake of calcium supplements or dietary calcium modestly reduces blood pressure in patients with or without hypertension, usually around 1-2 mmHg. Calcium seems to be more effective for certain subpopulations of patients, such as salt-sensitive people and patients with low baseline dietary calcium intake (945,972,974,976,984,1818,1819,1820,1821,6852)(13138,14406,38803,39063,39094,39221). Also, a meta-analysis of clinical research shows that calcium intake during pregnancy reduces systolic blood pressure in offspring by 1-2 mmHg (38852). However, a large-scale clinical trial in postmenopausal females shows that taking vitamin D (cholecalciferol) 400 IU daily in combination with elemental calcium 1000 mg daily does not lower blood pressure or reduce the risk of developing hypertension (16714). Additionally, a meta-analysis of 8 clinical trials shows that taking calcium in combination with vitamin D for up to 7 years has no effect on blood pressure (98861). The validity of this finding is limited by the poor methodological quality of the included studies. Some observational research suggests that calcium can reduce the risk for hypertension. Population research in females aged 45 years and older suggests that higher intake of calcium from both diet and supplement sources is linked to a lower risk of developing hypertension when compared to lower calcium intake (14265). In 2005, the US Food and Drug Administration (FDA) approved a qualified health claim stating that calcium supplements may reduce the risk of hypertension. However, the FDA has concluded that this claim is based on supporting, rather than conclusive, evidence (102367).
• Osteomalacia. Oral calcium seems to reverse osteomalacia caused by very low calcium intakes. Details: Osteomalacia is commonly caused by vitamin D deficiency; however, very low calcium intake can also lead to osteomalacia in children and adults. Calcium supplementation can reverse osteomalacia caused by calcium deficiency. Along with appropriate vitamin D supplementation, individuals at risk of osteomalacia need sufficient calcium intake (94819).
• Pre-eclampsia. Oral calcium seems to reduce the risk of pre-eclampsia in high risk pregnancies, especially if calcium intakes are low. Details: Although there is some conflicting evidence (971,38756), most clinical research shows that taking calcium orally 1-2 grams daily reduces pregnancy-related hypertension and pre-eclampsia (973,1833,8828,39043,39319,39426,96480). Calcium appears to reduce the risk of pre-eclampsia by about 50% when compared with placebo. One meta-analysis of 19 controlled trials involving over 29,000 pregnancies found that for every 19 females treated with calcium, one episode of pre-eclampsia would be avoided (96480). Calcium appears to have the greatest effect in individuals at high-risk of pre-eclampsia or with low calcium levels, and when taken at greater than or equal to 20 weeks of gestation (15029,38497,96480,99714). In 2005, the US Food and Drug Administration (FDA) approved a qualified health claim regarding the use of calcium supplements to reduce the risk of pregnancy-induced hypertension and pre-eclampsia. However, due to the limited and conflicting research available at that time, the FDA stated that this outcome was highly unlikely. Since then, large, high-quality clinical research has supported this finding. In fact, in 2016 the World Health Organization (WHO) released a recommendation to prescribe oral calcium supplementation 1.5-2 grams daily during pregnancies at high risk of pre-eclampsia if dietary calcium intakes are low, in order to prevent pre-eclampsia (97347).
• Rickets. Oral calcium seems to reverse rickets caused by very low calcium intakes. Details: Rickets is commonly caused be vitamin D deficiency; however, very low calcium intake can also lead to rickets. Calcium supplementation can reverse rickets caused by calcium deficiency (94819). A small clinical study in children with nutritional rickets shows that taking calcium 500-2000 mg daily for 24 weeks improves radiographically measured rickets caused by calcium deficiency. Rickets seems to improve more rapidly with calcium 1000 mg compared to calcium 500 mg. However, increasing the calcium dose to 2000 mg daily is not more beneficial than calcium 1000 mg daily (98904).
• Tooth retention. Oral calcium with vitamin D seems to help with tooth retention in the elderly population. Details: A clinical trial in the elderly population shows that taking calcium citrate malate 500 mg daily along with vitamin D3 (cholecalciferol) 700 IU daily orally for 3 years reduces the risk of tooth loss by about 52% when compared with placebo (8816).

POSSIBLY INEFFECTIVE

• Breast cancer. Oral calcium does not seem to be beneficial for breast cancer prevention. Details: Although some population research disagrees (15631,39041,95811,107237), most research shows that increased calcium intake is not associated with a reduced risk of breast cancer (15631,16715,98895,107236,107237). Subgroup analyses of population research suggest that calcium intake may reduce the risk of breast cancer in postmenopausal, but not pre-menopausal, adults (15631,107237). Another subgroup analysis in a large meta-analysis of population research also suggests that dietary intake may reduce estrogen receptor(ER)-negative breast cancer, but not ER-positive breast cancer (107236). However, most other research has not evaluated the effects of calcium supplementation or intake on breast cancer subtypes. The best evidence to date, from a large scale clinical trial (Women's Health Initiative), shows that taking vitamin D (cholecalciferol) 400 IU daily plus calcium 1000 mg daily for 7 years after menopause does not reduce the risk of developing invasive breast cancer at the end of the study and 5 years after the end of the intervention (16715,98895).
• Fractures. Although oral calcium prevents fractures in osteoporosis, most evidence shows that calcium does NOT prevent factures in people who do not have osteoporosis. See Osteoporosis discussion for more information on the use of calcium for this purpose. Details: The most recent and robust meta-analysis of clinical research shows that calcium supplementation with or without vitamin D is NOT associated with reduced fractures in older adults without osteoporosis (95822). A large-scale study in postmenopausal females aged 50-79 years suggests calcium 1000 mg plus vitamin D 400 IU daily for 7 years only modestly improves bone mineral density (BMD) and does not significantly reduce fracture risk. This lack of effect may have been due to low adherence to the treatment regimen. In those who were 80% adherent, the combination of calcium plus vitamin D reduced the risk of hip fracture by about 29% (14282). Also, some clinical research shows that taking calcium carbonate 1000 mg and vitamin D 400 IU for 5 years does not attenuate loss of height after menopause when compared with placebo (95810). Additional meta-analyses of clinical and observational evidence suggest that calcium supplementation is not associated with a reduced risk of vertebral or nonvertebral fractures, such as hip fractures (38589,38888,98895). Some other research has suggested that calcium in combination with vitamin D reduces fracture risk in older patients without osteoporosis (980,1836,8818,12930,12933,12952,38849,102145,107235); however, this research is confounded by a number of variables, including the presence of hormonal therapy and differing levels of fracture risk at baseline (1836,8818,95822). Conflicting findings on this topic might also be due to genetic differences in patient populations. A population analysis of the Women's Health Initiative study found that, in older females with the lowest genetic susceptibility to low bone mineral density (BMD), taking calcium with vitamin D is associated with a reduction in fracture risk. However, in females with a higher genetic susceptibility to low BMD, there is no association between supplementation and fracture risk. This might be because individuals with a lower susceptibility to low BMD are also more responsive to calcium and vitamin D supplementation (97357). As of April 2018, the U.S. Preventative Services Task Force (USPSTF) concludes that there is insufficient evidence to determine whether supplementing with vitamin D >400 IU daily along with calcium >1000 mg daily is safe and effective for preventing fractures in community dwelling adults without vitamin D deficiency, osteoporosis, or a history of fracture. USPSTF recommends against supplementing with calcium 1000 mg daily or less along with vitamin D 400 IU daily or less for preventing primary fractures in community-dwelling postmenopausal females (95695).
• Obesity. Oral calcium does not seem to improve weight loss. Details: Observational research has found that adults and children with low calcium intake are more likely to gain weight, have a higher body mass index (BMI), and be overweight or obese when compared to people with high calcium intake (12124,12125,12126,12127,14265). Additional observational research has found that increasing calcium intake is associated with weight loss in females; the results in males have been conflicting (12127,15602,15603). Despite these findings from observational research and a few small clinical studies (12128,15397,14438,98905), most clinical research has found that increased calcium intake does not increase weight loss (12052,13138,15396,15399,38985,39004,97356). The most recent meta-analysis of 20 clinical studies shows that daily dietary and supplemental calcium intake that meets the dietary reference intake (DRI) of 1000 mg or more daily does not increase weight loss in overweight individuals or patients with obesity when compared with intake below the DRI (95813). An older meta-analysis of 13 clinical trials also shows that increased dietary and supplemental calcium intake does not increase weight loss (15605).
• Overall mortality. Oral calcium does not seem to reduce overall mortality. Details: While some population research has found that calcium taken in combination with vitamin D in older females is associated with a lower risk of death (97353), most evidence shows that calcium, with or without vitamin D, has no effect on all-cause mortality (93533,97308).

INEFFECTIVE

• Cardiovascular disease (CVD). Oral calcium does not reduce the risk of developing CVD and may actually increase risk in some patients. Details: Clinical research shows that calcium does not decrease CVD risk. Several separate meta-analyses of clinical and population research involving over 50,000 patients show that taking calcium 600-1200 mg daily for up to 7 years does not reduce the risk of CVD-related outcomes, including stroke and myocardial infarction, cardiovascular death, or overall mortality (39018,91350,92994,93533,97308,98902,107231,107233). No association was found between total dietary or supplemental calcium intake with or without vitamin D and the risk of CVD or mortality (91350,93533,97308). In fact, some population and clinical research has found that when calcium is used alone or with vitamin D, there is an INCREASED risk of CVD and coronary heart disease (38077,107233). However, other clinical research disagrees (93533). One meta-analysis of high-quality randomized controlled trials shows that taking calcium for 2-7 years increases the risk of CVD and coronary heart disease by 1.1-1.2 times when compared with control. However, the majority of the included research evaluated postmenopausal females and it is unclear if this finding is applicable to other populations (107233).
• Chemotherapy-induced peripheral neuropathy. Intravenous calcium does not prevent nerve pain in patients given oxaliplatin. Oral calcium has not been evaluated for this purpose. Details: While pooled analyses of cohort studies and randomized controlled trials suggest that calcium and magnesium infusion decreases the incidence of oxaliplatin-induced neurotoxicity, a meta-analysis of only randomized controlled trials shows that the infusion has no effect in preventing neurotoxicity (90028,90029,90031). Additionally, clinical trials show that administering calcium gluconate 1 gram with magnesium sulfate 1 gram intravenously immediately before, or before and after, the administration of a single oxaliplatin cycle (90005), or over the entire 6-cycle course of oxaliplatin, does not improve symptoms of neurotoxicity when compared with placebo (96474).
• Myocardial infarction (MI). Oral calcium does not prevent MI. When taken in the absence of vitamin D, oral calcium may increase the risk of MI. Details: Population research has found that increased dietary intake of calcium is associated with a decreased risk of MI (91350). However, a 2010 meta-analysis of clinical research shows that taking calcium at a dose of at least 500 mg daily is associated with an approximate 30% INCREASE in the risk of MI in patients over the age of 40. According to this analysis, one additional case of MI will occur for every 69 patients that take calcium for 5 years (17482). A more recent meta-analysis of high-quality randomized controlled trials shows that taking calcium for 2-7 years increases the risk of MI by 1.2 times when compared with control. However, the majority of the included research studied postmenopausal females and it is unclear if this finding is applicable to other populations (107233) In contrast, other meta-analyses of clinical research have shown that taking calcium for up to 7 years is NOT associated with an increased risk of MI, including a meta-analysis that only included postmenopausal females (93533,107231). Reasons for these discrepancies are not entirely clear. It may relate to whether calcium is taken as monotherapy or in combination with vitamin D. When taken with vitamin D, which is commonly recommended, calcium supplementation does not appear to be associated with an increased risk of MI in postmenopausal females (93533). Also, the association between calcium supplementation and MI risk may be influenced by the amount of calcium consumed as part of the diet. Supplementation with calcium may be associated with an increased risk of MI in people with dietary calcium intake above 805 mg daily, but not in those with dietary calcium intake below 805 mg daily (17482)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. It is unclear if oral calcium is beneficial for alcohol use disorder. Details: Preliminary clinical research shows that taking calcium carbonate 800 mg and vitamin D 200 IU orally daily for 14 days modestly reduces alcohol craving scores and withdrawal scores when compared with placebo in adults with alcohol dependence that are undergoing withdrawal. Taking calcium carbonate did not reduce the need for diazepam; however, the study may have been inadequately powered to detect a difference between groups (107234).
• Atherosclerosis. It is unclear if oral calcium is beneficial for atherosclerosis. Details: A population study has found that taking calcium 1.2 grams daily for 3 years has no effect on carotid intima thickness or carotid atherosclerosis incidence. A total calcium intake (dietary and supplemental) of at least 1794 mg daily in older females may be associated with a decreased risk of carotid atherosclerosis when compared with a total calcium intake below 1010 mg daily (97351).
• Autism spectrum disorder. It is unclear if oral calcium during pregnancy is beneficial for reducing the odds of autism spectrum disorder in the offspring. Details: A small observational study found that calcium supplementation during pregnancy is associated with a 52% reduced odds of an autism spectrum disorder in the offspring (98900).
• Cancer. Oral calcium alone does not seem to prevent cancer. It is unclear if oral calcium with vitamin D is beneficial for preventing cancer. Details: Taking calcium alone does not seem to significantly reduce the risk of cancer (12118,15629). The role of calcium in cancer prevention when taken along with vitamin D is controversial, as conflicting results exist. One clinical trial shows that healthy postmenopausal females who take supplemental calcium 1400-1500 mg daily plus vitamin D3 (cholecalciferol) 1100 IU daily have a 60% lower relative risk for developing cancer of any type. Approximately 25 postmenopausal females would need to take this combination for 4 years to prevent one occurrence of cancer (15629). However, a more recent clinical study shows that healthy postmenopausal females who take supplemental calcium 1500 mg daily plus vitamin D3 (cholecalciferol) 2000 IU daily do not have a reduced risk of cancer at 4 years (93943). Reasons for the disparate results are not entirely clear. The discrepancies do not appear to be related to baseline vitamin D levels or different study populations. It is possible that, given the 10-year time lapse between the two publications, the discrepancies result from differences in cancer detection capability. Also, since cancer risk was a secondary outcome measure in the earlier study and a primary outcome measure in the more recent study, it is possible that the discrepancies result from differences in statistical methodologies. The effect of vitamin D and calcium on cancer risk in males and younger patients is not known. There is also interest in using calcium for reducing the risk of hematological malignancies. An analysis of the Women's Health Initiative study shows that taking calcium 1000 mg daily in combination with vitamin D3 400 IU for up to 10 years is associated with a 20% reduction in the risk of hematologic malignancies when compared with placebo. However, no effect on hematologic malignancy related mortality was seen (97354).
• Depression. It is unclear if oral calcium is beneficial for depression prevention. Details: Population research has found no association between a higher dietary intake of calcium and the risk of depression when compared with a lower dietary intake of calcium (96480).
• Diabetes. It is unclear if oral calcium is beneficial for type 2 diabetes prevention. Details: Some population research has found that a higher intake of calcium from diet or supplements, alone or in combination with vitamin D, is associated with a lower risk of developing type 2 diabetes when compared with lower calcium intake (14265,16713,96473). However, population research is often limited by confounding variables. For example, one analysis found that any beneficial effect might be influenced by concomitant magnesium intake (96473). Furthermore, other population research has found that serum calcium levels higher than 9.6 mg/dL are associated with greater risk of developing diabetes in Chinese adults with osteoporosis. This study is limited because it was not determined whether increased serum calcium was due to increased calcium intake or another factor such as parathyroid function (95815).
• Dysmenorrhea. It is unclear if oral calcium is beneficial for reducing pain associated with dysmenorrhea. Details: Clinical research shows that taking calcium carbonate 1000 mg with vitamin D 5000 IU daily for three menstrual cycles does not reduce pain when compared with placebo in patients with primary dysmenorrhea (95821). However, calcium carbonate 1000 mg taken alone seems to reduce pain when compared with placebo.
• Endometrial cancer. It is unclear if oral calcium is beneficial for endometrial cancer prevention. Details: A meta-analysis of population research suggests that calcium supplements may reduce the risk of endometrial cancer, but dietary calcium does not seem to have any effect (38893).
• Fall prevention. It is unclear if oral calcium with vitamin D is beneficial for preventing falls. Details: Research suggests that calcium in combination with vitamin D, but not calcium alone, might prevent falls by decreasing body sway and normalizing systolic blood pressure (6362,11939,39038). Some experts think the combination of calcium and vitamin D may be important (11916). Preliminary clinical research in adults residing in a health care facility shows that taking vitamin D supplements while increasing dietary calcium and protein for 2 years reduces falls by 11% when compared with standard diets. Intervention diets were supplemented with milk, yogurt, and cheese to provide calcium 1142 mg and protein 69 grams daily (107235). There might also be different effects in females compared to males. In one study, females aged 65 years or older who took vitamin D 700 IU plus calcium citrate 500 mg daily over a 3-year period had a 46% lower risk of falling. However, this combination did not decrease falls in males (14291).
• Fluorosis. Oral calcium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Taking calcium orally, in combination with ascorbic acid (vitamin C) and vitamin D, seems to be effective for reducing excessive fluoride levels in children and improving symptoms of fluorosis in children aged 6-12 years (990).
• Heart failure. It is unclear if oral calcium in combination with vitamin D is beneficial for preventing heart failure. Details: Based on a secondary analysis of a large-scale clinical trial (Women's Health Initiative), taking calcium 1000 mg with vitamin D 400 IU daily does not reduce the risk of heart failure in the overall population or in individuals at high risk. However, in a subgroup of postmenopausal females without risk factors for heart failure, calcium and vitamin D supplementation might reduce the risk of developing heart failure by about 37% (97307).
• Hypercholesterolemia. It is unclear if oral calcium is beneficial for hypercholesterolemia. Details: Some evidence shows that taking calcium carbonate 400 mg three times daily reduces low-density lipoprotein (LDL) cholesterol levels by 4% and increases high-density lipoprotein (HDL) cholesterol levels by 4% after 6 weeks of treatment when used in combination with a low-fat diet (American Heart Association Step 1) (2557). In contrast, a study in females with dyslipidemia shows that taking calcium 800 mg daily for 2 years might INCREASE total cholesterol levels by about 12 mg/dL when compared with placebo. This same study showed an association between calcium supplementation and an increase in total cholesterol levels and carotid intimal thickness in postmenopausal females, but not premenopausal females (97350). A recent meta-analysis of randomized controlled trials which included both healthy patients and patients with dyslipidemia shows that taking calcium 500-2000 mg daily and vitamin D 200-7142 IU daily modestly improves HDL cholesterol and triglyceride levels, but not LDL cholesterol levels, when compared with placebo. Subgroup analyses suggest that calcium and vitamin D supplementation is more effective in patients with dyslipidemia at baseline. It is unclear if this effect is due to calcium, vitamin D, or the combination (107227). However, other research shows that taking a specific supplement containing calcium 600 mg plus vitamin D 200 IU (Caltrate 600 D, Wyeth Consumer Healthcare Inc.) twice daily in combination with calorie restriction does not reduce total or LDL cholesterol levels when compared with placebo (15601).
• Lead toxicity. It is unclear if oral calcium is beneficial for reducing blood levels of lead. Details: Lead is mobilized along with calcium from bone during pregnancy and lactation, resulting in increased serum concentrations of lead. One clinical study suggests that calcium supplementation does not significantly decrease these elevated lead concentrations (1586). However, another clinical study suggests that taking calcium reduces blood lead levels by 11% when compared with placebo, with greatest effects observed in those with high baseline levels of lead (38957).
• Lyme disease. Although there is interest in using oral calcium for Lyme disease, there is insufficient reliable information about the clinical effects of calcium for this condition.
• Metabolic syndrome. It is unclear if oral calcium alone or with vitamin D is beneficial for metabolic syndrome prevention. Details: Population research has found that a higher intake of calcium from diet and supplements alone, or in combination with vitamin D, is associated with a lower risk of developing metabolic syndrome when compared with lower calcium intake (14265,16713).
• Nephrotic syndrome. It is unclear if oral calcium with vitamin D is beneficial for preventing nephrotic syndrome. Details: Clinical research shows that taking calcium 500-1000 mg daily for 3 months in combination with vitamin D3 60,000 IU daily or weekly for 4 weeks has no effect on bone mineral density or the risk of relapse in children with steroid-sensitive nephrotic syndrome (97355).
• Nonmelanoma skin cancer. It is unclear if oral calcium is beneficial for preventing keratinocyte carcinomas. Details: In middle aged and older adults recently diagnosed with a colorectal adenoma, clinical research shows that taking calcium 1200 mg daily as calcium carbonate for 3-5 years does not reduce the incidence of keratinocyte cancer when compared with placebo over a median of 8 years. A sub-group analysis shows that taking calcium alone or with vitamin D3 1000 IU daily reduced the risk of invasive cutaneous squamous cell carcinoma by a moderate amount, but had no effect on the risk of basal cell carcinoma (104622).
• Oral mucositis. When used in combination with fluoride treatments, a calcium phosphate mouth rinse seems to prevent and reduce mucositis-related pain in patients undergoing hematopoietic stem cell transplantation (HSCT). Details: A small clinical study in patients undergoing HSCT shows that using a particular mouth rinse (Caphosol, EUSA Pharma) containing calcium phosphate, in combination with fluoride treatments, reduces days of mucositis, the duration of pain, and the dose and days of morphine used when compared with placebo and fluoride treatment (38611).
• Ovarian cancer. It is unclear if oral calcium is beneficial for ovarian cancer prevention. Details: An older meta-analysis of 12 cohort studies found that dietary calcium intake is not associated with a reduced risk of ovarian cancer (38792). However, a more recent pooled analysis of 15 cohort and case-control studies has found that the highest intake of dietary or dairy calcium is associated with a 20% lower risk of ovarian cancer when compared to the lowest intake (97349).
• Postpartum depression. It is unclear if oral calcium is beneficial for reducing postpartum depression risk. Details: Preliminary clinical research shows that taking calcium 2 grams daily beginning at 11-21 weeks gestation reduces depression at 12 weeks postpartum when compared with placebo. However, no benefit is seen at 6 weeks postpartum (39447).
• Pregnancy-related leg cramps. It is unclear if oral calcium is beneficial for preventing leg cramps during pregnancy. Details: A small clinical study shows that taking calcium 1 gram twice daily (as a mixture of salts) for 2 weeks can reduce pregnancy-related leg cramps during the second half of pregnancy when compared with no treatment (2567).
• Prostate cancer. It is unclear if oral calcium is beneficial for prostate cancer prevention. Details: Some clinical research shows that taking calcium 1200 mg daily might decrease the risk of developing prostate cancer (14133). However, some epidemiological research suggests that consuming very high doses of calcium, over 2000 mg daily, might actually increase the risk of developing prostate cancer (14134). Some epidemiological research also suggests that doses greater than 1500 mg daily increase the risk of poorly differentiated, clinically advanced, and fatal prostate cancer (14132). Consumption of dairy products has also been weakly linked to a modest increase in risk of prostate cancer (98894). However, contradictory research suggests that there is no association between dietary intake of calcium and overall risk of prostate cancer (14131,14132,104630).
• Stroke. It is unclear if oral calcium is beneficial for stroke prevention. Details: Some population research has found that increasing dietary calcium intake is associated with a decreased risk of ischemic stroke (4822,38678). However, other population research has found that increasing dietary calcium intake is not associated with a decreased risk of stroke (91350). One meta-analysis of high-quality randomized controlled trials shows that taking calcium for 2-7 years does not affect the risk of stroke when compared with control. However, the majority of the included research evaluated postmenopausal females, and it is unclear if this finding is applicable to other populations (107233).
• Vertigo. Oral calcium with vitamin D might reduce positional vertigo; the effect of calcium when used alone is unclear. Details: A large clinical study in adults with recurrent benign paroxysmal positional vertigo shows that taking calcium 500 mg and vitamin D 400 IU twice daily for one year reduces annual recurrence of vertigo by 27% when compared with no treatment. The number needed to treat to prevent vertigo was 3.7 (103681). It is unclear if this benefit is due to vitamin D, calcium, or the combination. More evidence is needed to rate calcium for these uses.

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LIKELY EFFECTIVE

• Coenzyme Q10 deficiency. Taking coenzyme Q10 orally improves symptomatic deficiency. Details: Rare cases of acquired coenzyme Q10 deficiency with symptoms of weakness, fatigue, and seizures have been reported (8160,8161). In adults, deficiency can be treated with coenzyme Q10 orally, 150-2400 mg daily in up to three divided doses. In children, 30 mg/kg, or 60-250 mg daily in up to three divided doses has been used (8160,8161,89417). Data from several multinational disease registries has also evaluated the use of coenzyme Q10 in patients with primary coenzyme Q10 deficiency, a rare genetic disorder. This data indicates that patients who take coenzyme Q10 supplements have a mean reduction of 88% in proteinuria at 12 months when compared with patients who do not take coenzyme Q10. In patients under 18 years of age with primary deficiency and chronic kidney disease at baseline, taking coenzyme Q10 supplements is associated with a 5-year survival without kidney failure of 62%, compared with 19% for those not taking coenzyme Q10 (108956).
• Mitochondrial myopathies. Taking coenzyme Q10 orally seems to reduce symptoms in some patients with genetic and acquired mitochondrial dysfunction. Details: A specific coenzyme Q10 formulation (UbiQGel, Tishcon Corporation) has been evaluated for mitochondrial myopathies, including MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome, Kearns-Sayre syndrome, and MERRF (myoclonus epilepsy with ragged red fibers). Typical doses are 150-160 mg, or 2 mg/kg, daily, gradually increasing to 3000 mg daily in some cases. The onset of action is slow, with maximal effects around 6 months (8159,8162,8163,8912,11050,44240,97905).

POSSIBLY EFFECTIVE

• Congestive heart failure (CHF). Oral coenzyme Q10 may provide benefit to patients with CHF by improving some, but not all, measures of disease severity when given in combination with conventional therapy. Details: Population research has found that CHF is associated with low coenzyme Q10 levels that correlate with severity of disease, and may be a predictor of mortality risk (44059,44220). A 2017 meta-analysis of clinical research shows that taking coenzyme Q10 30-300 mg, or 2 mg/kg, orally daily in two or three divided doses for up to 2 years, in addition to conventional therapy, improves exercise capacity, reduces hospitalizations, and reduces mortality by about 30% when compared with placebo. Other clinical research shows that adding oral coenzyme Q10 seems to improve quality of life and decrease symptoms of CHF such as dyspnea, peripheral edema, enlarged liver, and insomnia in patients with mild to severe (New York Heart Association (NYHA) class II-IV) CHF (6037,6038,6407,6408,6409,8909,12170,43967,43971,44042)(44277,44288,44289,44304,44334,44352,95610,96542). Additional clinical research shows that taking coenzyme Q10 30 mg daily for 1 year in addition to standard care reduces the incidence of atrial fibrillation by about 73% when compared with standard care alone in patients with NYHA class II-IV CHF (95609). However, not all evidence is positive. Some research suggests that coenzyme Q10 does not improve objective measures of CHF, including left ventricular ejection fraction (LVEF), cardiac output, or NYHA classification (5090,5248,6037,6038,43904,43932,96542,43932,97902). It is possible that the benefit of coenzyme Q10 depends on the dose and duration, the severity of CHF, and the specific conventional therapies taken concurrently (43973). A meta-analysis of 11 small, low-quality studies concludes that coenzyme Q10 probably reduces risk of all-cause and cardiovascular mortality, and of hospital admission for CHF, but data on improvement in LVEF or exercise capacity and the risk for myocardial infarction and stroke are inconclusive. However, the included studies used a range of coenzyme Q10 doses, varying concurrent therapy, short follow-up periods, and variable measures of treatment effect (108954). In patients with CHF with preserved ejection fraction (HFpEF) and a LVEF of 50% or greater, taking coenzyme Q10 600 mg daily for 12 weeks reduces B-type natriuretic peptide levels and improves Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, level of vigor, and LVEF when compared with placebo (108959).
• Diabetic neuropathy. When taken alone or as add-on treatment with pregabalin, most research suggests that oral coenzyme Q10 reduces symptoms in patients with diabetes and neuropathy. Details: Clinical research shows that taking coenzyme Q10 400 mg orally daily for 12 weeks significantly improves nerve conduction and symptoms of neuropathic pain when compared with placebo in diabetic patients with polyneuropathy (44217). The beneficial effects of coenzyme Q10 have also been investigated as an add-on treatment in patients taking pregabalin 150 mg daily. Clinical research shows that taking coenzyme Q10 100 mg three times daily for 8 weeks reduces pain severity and sleep interference due to pain when compared with placebo. The proportion of patients taking coenzyme Q10 with a decline in pain of at least 50% was 47%, compared with 27% of those taking placebo. Despite these findings, there was no difference in patient global improvement (109391). However, some research disagrees. One clinical trial shows that taking coenzyme Q10 (Health Burst) 200 mg daily for 12 weeks does not affect neuropathic symptoms, including pain, sensations, and strength, when compared with placebo (109386).
• Fibromyalgia. Oral coenzyme Q10 seems to improve both physical and psychological symptoms of this condition. Details: Clinical research in women with fibromyalgia shows that taking coenzyme Q10 300-400 mg orally daily for 40 days to 3 months improves pain by 24% to 56%, fatigue by 22% to 47%, sleep disturbances by 33%, morning tiredness by 56%, and tender points by 44% when compared with placebo. Patients also experience an improvement in psychological symptoms, including depression and anxiety (89416,97912,97913).
• Ischemia-reperfusion injury. Oral or intravenous coenzyme Q10 may help reduce hypoxic damage during cardiac bypass or vascular surgery. Details: Clinical research shows that taking coenzyme Q10, 150-300 mg orally daily in up to 3 divided doses for 1-2 weeks before cardiac bypass or vascular surgery, or 5 mg/kg IV two hours prior to surgery, reduces hypoxic damage during the surgery (11902,11903,44031,44294). However, coenzyme Q10 has no effect on cardiac function or troponin levels (11904,44292).
• Migraine headache. The American Academy of Neurology considers oral coenzyme Q10 to be possibly effective for migraine prevention in adults. Its benefit in children is unclear. Details: Two small open-label, non-randomized clinical trials in adults show that taking coenzyme Q10 100-150 mg daily decreases the frequency of headaches by up to 50% when compared with baseline or control, although it can take up to 3 months to see benefit (8135,95608). Higher quality research suggests a smaller benefit. A meta-analysis of small randomized controlled trials in adults shows that taking coenzyme Q10 alone or with other supplements reduces migraine attacks by 1.5 times per month and reduces duration of migraines by about 12 minutes when compared with control (105070). In children and adolescents, some clinical research shows that taking coenzyme Q10 orally, as 100 mg daily or 1-3 mg/kg daily, for 12-16 weeks does not improve headache frequency, severity, or duration when compared with placebo. However, it may reduce migraine frequency in children with low coenzyme Q10 levels (15256,44197). However, another clinical study shows that taking coenzyme Q10 daily is less effective than amitriptyline after one month, but as effective after 3 months, for improving headache frequency, severity, or duration, as well as quality of life. In this study, the dose of coenzyme Q10 was based on weight; 30 mg daily for children weighing less than 30 kg and 60 mg daily for children weighing at least 30 kg (109388).
• Multiple sclerosis (MS). Oral coenzyme Q10 seems to reduce fatigue and depression associated with MS. Details: Clinical research shows that taking coenzyme Q10 500 mg orally daily for 3 months reduces fatigue and depression in patients with MS when compared with placebo (96539).
• Muscular dystrophy. Oral coenzyme Q10 seems to improve physical performance in patients with muscular dystrophy of various forms. Details: Two small clinical studies show that taking coenzyme Q10 orally 100 mg daily for 3 months seems to improve physical performance when compared with placebo in some patients with various muscular dystrophies (2127).
• Myocardial infarction (MI). Oral coenzyme Q10 seems to reduce cardiac events and improve survival in patients who have had an MI. It is unclear if coenzyme Q10 improves survival in patients after cardiac arrest. Details: One small clinical study in patients with acute MI shows that starting coenzyme Q10 60 mg twice daily within 72 hours of the MI appears to significantly reduce the risk of cardiac events, including non-fatal MI and cardiac death, by 52% when administered for 28 days and by 45% when administered for up to one year (10152,44330). Also, a small clinical study in patients with recent MI who received cardiopulmonary resuscitation, shows that administering a 250 mg loading dose of coenzyme Q10 solution followed by 150 mg three times daily through a nasogastric tube for 5 days improves the 3-month survival rate by 134% when compared with placebo (43935). However, another clinical study in a similar patient population conducted to replicate these results shows that administering coenzyme Q10 300 mg in 50 mL of Ensure every 12 hours for 7 days does not improve in-hospital mortality or neurological outcomes when compared with placebo (105068).
• Peyronie disease. Coenzyme Q10 taken orally may reduce Peyronie disease severity. Details: Clinical research shows that, in patients with early chronic Peyronie disease, taking coenzyme Q10 (Kaneka Nutrients, Osaka) 300 mg orally daily for 24 weeks reduces new plaque formation and plaque size and improves erectile function when compared with placebo. Additionally, disease progression is slowed in about 76% of patients (44180).

POSSIBLY INEFFECTIVE

• Alzheimer disease. Coenzyme Q10 appears to be ineffective for improving cognition. Details: One clinical study shows that taking coenzyme Q10 1200 mg orally daily for 16 weeks does not improve cognition scores when compared with placebo in patients with Alzheimer disease (19206).
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Oral coenzyme Q10 does not attenuate functional decline in ALS patients. Details: Clinical research shows that taking coenzyme Q10 2700 mg orally daily for 9 months does not significantly attenuate a decline in ALS functioning scores when compared with placebo (44131). Higher doses, up to 3000 mg daily, have been tolerated by patients with ALS for 5 months, although the effect on ALS functioning at this dose is not known (43955).
• Chemotherapy-related fatigue. Oral coenzyme Q10 does not seem to help with fatigue due to chemotherapy. Details: Clinical research shows that taking coenzyme Q10 100 mg orally three times daily for 24 weeks does not reduce chemotherapy-related fatigue or improve quality of life when compared with placebo in breast cancer patients undergoing chemotherapy with or without radiation (89420).
• Diabetes. Most clinical research does not show any benefit with oral coenzyme Q10 in patients with type 1 or type 2 diabetes. However, some research suggests a possible benefit on insulin resistance. Details: Although a recent meta-analysis and some individual clinical research shows that coenzyme Q10 modestly reduces fasting glucose levels and glycated hemoglobin (HbA1c) in patients with type 1 or type 2 diabetes, most clinical research shows that coenzyme Q10 has no clinically meaningful effect on these parameters (456,492,2126,9890,96544,97911,97918,99636,11877,17704,44023,103778,109389). However, a recent meta-analysis in patients with type 1 or type 2 diabetes shows that improvements in insulin resistance may be clinically meaningful when compared with placebo (109389). In people with type 2 diabetes and nephropathy requiring hemodialysis, coenzyme Q10 120 mg orally daily for 12 weeks does not improve blood glucose levels, HbA1c, or lipid levels when compared with placebo, although it is associated with a decrease in serum insulin levels and insulin resistance (99636).
• Parkinson disease. Most clinical research does not show any benefit with the use of oral coenzyme Q10 in patients with Parkinson disease. Details: While some conflicting evidence exists (8938,15255), a large clinical trial and a meta-analysis of 8 small clinical studies in patients with Parkinson disease show that taking coenzyme Q10 300-2400 mg daily for up to 2 years does not improve Parkinson disease symptoms at any stage of the disease, or slow progression of the disease, when compared with placebo (89421,95610). In addition, a clinical study in patients with mid-stage Parkinson disease shows that taking a specific nanoparticulate coenzyme Q10 supplement (Nanoquinon, MSE Pharmazeutilka) 100 mg orally three times daily does not reduce symptoms when compared with placebo (15395).
• Post-polio syndrome. Muscle function in people with post-polio syndrome is not improved by oral coenzyme Q10. Details: Clinical research shows that taking coenzyme Q10 100 mg twice daily for 12 weeks does not improve muscle strength when compared with baseline, nor does it improve muscle function or muscle endurance when compared with placebo, in patients with post-polio syndrome (44054). Other clinical research shows that taking coenzyme Q10 100 mg daily for 60 days does not improve levels of fatigue when compared with placebo in patients with post-polio syndrome (97917).

LIKELY INEFFECTIVE

• Athletic performance. There is some evidence that exercise can deplete coenzyme Q10 and that supplementation will prevent this depletion. However, there is no evidence that taking coenzyme Q10 is beneficial. Details: Clinical research shows that taking coenzyme Q10 orally does not improve aerobic or anaerobic power or perceived exertion in athletes and non-athletes (2109,2110,8911,44122,44227). While some evidence suggests coenzyme Q10 slightly improves tolerance to higher workloads, more research is needed to tell if coenzyme Q10 is effective for this purpose (8911). One clinical study shows that taking coenzyme Q10 300 mg orally daily for 8 days reduces exercise-induced fatigue when compared with placebo (44006); other research shows that doses of 100-200 mg do not have this effect (44122,44233,44299). Taking the ubiquinol form of coenzyme Q10 200 mg orally daily for one month prevents exercise-induced coenzyme Q10 depletion and decreases levels of reactive oxygen species in blood mononuclear cells in young male athletes performing an intense long-distance run. However, it does not affect physical performance or markers of muscle damage (99429).
• Huntington disease. The ubiquinol form of coenzyme Q10 does not seem to improve function in people with this condition. Details: Ubiquinol, a reduced form of coenzyme Q10, has been evaluated for use in Huntington disease (11873). However, a large, high-quality study shows that taking coenzyme Q10 2.4 grams orally daily for up to 5 years does not slow the progression or functional decline in patients with Huntington disease (96538). Other studies using doses up to 600 mg daily also show no benefit (1357,8940).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related macular degeneration (AMD). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with early AMD shows that taking a specific combination product (Phototrop, Sigma-tau Health Science Ltd.) containing coenzyme Q10 10 mg, acetyl-L-carnitine 100 mg, and omega-3 fatty acids 530 mg orally daily for 12 months seems to reduce the percentage of patients who experience deterioration of vision by about 50%, and the percentage who have reduced light sensitivity by about 39%, when compared with placebo (43946). The effects of coenzyme Q10 alone are unclear.
• Aging. Although there has been interest in using oral coenzyme Q10 for aging, there is insufficient reliable information about the clinical effects of coenzyme Q10 for this purpose.
• Angina. There is some limited clinical evidence that coenzyme Q10 can improve exercise tolerance and symptoms in people with this condition. Details: Preliminary clinical research shows that taking coenzyme Q10 50 mg three times daily orally for 4 weeks improves exercise tolerance in people with angina by about 18% (2121). Also, taking 60 mg once daily for 4 weeks improves heart failure scores, angina symptoms, and heart volume when compared to baseline in patients with stable angina (44336). The validity of these findings is limited by the lack of a comparator group.
• Anthracycline cardiotoxicity. Evidence on the use of coenzyme Q10 to protect against anthracycline cardiotoxicity in adults and children is conflicting. Details: Preliminary clinical research in children aged 3-12 years shows that taking coenzyme Q10 orally 100 mg twice daily might protect against anthracycline cardiotoxicity (44279). However, evidence from larger clinical trials evaluating patients aged 16-77 years is conflicting. Results from one of these studies suggests that intravenous administration of coenzyme Q10 1 mg/kg daily the day before, the day of, and for 2 days after anthracycline treatment does not protect against cardiotoxicity (44267). Differences between the studies may be due to methodological problems, or differences in doses, route of administration, and age of participants.
• Asthma. Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of coenzyme Q10 (Q-Gel, Tishcon Corporation) 120 mg, vitamin E 400 mg, and vitamin C 250 mg orally daily in addition to conventional anti-asthmatic therapy for 16 weeks might reduce the dosage of corticosteroids required by patients with mild to moderate asthma. However, it does not appear to improve lung function any more than standard therapy alone (43969).
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral coenzyme Q10 is beneficial in children with ADHD. Details: A small clinical study in children aged 6-16 years with ADHD who are unresponsive to atomoxetine therapy shows that taking coenzyme Q10 1-3 mg/kg with atomoxetine 0.5-1.8 mg/kg daily for 6 months improves parent-rated symptoms of ADHD, particularly hyperactivity-related symptoms, when compared with placebo plus atomoxetine (107449).
• Autism spectrum disorder. It is unclear if the ubiquinol form of coenzyme Q10 taken orally is beneficial in children aged 3-6 years with this condition. Details: A small clinical study in children aged 3-6 years suggests that taking the reduced form of coenzyme Q10, ubiquinol (Li-QH, Tishcon Corporation), 50 mg orally once daily for one week followed by 50 mg twice daily for 11 weeks, improves symptoms of autism spectrum disorder, including communication with parents, ability to play with friends, verbal communication, sleeping, food rejection, aggressiveness, and self-harm, when compared with baseline, per parent assessment (89419). The validity of these findings is limited by the small study size, the use of parent assessment, and the lack of a comparator group.
• Benign prostatic hyperplasia (BPH). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with BPH shows that taking coenzyme Q10 100 mg plus L-carnitine daily for 8 weeks modestly decreases prostate volume and improves sexual performance when compared with placebo. There was no effect on prostate symptoms, prostate specific antigen levels, or quality of life. All patients were also taking finasteride 5 mg daily (113226). It is unclear if these effects are due to coenzyme Q10, L-carnitine, or the combination.
• Bipolar disorder. It is unclear if oral coenzyme Q10 is beneficial for bipolar disorder in older adults. Details: Preliminary clinical research in people 55 years of age or older with bipolar disorder shows that taking coenzyme Q10 800 mg orally daily for 4 weeks improves symptoms of depression when compared with baseline (95606). The validity of this finding is limited by the lack of a comparator group.
• Breast cancer. Low coenzyme Q10 levels may be associated with an increased risk of breast cancer. The benefit of coenzyme Q10 supplementation is unclear. Details: Population research in Chinese women has found that low plasma coenzyme Q10 levels are associated with an increased risk of breast cancer (44194).
• Cancer. Low coenzyme Q10 levels may increase the risk of cancer development and progression. Details: Population research has found that low coenzyme Q10 levels are associated with increased risk of metastatic melanoma (43959). Preliminary clinical research suggests that taking coenzyme Q10 150 mg twice daily along with vitamins A, C, and E, selenomethionine, beta-carotene, and folic acid extends survival time by 40% when compared with predicted survival in patients with end-stage cancer from various different primary sites (44159). It is unclear if this effect is due to coenzyme Q10, other ingredients, or the combination.
• Cardiovascular disease (CVD). It is unclear whether oral coenzyme Q10 has a role in preventing complications from CVD. Details: Preliminary clinical research shows that taking coenzyme Q10 300 mg 2 hours prior to an elective percutaneous coronary intervention does not reduce periprocedural myocardial injury or prevent major adverse cardiac events during one month of follow-up (96543). Other clinical research shows that taking a combination of coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg twice daily plus organic selenium yeast tablets (SelenoPrecise, Pharma Nord) 200 mcg daily for 4-5 years reduces the risk of death from CVD by 7% when compared with placebo in elderly people living in Sweden (92904). This benefit appears to persist even after supplement discontinuation, with an 18% reduction at 10 years and an 11% reduction at 12 years (96546,97466,97906). In this same trial, post-hoc subgroup analyses in patients with elevated baseline D-dimer levels and/or hypertension or ischemic heart disease shows that taking this combination reduces cardiovascular mortality when compared with placebo (105874). It is unclear if these benefits are due to coenzyme Q10, selenium, or the combination.
• Cataracts. It is unclear if coenzyme Q10-containing eye drops are beneficial in patients undergoing cataract surgery. Details: Clinical research suggests that administering an ophthalmic solution containing coenzyme Q10 and vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate twice daily for 9 months increases the speed of nerve regeneration when compared with saline solution in post-cataract surgery patients (44228).
• Cerebellar ataxia. It is unclear if coenzyme Q10 is beneficial for this condition. Details: Preliminary clinical research in patients with cerebellar ataxia shows that coenzyme Q10 30 mg/kg daily for 2 years improves ataxia scores by 48%, posture scores by 63%, and kinetic function scores by 37% when compared with baseline, but only in patients who are coenzyme Q10 deficient (44177). The validity of these findings is limited by the lack of a comparator group.
• Chronic fatigue syndrome (CFS). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with CFS shows that taking coenzyme Q10 200 mg plus NADH 20 mg daily for 8 weeks does not improve measures of fatigue, sleep, or quality of life when compared with placebo (107448).
• Chronic obstructive pulmonary disease (COPD). It is unclear if coenzyme Q10 is beneficial for improving exercise tolerance in people with COPD. Details: Preliminary clinical research suggests that taking coenzyme Q10 90 mg daily for 8 weeks reduces lactate production during anaerobic exercise in people with COPD, but does not improve oxygen consumption or exercise performance, when compared with baseline (44293). The validity of these findings is limited by the lack of a comparator group.
• Cocaine dependence. Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients with cocaine dependence shows that taking a combination of coenzyme Q10 200 mg and L-carnitine 500 mg orally daily for 8 weeks does not reduce cocaine use when compared with placebo, as measured by urine benzoylecgonine levels and self-reported usage (43940).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral coenzyme Q10 is beneficial for patients with persistent symptoms after COVID-19 infection. Details: Clinical research in individuals with previous confirmed COVID-19 infection and continued symptoms lasting more than 12 weeks shows that taking coenzyme Q10 (Pharma Nord) 100 mg five times daily for 6 weeks does not reduce the number or severity of symptoms when compared with placebo. The most common symptoms were concentration problems, mental and physical fatigue, headache, and/or muscle weakness (109392).
• Critical illness (trauma). It is unclear if oral coenzyme Q10 is beneficial in patients hospitalized due to acute trauma. Details: Preliminary clinical research in patients who are mechanically ventilated due to acute trauma and have low baseline coenzyme Q10 plasma levels shows that taking sublingual coenzyme Q10 (Nutri Q10, Nutri Century) 400 mg daily for 7 days reduces the duration of intensive care stay, mechanical ventilation, and hospitalization by 4 days, 2 days, and 6 days, respectively, when compared with placebo. Patients taking coenzyme Q10 also demonstrated larger improvements in organ function scores and coma scores than those taking placebo (105875).
• Cyclic vomiting syndrome (CVS). Limited evidence suggests oral coenzyme Q10 may reduce episodes of CVS. Details: Preliminary clinical research shows that taking coenzyme Q10 10 mg/kg orally twice daily is comparable to amitriptyline 0.5-1 mg/kg/day for reducing the number of CVS episodes in both children and adults (17703).
• Diabetic nephropathy. Although there has been interest in using oral coenzyme Q10 for diabetic nephropathy, there is insufficient reliable information about the clinical effects of coenzyme Q10 for this purpose.
• Dilated cardiomyopathy. Very small clinical studies suggest that children and adolescents with dilated cardiomyopathy may benefit from oral coenzyme Q10. Details: Preliminary clinical research in children with dilated cardiomyopathy suggests that taking coenzyme Q10 3-10 mg/kg daily, divided into 2-3 doses for up to 9 months, improves ejection fraction and New York Heart Association (NYHA) classification when compared to baseline (12199,13223). Also, in people under 20 years of age, taking a specific oral liquid formulation of coenzyme Q10 (QuinoMit Q10 Fluid, MSE Pharmazeutika GmbH), 10 mg/kg daily for 24 weeks produces a small increase in ejection fraction and improves NYHA class from II to I in 30% of patients (99427). The validity of these findings is limited by the lack of comparator groups.
• Dry eye. Ophthalmic coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research has evaluated the use of a specific eye drop (VisuXL, Visufarma) containing coenzyme Q10 and cross-linked hyaluronic acid, in a 1:1 ratio with alpha-tocopherol polyethylene glycol succinate. One study in menopausal women receiving antidepressants shows that placing 1 drop in each eye twice daily for 8 weeks reduces dry eye severity by 17% and improves tear break-up time when compared to 5 drops daily of carmellose eye drops (104553). In addition, another study in adults with mild to moderate dry eye shows that placing 1 drop in each eye four times daily for 12 weeks reduces dry eye severity by 14% and decreases some laboratory markers of dry eye when compared to hyaluronic acid alone. Both groups demonstrated similar improvement in meibomian gland function and tear break-up time (97909). The effect of coenzyme Q10 when used alone is unclear.
• Dry mouth. It is unclear if oral ubiquinol or ubiquinone improves salivary secretion. Details: Preliminary clinical research suggests that taking coenzyme Q10, as the reduced ubiquinol form or as the oxidized ubiquinone form, 100 mg orally daily for one month, improves salivary secretion by 72% to 82% when compared with baseline in patients with dry mouth (44191). The validity of these findings is limited by the lack of a comparator group.
• Erectile dysfunction (ED). It is unclear if oral coenzyme Q10 is beneficial in patients with ED. Details: A small, open-label study in patients with hypertension and complaints of ED shows that taking coenzyme Q10 200 mg daily for 3 months along with current antihypertensive therapy does not improve symptoms of ED when compared with antihypertensive therapy alone (107447).
• Fatigue. It is unclear if oral coenzyme Q10 is beneficial for reducing fatigue. Details: A meta-analysis of low- to moderate-quality clinical research in mixed populations shows that taking coenzyme Q10 modestly reduces feelings of fatigue when compared with placebo. This improvement was consistent between groups of healthy individuals and individuals with fatigue related to disease. However, a sub-group analysis shows that benefits are limited to studies in which coenzyme Q10 was studied as a single ingredient. Doses of coenzyme Q10 ranged from 60 mg to 500 mg daily for 4-12 weeks with treatment effects appearing to be both dose- and duration-dependent (109387).
• Friedreich ataxia. Oral coenzyme Q10 has been evaluated in combination with vitamin E; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking coenzyme Q10 (Bio-Quinon Q10, Pharma Nord) 200 mg orally twice daily plus vitamin E (Bio-E-Vitamin, Pharma Nord) 1050 IU twice daily for 47 months improves measures of cardiovascular function by 20% when compared with baseline. However, it does not improve posture or gait, or prevent deterioration of posture, gait, speech, or eye function, when compared with baseline (43943,44064). It is unclear if these benefits are due to coenzyme Q10, vitamin E, or the combination. Also, the validity of these findings is limited by the lack of a comparator group.
• Hearing loss. There is conflicting evidence regarding the effects of oral coenzyme Q10 on hearing loss of various etiologies. Details: Some clinical research shows that taking coenzyme Q10 terclatrate (Qter), a water-soluble formulation of coenzyme Q10, 160 mg orally daily for 30 days improves hearing thresholds when compared to baseline in patients with age-related hearing loss (44171,44184). However, taking coenzyme Q10 terclatrate 200 mg daily for 7 days does not significantly improve hearing thresholds when compared with placebo in patients with noise-induced hearing loss (44143). Also, combining coenzyme Q10 with conventional steroid therapy for 2 weeks does not improve hearing when compared with steroid therapy alone in patients with sudden sensorineural hearing loss (44185).
• Hepatitis C. It is unclear if oral coenzyme Q10 is beneficial in patients with this condition. Details: Clinical research shows that taking coenzyme Q10 up to 80 mg orally daily for 28 days does not reduce serum liver enzymes when compared with placebo in patients with chronic hepatitis C who are unresponsive to conventional treatment (44172).
• Hyperlipidemia. There is conflicting evidence regarding the effects of coenzyme Q10 on cholesterol levels in adults. However, any changes are unlikely to be clinically meaningful. Details: A meta-analysis of 50 moderate-quality clinical trials shows that taking coenzyme Q10 has small beneficial effects on levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides when compared with a control, usually placebo (109394). However, whether coenzyme Q10 produces clinically meaningful changes is unclear. In a subgroup of patients with dyslipidemia, coenzyme Q10 does not seem to have significant beneficial effects on total cholesterol (109394). Also, previous individual clinical trials and meta-analyses in specific populations, including studies in which lipoprotein A was measured, as well as populations with diabetes, coronary artery disease, and others, have not shown beneficial effects on plasma lipids (17704,44187,96545,97918,109394). The effect of coenzyme Q10 on lipoprotein A has also been investigated. Individual studies and a meta-analysis show that taking coenzyme Q10 slightly reduces plasma levels of lipoprotein A when compared with placebo (17704,44187,96545). Most studies have used doses of 100-500 mg daily for 4-24 weeks (17704,44187,96545,96547,97910,109394). Coenzyme Q10 has also been studied in combination with other ingredients. A moderate-sized, open-label clinical study in adults with mild hypercholesterolemia and low cardiovascular disease risk shows that taking a combination product containing coenzyme Q10 2 mg, red yeast rice, grape seed extract, olive tree leaf extract, and B vitamins (Arichol, Epsilon Health) daily for 8 weeks reduces total cholesterol and LDL cholesterol, but not HDL cholesterol or triglycerides, when compared with placebo (111559). The validity of this effect is limited by a lack of blinding. It is unclear if this effect is due to coenzyme Q10, other ingredients, or the combination.
• Hypertension. Most research suggests that oral coenzyme Q10 may reduce systolic blood pressure (SBP), but not diastolic blood pressure (DBP). Details: Most clinical research shows that taking coenzyme Q10 100-900 mg orally daily in divided doses, either alone or with conventional medications, for up to 12 weeks significantly lowers SBP (2122,3365,9890,17702,17650,17651,44343,109393). One meta-analysis of moderate quality clinical research in patients with cardiometabolic disorders shows that supplementation with coenzyme Q10, especially 100-200 mg daily for at least 12 weeks, reduces SBP by 5 mmHg (109393). However, some studies show conflicting results. Most clinical research shows that coenzyme Q10 supplementation does not reduce DBP (8907,96541,109393). Also, a meta-analysis of two clinical studies (17651,44211) shows that taking coenzyme Q10 100-200 mg orally daily has no significant effect on blood pressure when compared with placebo (95607). Conflicting results may be due to differences in the severity of hypertension at baseline, adjustments made to conventional medications during studies, and the presence of a variety of concomitant conditions. Some data also suggest that effects may be greater in people with low baseline levels of coenzyme Q10 (2122,17650,17651).
• Hypertrophic cardiomyopathy. It is unclear if oral coenzyme Q10 is beneficial for this condition. Details: A very small clinical study of 7 patients suggests that taking coenzyme Q10 (Vitaline) 120-240 mg orally daily with the goal of raising blood levels above 2 mcg/mL, might improve symptoms of hypertrophic cardiomyopathy, including dyspnea and fatigue, and decrease cardiac wall thickness, when compared to baseline (11031). The validity of these findings is limited by the small size of the study and the lack of a comparator group.
• Infertility. It is unclear if oral coenzyme Q10 helps women undergoing assisted reproductive technology (ART) treatment. Details: A meta-analysis of 5 small clinical studies in infertile women undergoing ART treatment shows that although coenzyme Q10 increases the odds of clinical pregnancy more than 2-fold, it does not seem to affect the rate of live births or miscarriages when compared with placebo or no treatment (103780).
• Kidney failure. Oral coenzyme Q10 has been reported to improve renal function in people with kidney failure, but not in those with less severe kidney disease. Details: Preliminary clinical research in patients with kidney failure shows that taking coenzyme Q10 180 mg orally daily for 28 days improves blood urea nitrogen, serum creatinine, and creatinine clearance when compared with placebo (44347). However, other clinical research in patients with less severe kidney disease shows that taking coenzyme Q10 200 mg daily for 8 weeks does not significantly improve kidney function parameters, including urinary albumin, total protein, or glomerular filtration rate, when compared with placebo (44128).
• Lichen planus. It is unclear if topical coenzyme Q10 is beneficial for oral lichen planus. Oral coenzyme Q10 has not been studied for this condition. Details: A small clinical study in patients with oral lichen planus conducted in Egypt shows that applying topical coenzyme Q10 (ubiquinol) 120 mg as a mucoadhesive tablet 3 times daily for 4 weeks does not improve pain scores or lesion size when compared with topical corticosteroid paste (111617).
• Male Infertility. Oral coenzyme Q10 may improve some measures of sperm function in males with infertility, but there is no convincing evidence that it can increase pregnancy rates. Details: One small clinical study in males with idiopathic asthenozoospermia shows that coenzyme Q10 200 mg orally daily for 6 months improves sperm motility when compared with baseline (12169). The validity of this finding is limited by the lack of a comparator group. Coenzyme Q10 has also been studied in males with idiopathic oligoasthenoteratozoospermia, but results are conflicting. Studies have used coenzyme Q10 or its reduced form, ubiquinol, in doses of 200-300 mg orally daily for 26 weeks. Sperm density and motility are increased when compared with placebo, but pregnancy rates do not seem to improve (17413,89422). Three studies have used coenzyme Q10 200-400 mg orally daily for 12-26 weeks, with two reporting increased sperm concentration and motility when compared to baseline, but the other finding no improvements when compared with placebo (44190,102008,107444). Coenzyme Q10 has also been investigated in combination with other ingredients. In one preliminary clinical trial, taking coenzyme Q10 10 mg and vitamin E 100 mg three times daily for 3 months modestly increases levels of testosterone and improves progressive sperm motility and morphology when compared with baseline. However, taking an L-carnitine nutrient complex 15 grams twice daily was more effective for increasing testosterone and for improving sperm parameters (109390). Other small and preliminary clinical studies have investigated the effects of a specific combination product providing coenzyme Q10 20 mg twice daily for 6 months, along with acetyl-L-carnitine, L-carnitine, selenium, zinc, vitamin C, folic acid, vitamin B12, and citric acid (Proxeed Plus). Taking this combination product has been shown to improve measures of sperm quality such as sperm count, sperm concentration, total motility, and progressive motility when compared to baseline. The effect on sperm volume and morphology is unclear. Most research has been conducted in patients with oligoasthenozoospermia, although some benefit has also been shown in patients with varicocele-related infertility, especially those with more severe varicocele (102017,107395,111296). The validity of these findings is limited by the lack of comparator group. Also, it is unclear if these effects are due to coenzyme Q10, other ingredients, or the combination.
• Maternally inherited diabetes mellitus and deafness (MIDD). It is unclear if oral coenzyme Q10 is beneficial for MIDD. Details: One small clinical study shows that taking coenzyme Q10 150 mg orally daily for 3 years might prevent progressive insulin secretory defect, exercise intolerance, and hearing loss when compared with baseline in people with this rare form of diabetes (2125).
• Metabolic syndrome. It is unclear if oral coenzyme Q10 is beneficial in patients with metabolic syndrome. Details: A small clinical study in patients with metabolic syndrome receiving healthy dietary recommendations shows that taking coenzyme Q10 60 mg daily for 12 weeks does not have beneficial effects on blood glucose, cholesterol, waist circumference, or blood pressure when compared with placebo (109284).
• Myocarditis. It is unclear if oral coenzyme Q10 is beneficial in patients with acute viral myocarditis. Details: A small observational study in Chinese patients with acute viral myocarditis has found that taking coenzyme Q10 10 mg and trimetazidine 20 mg three times daily for 2 weeks, along with standard care, is associated with higher rates of resolution and improved quality of life when compared with coenzyme Q10 plus standard care alone (107443). While coenzyme Q10 alone appeared to improve symptoms and markers of cardiac function when compared to baseline in some patients, the validity of these findings is limited by a lack of placebo control.
• Nonalcoholic fatty liver disease (NAFLD). Coenzyme Q10 may reduce liver enzymes and the severity of NAFLD. Details: Preliminary clinical research in adults with NAFLD shows that taking coenzyme Q10 100 mg orally daily for 12 weeks reduces the clinical grade of NAFLD and decreases plasma levels of liver enzymes when compared with placebo (97907).
• Obesity. Oral coenzyme Q10 does not seem to improve weight loss in adults. Details: A meta-analysis of small, highly heterogeneous clinical trials shows that taking coenzyme Q10 100-300 mg daily for up to 24 weeks does not reduce weight or body mass index when compared with placebo. However, the included studies were not designed to assess for weight loss and involved patients with type 2 diabetes, metabolic syndrome, kidney disease, liver disease, rheumatoid arthritis, and other conditions (105067).
• Periodontitis. Data on the effects of oral or topical coenzyme Q10 are conflicting. It is unclear if coenzyme Q10 is beneficial for periodontitis. Details: Some very small, low-quality studies suggest that taking coenzyme Q10 orally, 50 mg daily for 3 weeks, might be beneficial for periodontitis (8917,8918). Preliminary research with topical coenzyme Q10 suggests it is ineffective (2107,2108). However, a meta-analysis of 11 clinical trials evaluating coenzyme Q10 topical gel shows reductions in plaque index, bleeding index, pocket index, clinical attachment level, and gingival index when compared with placebo gel or scaling and root planing alone. The greatest effects are seen when coenzyme Q10 gel is applied directly into the periodontal pocket daily for at least six weeks in combination with scaling and root planing (108958). The validity of these findings is limited by a high risk of bias and the overall low quality of the included studies. Coenzyme Q10 has also been studied in combination with other ingredients for periodontitis. A small clinical study in patients with moderate or advanced periodontitis shows that taking a supplement containing 30 mg of coenzyme Q10 in addition to alpha-lipoic acid, cranberry extract, grapeseed extract, selenium, vitamin C, vitamin E, and zinc twice daily for 8 weeks in addition to standard nonsurgical therapy does not improve periodontal indices including bleeding on probing, gingival recession, plaque index, or inflammation, among others, when compared with placebo (111708).
• Physical performance. It is unclear if oral coenzyme Q10 improves physical performance in older adults with chronic kidney disease (CKD). Details: A small clinical study in mostly older adults with CKD shows that taking coenzyme Q10 1200 mg daily for 6 weeks does not improve measures of physical exercise endurance including aerobic capacity, total work, and work efficiency when compared with placebo (111558). The validity of these effects is limited by the small sample size and short study duration.
• Polycystic ovary syndrome (PCOS). Most clinical studies suggest that oral coenzyme Q10 modestly improves symptoms in patients with PCOS. Details: A meta-analysis of clinical trials in patients with PCOS shows that taking coenzyme Q10 modestly improves measures of glycemic response, as well as plasma lipids and some sex hormones, when compared with placebo (109384). However, any changes are small and the clinical relevance is unclear. Also, although nine studies were included in the review, the number of studies included for each endpoint was much lower. Most clinical studies included in the analysis used 100-200 mg daily for 8-12 weeks (107446,109384). An additional small clinical study also shows that taking coenzyme Q10 (Nature Made) 100 mg orally daily for 12 weeks reduces fasting plasma glucose, insulin, and total cholesterol and improves insulin sensitivity when compared with placebo. This study also found that taking coenzyme Q10 reduces alopecia by about 33% and acne by 48% when compared with placebo (97914). Another small clinical study shows that taking coenzyme Q10 100 mg daily for 12 weeks reduces depression, anxiety, and hirsutism when compared with placebo (107446).
• Prader-Willi syndrome (PWS). It is unclear if oral coenzyme Q10 is beneficial in patients with PWS. Details: Preliminary clinical research in children with Prader-Willi syndrome shows that taking coenzyme Q10 2.5 mg/kg orally daily for one year improves psychomotor development similarly to growth hormone therapy, although this might reflect natural changes in the condition occurring over time (44005).
• Pre-eclampsia. Taking coenzyme Q10 orally seems to reduce the rate of pre-eclampsia in women at risk for the condition. Details: Clinical research shows that taking coenzyme Q10 (Q-absorb, Jarrow Formulas) 100 mg orally twice daily during pregnancy, starting at 20 weeks gestation and continuing until term, reduces the rate of pre-eclampsia by about 44% when compared with placebo in women at risk for developing this condition (17201).
• Schizophrenia. It is unclear if oral coenzyme Q10 improves symptoms in patients with schizophrenia or schizoaffective disorder. Details: A small clinical study in patients with schizophrenia or schizoaffective disorder shows that taking coenzyme Q10 300 mg daily for 6 months does not improve attention, working memory, negative symptoms, mood disorders, or quality of life when compared with placebo (105069). This finding is limited by insufficient power and poor protocol adherence, with only 61% of the participants taking at least 90% of the study treatment.
• Sepsis. There is no strong evidence that coenzyme Q10 is helpful in the management of sepsis or septic shock. Details: Patients with septic shock have been shown to have low levels of coenzyme Q10, but the effects of supplementation are unclear. Some preliminary clinical research shows that taking coenzyme Q10 100 mg orally twice daily for 7 days reduces the risk of in-hospital mortality by 69% and improves markers of inflammation, but does not reduce length of ICU stay, when compared with conventional treatment alone (102548). However, other preliminary research shows that taking coenzyme Q10 as ubiquinol 200 mg twice daily for 7 days has no effect on inflammatory or vascular endothelial biomarkers, mortality, or length of stay when compared with placebo (96540). Both studies were small and likely underpowered to detect a meaningful change in clinical outcomes.
• Statin-induced myalgia. There is conflicting evidence regarding the effects of oral coenzyme Q10 on statin-associated muscular adverse effects, such as myalgia. Details: Some clinical research shows that taking coenzyme Q10 (Q-Sorb softgel, Nature's Bounty) 100 mg orally daily for 30 days reduces pain intensity when compared with baseline or vitamin E control in patients with statin-induced myalgia (16008,44345). Other clinical research shows that taking coenzyme Q10 (MGC Company) 50 mg orally twice daily for 30 days reduces muscle pain and pain interference with daily activities by 30% to 40% when compared with placebo (95604). One small study in adults with statin-induced myalgia shows that taking liquid coenzyme Q10 (Q-Factor, Giellepi S.p.A) 100 mg orally daily for 3 months modestly reduces pain scores, but not plasma creatine kinase (CK) levels, when compared with placebo (102007). Other clinical research shows that taking coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg twice daily, with or without selenium, for 3 months, reduces muscle pain and weakness, cramps, and tiredness when compared with placebo (92909). However, not all studies have shown benefit. Meta-analyses of several small randomized controlled trials show that taking coenzyme Q10 100-600 mg daily for 1-3 months does not improve muscle pain, statin tolerability, or plasma CK activity in patients with statin-induced myalgia when compared with placebo (95602,103781,106050). However, the validity of these results is limited by small population size and high heterogeneity. Other clinical research shows that taking coenzyme Q10 60 mg twice daily for 3 months does not improve muscle pain when compared with placebo (44218). Also, taking coenzyme Q10 (Q-Gel, Tishcon Corporation) 200 mg daily for 12 weeks does not affect myalgia scores when compared with placebo in patients taking simvastatin (44346). Additionally, taking high doses of coenzyme Q10 600 mg daily for 8 weeks does not affect the incidence, severity, or time to onset of statin-induced myalgia when compared with placebo in patients taking simvastatin (95603). Reasons for these conflicting findings are not entirely clear. The inconsistent results do not appear to be related to the dose of coenzyme Q10 or plasma CK levels. About 50% of patients who experience statin-induced myalgia will tolerate a statin re-challenge with a lower or equivalent dose of the same or alternative statin after a statin-free interval, which is a higher response rate than seen in currently available studies with the use of coenzyme Q10. Taking coenzyme Q10 for 30 days may be a reasonable option if other attempts to improve tolerance have failed. If a significant improvement in pain related to statin use is not seen after 30 days of taking coenzyme Q10, it is unlikely to be beneficial (96548).
• Statin-induced myopathy. There is conflicting evidence regarding the effects of coenzyme Q10 on statin-associated muscular adverse effects, including myopathy. Details: Clinical research shows that taking coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg orally twice daily, with or without selenium, for 3 months, reduces muscle weakness and pain, cramps, and tiredness when compared with placebo in patients with statin-induced myopathy due to atorvastatin, fluvastatin, rosuvastatin, or simvastatin (92909). Preliminary clinical research also shows that taking coenzyme Q10 60 mg orally four times daily decreases the rate of dose-limiting statin-induced myopathy in patients taking high-dose lovastatin as an investigational treatment for cancer (11899,11900). However, when coenzyme Q10 (Myoquinon, Pharma Nord,) 400 mg orally daily is used in combination with selenium for 12 weeks, it does not affect atorvastatin-induced myopathy when compared with placebo (92908).
• Toxin-induced liver damage. Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients being treated with anti-tuberculosis drugs shows that taking coenzyme Q10 200 mg, acetyl-L-carnitine 250 mg, and alpha-lipoic acid 250 mg twice daily for 2 weeks reduces the risk of drug-induced liver injury by 73% when compared with placebo (107445). It is unclear if these findings are due to coenzyme Q10, other ingredients, or the combination.
• Ulcerative colitis. It is unclear if oral coenzyme Q10 is beneficial in patients with ulcerative colitis. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking oral coenzyme Q10 (Nutri Q10, Nutri Century Company) 100 mg twice daily for 8 weeks modestly improves ulcerative colitis disease activity and quality of life scores when compared with placebo. Taking coenzyme Q10 also reduces systolic and diastolic blood pressure by 4 mmHg and 2 mmHg, respectively, when compared with placebo (106049). The clinical relevance of these changes is unclear.
• Wrinkled skin. It is unclear if topical application of coenzyme Q10 cream can reduce wrinkles. Details: A small clinical study shows that applying a coenzyme Q10 1% cream to the skin twice daily for 5 months reduces objective wrinkle scores when compared to baseline (44082). The validity of this finding is limited by the lack of a comparator group. More evidence is needed to rate coenzyme Q10 for these uses.

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LIKELY SAFE ...when used orally or intravenously and appropriately. Calcium is safe when used in appropriate doses (7555,12928,12946,95817). However, excessive doses should be avoided. The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: Age 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg; 19-50 years, 2500 mg; 51+ years, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stone, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients not to consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).

POSSIBLY UNSAFE ...when used orally in excessive doses. The National Academy of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 19-50 years, 2500 mg; 51 years and older, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients to not consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Calcium is safe when used in appropriate doses (17506).

CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses. The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately (945,1586,3263,3264,17506). The World Health Organization (WHO) recommends prescribing oral calcium supplementation 1.5-2 grams daily during pregnancy to those with low dietary calcium intake to prevent pre-eclampsia (97347).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses. The Institute of Medicine sets the same daily tolerable upper intake level (UL) for calcium according to age independent of pregnancy status: 9-18 years, 3000 mg; 19-50 years, 2500 mg (17506). Doses over these amounts might increase the risk of neonatal hypocalcemia-induced seizures possibly caused by transient neonatal hypoparathyroidism in the setting of excessive calcium supplementation during pregnancy, especially during the third trimester. Neonatal hypocalcemia is a risk factor for neonatal seizures (97345).

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LIKELY SAFE ...when used orally and appropriately. Coenzyme Q10 has been used safely in studies lasting up to 5 years (2134,6037,6038,6407,8163,8938,8939,8940,15395,17413,17716,96538)(109391). ...when used topically on the gums (2107,2108,8916,8917,8918).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Coenzyme Q10 in doses of 1-10 mg/kg/day has been used safely for up to 9 months under medical supervision (12199,13223,15256,44005,107449).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Coenzyme Q10 100 mg twice daily has been used with apparent safety during pregnancy, starting at 20 weeks gestation until term (17201).

LACTATION:
Insufficient reliable information available; avoid using.

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ALUMINUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.  Details Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease (21631). However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption (93006).

BISPHOSPHONATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Calcium reduces the absorption of bisphosphonates.  Details Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates (12937).

CALCIPOTRIENE (Dovonex) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Taking calcipotriene with calcium might increase the risk for hypercalcemia.  Details Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia (12938). Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.

CALCIUM CHANNEL BLOCKERS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.  Details Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects (6124). But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers (12939,12947).

CEFTRIAXONE (Rocephin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.  Details Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction (15794,21632). So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.  Details Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin (12940). However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin (38960).

DILTIAZEM (Cardizem, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, calcium may reduce the therapeutic effects of diltiazem.  Details Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.

DOLUTEGRAVIR (Tivicay) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Calcium seems to reduce levels of dolutegravir.  Details Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation (93578).

ELVITEGRAVIR (Vitekta) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Calcium seems to reduce levels of elvitegravir.  Details Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation (94166).

LEVOTHYROXINE (Synthroid, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Calcium seems to reduce the absorption and effectiveness of levothyroxine.  Details Advise patients to take levothyroxine and calcium supplements at least 4 hours apart. Calcium reduces levothyroxine absorption, probably by forming insoluble complexes (5082). Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroidism (5081,5082,6137).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.  Details Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients (38953). Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Calcium seems to reduce the absorption of quinolone antibiotics.  Details Advise patients to take oral quinolones at least 2 hours before or 4-6 hours after calcium supplements or calcium-fortified foods. Taking calcium at the same time as oral quinolones can reduce quinolone absorption. Calcium binds to quinolones in the gut (4412,10339,21638,38570).

RALTEGRAVIR (Isentress) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Calcium may reduce levels of raltegravir.  Details Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir (94164). However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure (94165).

SOTALOL (Betapace) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Calcium seems to reduce the absorption of sotalol.  Details Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes (10018).

TETRACYCLINE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Calcium seems to reduce the absorption of tetracycline antibiotics.  Details Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut (1843).

THIAZIDE DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.  Details Thiazides reduce calcium excretion by the kidneys (1902). Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.

VERAPAMIL (Calan, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, calcium may reduce the therapeutic effects of verapamil.  Details Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.

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ALKYLATING AGENTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.  Details Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy (5158,5159). The clinical importance of this interaction is unknown.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.  Details Some clinical research shows that coenzyme Q10 can significantly lower blood pressure (2122,3365,8907,9890,17702,17650,17651,44343,96541), although other studies have shown conflicting results (17651,44211,95607).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.  Details Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin (2128,6048,6199). Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported (2128,6048,11048). However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR (11905).

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General ...Orally and intravenously, calcium is well-tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Belching, constipation, diarrhea, flatulence, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about calciphylaxis and kidney stones.

Cardiovascular ...There has been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these results, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Reasons for these discrepancies are not entirely clear. It may relate to whether calcium is taken as monotherapy or in combination with vitamin D. When taken with vitamin D, which is commonly recommended, calcium supplementation does not appear to be associated with an increased risk of CVD, CHD, or MI (93533,107231). Also, the association between calcium supplementation and CVD, CHD, or MI risk may be influenced by the amount of calcium consumed as part of the diet. Supplementation with calcium may be associated with an increased risk of MI in people with dietary calcium intake above 805 mg daily, but not in those with dietary calcium intake below 805 mg daily (17482). To minimize the possible risk of CVD, CHD, or MI, advise patients not to consume more than the recommended daily intake of 1000-1200 mg and to consider total calcium intake from both dietary and supplemental sources (17484). While dietary intake of calcium is preferred over supplemental intake, advise patients who require calcium supplements to take calcium along with vitamin D, as this combination does not appear to be associated with an increased risk of MI (93533).
Rarely, calcium intake can increase the risk of calciphylaxis, which usually occurs in patients with kidney failure. Calciphylaxis is the deposition of calcium phosphate in arterioles, which causes skin ulcers and skin necrosis. In a case report, a 64-year-old female with a history of neck fracture, sepsis, and ischemic colitis presented with painful leg ulcers due to calciphylaxis. She discontinued calcium and vitamin D supplementation and was treated with sodium thiosulfate and supportive care (95816).

Gastrointestinal ...Orally, calcium can cause belching, flatulence, nausea, gastrointestinal discomfort, and diarrhea (1824,1843,12950,38803). Although constipation is frequently cited as an adverse effect of calcium, there is no scientific substantiation of this side effect (1824,1843,1844,1845,12950,38978). Calcium carbonate has been reported to cause acid rebound, but this is controversial (12935,12936).

Oncologic ...There is some concern that very high doses of calcium might increase the risk of prostate cancer. Some epidemiological evidence suggests that consuming over 2000 mg/day of dietary calcium might increase the risk for prostate cancer (4825,12949). Additional research suggests that calcium intake over 1500 mg/day might increase the risk of advanced prostate cancer and prostate cancer mortality (14132). Consumption of dairy products has also been weakly linked to a small increase in prostate cancer risk (98894). However, contradictory research suggests no association between dietary intake of calcium and overall prostate cancer risk (14131,14132,104630). More evidence is needed to determine the effect of calcium, if any, on prostate cancer risk.

Renal ...Kidney stones have been reported in individuals taking calcium carbonate 1500 mg daily in combination with vitamin D 2000 IU daily for 4 years (93943).

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General ...Orally, coenzyme Q10 is generally well tolerated. In clinical studies, no serious adverse effects have been reported.
Most Common Adverse Effects:
Orally: Gastrointestinal side effects such as appetite suppression, diarrhea, epigastric discomfort, heartburn, nausea, and vomiting. These generally occur in less than 1% of patients. Some of these adverse effects can be minimized if daily doses above 100 mg are divided.

Cardiovascular ...Palpitations have been reported as being possibly associated with coenzyme Q10 treatment (89421). Death due to myocardial infarction occurred in one Parkinson disease patient taking coenzyme Q10; causality is unclear (15395).

Dermatologic ...Two of 143 participants in a case series reported skin itching after starting treatment with oral coenzyme Q10 (6047). Allergic rash has also been reported (6409,11872). An itching exanthema was seen in two heart failure patients treated with intravenous coenzyme Q10 (44284).

Gastrointestinal ...Gastrointestinal side effects of coenzyme Q10 have included nausea (3365,6409,8907,10152,43982,44172,44179,44330,89421,109392), vomiting (3365,10152,44330,89421), epigastric discomfort (3365,44179,44330,89421), constipation (109392), diarrhea (44179,92904,89421,109392), stomach upset (8940,12170,109387,109388,109392), loss of appetite (2121), heartburn (2121,44179,109392), and flatulence (43982), although this occurs in less than 1% of patients. In one clinical study, gastrointestinal bleeding in association with angiodysplasia has been reported to be possibly related to coenzyme Q10 treatment (89421).

Genitourinary ...An uncomplicated urinary infection was reported in a patient taking oral coenzyme Q10 (nanoQuinon, MSE Pharmazeutika) (44020).

Hematologic ...Thrombocytopenia was noted in one patient treated with oral coenzyme Q10 (44296); however, other factors (viral infection, other medications) may have been responsible for this adverse effect.

Musculoskeletal ...Increased plasma creatine kinase with high-intensity exercise has been reported in patients taking coenzyme Q10 (44303). Muscle pain has been reported rarely in one clinical trial (109392).

Neurologic/CNS ...Headache and dizziness have been reported in human research (3365,11872,43982,44330,109392). Insomnia has been reported as being possibly associated with coenzyme Q10 treatment (89421). Cognitive decline, depression, and sudden falls were reported rarely in a clinical trial of patients with Huntington disease (8940). Increased lethargy was reported for one patient treated with oral coenzyme Q10 (44042). Feeling of internal trembling has been reported in a clinical trial for one patient treated with coenzyme Q10 (44020).

Ocular/Otic ...Visual sensitivity to light has been reported for a patient treated with coenzyme Q10. However, the association of this effect with coenzyme Q10 treatment was not clear (6409).
A burning sensation has been reported for 10% of patients treated with a topical eye solution containing coenzyme Q10 and alpha-tocopheryl polyethylene glycol 1000 succinate following cataract surgery (44228).

Psychiatric ...Worsening depression has been reported as being possibly associated with oral coenzyme Q10 treatment (89421).

Pulmonary/Respiratory ...Drug-induced pneumonitis was diagnosed in a 61 year-old woman who had been taking coenzyme Q10 and perilla leaf extract for two months (43978). Symptoms improved after she stopped taking the supplements and began taking oral prednisone. Causation from coenzyme Q10 was unclear.

Other ...In a case report, a naval aviator using a supplement containing coenzyme Q10 and niacin had reduced G tolerance (44186). G tolerance was regained with cessation of the supplement.

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