Alpha Sun Capsules by Cell Tech International

POSSIBLY EFFECTIVE

• Hypertension. Oral blue-green algae seem to modestly reduce blood pressure in patients with hypertension. Details: Some small clinical studies show that blue-green algae can decrease blood pressure in patients with hypertension (97206,99654). A meta-analysis of five small clinical trials in patients with hypertension, type 2 diabetes, or chronic pain shows that taking spirulina blue-green algae 1-8 grams daily for up to 12 weeks reduces systolic blood pressure (SBP) by 5 mmHg and diastolic blood pressure (DBP) by 7 mmHg when compared with placebo. The effect size was larger in patients with hypertension and in those treated for at least 12 weeks (109964). Another small clinical study shows that taking spirulina blue-green algae (A. maxima) 4.5 grams daily for 6 weeks decreases blood pressure in adults with hypertension, with the number of subjects fulfilling the criteria for hypertension decreasing from 45% to 14% when compared to baseline (18297). A more recent clinical study in patients with hypertension shows that consuming a salad dressing containing 2 grams spirulina blue-green algae daily for 8 weeks reduces SBP by around 6 mmHg and DBP by around 4 mmHg when compared to baseline. While overall reduction in blood pressure with spirulina dressing was larger when compared with patients consuming a control dressing, the study groups were heterogenous at baseline, limiting the validity of any statistical comparisons between groups (109965).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral blue-green algae are beneficial in allergic rhinitis. Details: Preliminary clinical research shows that taking spirulina blue-green algae (A. platensis) 2 grams daily for 6 months, improves self-rated scores for sneezing, nasal discharge, nasal congestion, and itching when compared with placebo in adults with allergic rhinitis (18300).
• Antiretroviral-induced insulin resistance. It is unclear if oral blue-green algae are beneficial for insulin resistance due to antiretrovirals. Details: Preliminary clinical research shows that taking spirulina blue-green algae (A. platensis) 19 grams daily for 2 months increases insulin sensitivity by about 225% when compared to baseline in patients with antiretroviral-induced insulin resistance (75944). The validity of this finding is limited by the lack of a comparator group.
• Anxiety. Although there has been interest in using oral blue-green algae for anxiety, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Arsenic poisoning. It is unclear if oral blue-green algae are beneficial for chronic arsenic toxicity. Details: Preliminary clinical research in people living in areas of Bangladesh with high arsenic levels in drinking water shows that taking a combination of an alcoholic extract of spirulina blue-green algae 250 mg and zinc 2 mg orally twice daily for 16 weeks, in addition to use of filtered drinking water, increases urinary arsenic excretion, reduces hair arsenic levels, and improves skin manifestations of chronic arsenic toxicity when compared with placebo plus filtered water (18301).
• Athletic performance. Most research suggests that oral blue-green algae are not beneficial for improving athletic performance; however, the available studies are small. Details: AAlthough some research disagrees, most small or preliminary clinical trials show that taking spirulina blue-green algae does not improve athletic performance in trained or untrained adults. One study shows that, when compared with placebo, taking spirulina blue-green algae (Hawaiian Spirulina, Cyanotech Corporation) 3 grams daily for up to 8 weeks has no effect on exercise output during a 30-minute elliptical trainer workout in active males (97203). In elite rugby players, taking spirulina blue-green algae (Algae Green Value) 5.7 grams daily for 7 weeks does not improve jump or sprint performance or body composition when compared to placebo (104567). In healthy untrained males, a small study shows that taking spirulina blue green algae 6 grams daily for 7 days does not increase the time to fatigue related to arm cycling following a 30-minute submaximal exercise bout (104566). In male recreational runners, spirulina blue-green algae (A. platensis) 2 grams three times daily for 4 weeks was not associated with any change in exercise intensity during a 2-hour treadmill jogging period. However, sprinting time to exhaustion following the 2-hour jog increased from 2.05 minutes to 2.7 minutes (18306). Also, a study of athletes and non-athletes shows that taking spirulina blue-green algae (Parry Nutraceuticals) 2 grams daily for 8 weeks has a small effect on isometric muscle strength, but not muscle endurance, when compared with placebo (104568).
• Attention deficit-hyperactivity disorder (ADHD). Oral blue-green algae have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking 3 mL of a specific combination of spirulina blue-green algae, peony, ashwagandha, gotu kola, bacopa, and lemon balm (Nurture and Clarity, Tree of Healing-LD) diluted in 50-60 mL of water three times daily for 4 months improves ADHD scores when compared with placebo in previously untreated children aged 6-12 years (19272). It is unclear if this effect is due to blue-green algae, other ingredients, or the combination.
• Beta-thalassemia. It is unclear if oral blue-green algae are beneficial in beta-thalassemia. Details: In children with beta-thalassemia, preliminary clinical research shows that taking spirulina blue-green algae (GNC Natural Brand Spirulina, General Nutrition Corporation) 250 mg/kg daily, up to a maximum dose of 4 grams daily, for 3 months reduces the percentage of children requiring blood transfusion during an interval of less than 2 weeks from 66% to 40%. There were also improvements in red blood cell count and levels of hemoglobin, ferritin, and liver function enzymes (104569). However, the validity of these findings is limited by the lack of a comparator group.
• Blepharospasm. It is unclear if oral blue-green algae are beneficial when used in conjunction with botulinum toxin injections. Details: Preliminary clinical research shows that taking a specific product containing the blue-green algae species Aphanizomenon flos-aquae (Super Blue-Green Algae, Cell Tech) 1500 mg per day orally for 6 months in addition to botulinum toxin-A injections does not reduce eyelid spasms when compared with botulinum toxin-A alone in people with essential blepharospasm or Meige syndrome (14842).
• Cancer. Although there has been interest in using oral blue-green algae for cancer, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Cardiovascular disease (CVD). Although there has been interest in using oral blue-green algae for CVD, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Cognitive Impairment. It is unclear if oral blue-green algae are effective for improving cognitive impairment. Details: A small clinical study in patients aged 60 or older with mild cognitive impairment shows that taking blue-green algae extract 1 gram 3 times daily for 12 weeks slightly improves some components of cognitive function testing related to visual learning, memory, and vocabulary when compared with placebo (112001). However, the validity of these findings is limited by lack of adjustment for multiple comparisons, which may explain the discrepant results with the other components of the cognitive function tests.
• Depression. Although there has been interest in using oral blue-green algae for depression, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Diabetes. It is unclear if oral blue-green algae are beneficial in diabetes. Details: A meta-analysis of seven small clinical studies in patients with type 2 diabetes shows that taking spirulina blue-green algae 0.8-14 grams daily for 6-12 weeks reduces fasting blood glucose and improves total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol, but does not affect low-density lipoprotein (LDL) cholesterol, when compared with placebo. There was no reduction in glycated hemoglobin (HbA1c); however, all but two of the studies lasted less than 12 weeks, limiting the validity of the findings related to HbA1c (109970).
• Dyslipidemia. It is unclear if oral blue-green algae are beneficial in dyslipidemia. Details: Several clinical studies in patients with normal or elevated cholesterol levels show that doses of spirulina blue-green algae (A. platensis, A. maxima, A. fusiformis) ranging from 1-10 grams daily for 1-6 months may reduce total cholesterol by 8% to 27%, low-density lipoprotein (LDL) cholesterol by 10% to 65%, and triglycerides by 0% to 23%; and increase high-density lipoprotein (HDL) cholesterol by 0% to 66% (18297,18298,18299,91705,91708,91710,91717,102689). However, the validity of these studies is limited by methodological weaknesses and heterogeneous population characteristics. A meta-analysis of 23 small studies, several of which were in patients with type 2 diabetes or obesity, shows that taking blue-green algae 0.8-10 grams for 4 to 24 weeks modestly improves levels of LDL, HDL, triglycerides, and total cholesterol when compared with placebo or no treatment (112004). The interpretation of these findings is limited by the high heterogeneity of the included studies which enrolled patients of varying health status and employed various study designs.
• Dyspepsia. Although there has been interest in using oral blue-green algae for dyspepsia, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Exercise-induced muscle soreness. It is unclear if oral blue-green algae are effective for the prevention of exercise-induced muscle soreness. Details: A small clinical study in recreationally trained males shows that taking spirulina blue-green algae 2 grams three times daily does not reduce delayed onset muscle soreness after eccentric exercise when compared with placebo (109967).
• Hepatitis C. Evidence for the use of oral blue-green algae in hepatitis C is conflicting. Details: One clinical study in adults with chronic hepatitis C who are unresponsive to interferon treatment shows that taking spirulina blue-green algae (A. platensis) 500 mg orally three times daily for 6 months is associated with greater improvements in alanine aminotransferase (ALT) levels than taking silymarin 140 mg three times daily. Complete virological response rates were 13% with blue-green algae and 3% with silymarin, although this difference was not statistically significant (63247). However, in another study in people with chronic hepatitis B or C, liver function enzyme levels worsened after one month of treatment with oral spirulina blue-green algae (18304).
• HIV/AIDS. It is unclear if oral blue-green algae are beneficial for people with HIV/AIDS who do not have access to antiretrovirals. Details: One clinical study in adults with untreated HIV shows that taking spirulina blue-green algae (A. platensis) powder 5-10 grams daily for 3-6 months does not affect CD4 counts, viral load, or weight gain in patients with HIV (75927,91707). However, in one study, the incidence of opportunistic infections, respiratory disease, gastrointestinal symptoms, and fatigue was 43% for patients taking spirulina blue-green algae, compared to 70% for patients taking placebo (91707).
• Iron deficiency anemia. Although there has been interest in using oral blue-green algae for iron deficiency anemia, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Lichen planus. It is unclear if oral blue-green algae are beneficial in patients with oral lichen planus. Details: A small clinical study in patients with oral lichen planus shows that taking spirulina blue-green algae 500 mg twice daily for 8 weeks along with application of triamcinolone acetonide 0.1% oral paste three times daily for 1 week reduces pain and lesion size when compared with only triamcinolone acetonide three times daily for 8 weeks (109963).
• Malnutrition. Evidence for the use of oral blue-green algae in malnutrition is conflicting. Details: Some clinical research in severely undernourished children shows that adding spirulina blue-green algae (A. platensis) 5 grams orally twice daily for 8 weeks to a traditional diet results in an average daily weight gain of 25 grams, compared with only 15 grams for those given the traditional diet alone. Similarly, giving blue-green algae 10 grams twice daily for 8 weeks in addition to a misola diet (millet, soy, peanut kernel, sugar, and salt) results in an average daily weight gain of 34 grams, compared with only 20 grams for children given the misola diet alone (18308). However, a small clinical study in malnourished children aged 3 months to 3 years shows that giving spirulina blue-green algae 5 grams daily for 3 months in addition to a traditional diet fails to increase weight gain more than the traditional diet alone (18309). Similarly, a moderate-size crossover study in preschool-aged children in Cambodia shows that taking blue-green algae 2 grams 5 times a week during the first hour of school for 8 weeks does not improve weight gain or height but may reduce the proportion of children with anemia when compared with placebo (112002). The interpretation of these findings is limited by the high rate of patients lost to follow-up and the lack of statistical adjustment for confounding factors, such as parasitism and home diet.
• Memory. Although there has been interest in using oral blue-green algae for memory, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Menopausal symptoms. It is unclear if oral blue-green algae are beneficial for improving symptoms of menopause. Details: A preliminary clinical study shows that taking a product containing the blue-green algae species Aphanizomenon flos-aquae (Klamin, Nutrigea) 1.6 grams daily for 8 weeks reduces anxiety and depression when compared with placebo in menopausal adults aged 50-60 years. The treatment has no effect on vasomotor symptoms or hormone levels (18310).
• Mental alertness. It is unclear if oral blue-green algae are beneficial for reducing mental fatigue. Details: A preliminary clinical study shows that taking spirulina blue-green algae (Hawaiian Spirulina, Cyanotech Corporation) 3 grams daily for up to 8 weeks improves performance on a mathematical based mental fatigue test in healthy men when compared with placebo. Subjective improvement in mental alertness over placebo was also reported (97203).
• Metabolic syndrome. It is unclear if oral blue-green algae are beneficial in patients with metabolic syndrome. Details: A small clinical study in patients with metabolic syndrome shows that taking spirulina blue-green algae (Spirulysat, AlgoSource), providing phycocyanin 20 mg, daily for 12 weeks improves triglyceride levels, but does not reduce body mass index, waist circumference, blood pressure, glycemic indices, or other lipid levels, when compared with placebo (109971).
• Nonalcoholic fatty liver disease (NAFLD). Although there has been interest in using oral blue-green algae for NAFLD, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Obesity. Evidence for the use of blue-green algae in obesity is conflicting. Details: Small, low-quality clinical trials have shown mixed results in people with obesity (18295,91717,97205,99655,99703,102688). When results are analyzed together, there is evidence of a very small benefit for both body weight and plasma lipid levels. Two meta-analyses show that taking spirulina blue-green algae may increase weight loss by up to 1.85 kg when compared with placebo (102690,104565). A greater effect is seen in patients with obesity when compared with overweight patients. In addition, there is a small effect on fat loss (102690). However, there is evidence from two studies lasting longer than 12 weeks that taking blue-green algae may slightly increase BMI (104565). A meta-analysis of small clinical trials also shows that taking spirulina blue-green algae reduces fasting blood sugar and total cholesterol levels by a small amount when compared with placebo, but has no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels, in patients with obesity (102689). When combined with an exercise program, taking spirulina blue-green algae increases weight loss by 1.4 kg and improves exercise tolerance and total, LDL, and high-density lipoprotein (HDL) cholesterol levels when compared with exercise alone (99655,102688). Doses have included a specific product containing the spirulina blue-green algae species A. fusiformis (Multinal, New Ambadi Estate Pvt. Ltd.) 1 gram twice daily or four times daily for 3 months (91717) or spirulina blue-green algae 2 grams daily for 3 months, or 4.5 grams daily for 6 weeks, alone or in combination with exercise (97205,99655,102688).
• Oral leukoplakia. It is unclear if oral blue-green algae are beneficial for oral leukoplakia in tobacco chewers. Details: Preliminary clinical research shows that taking spirulina blue-green algae (A. fusiformis) orally 1 gram daily for 12 months produces regression of precancerous oral leukoplakia lesions in 45% of tobacco chewers, compared to only 7% of those receiving placebo. Regression rates appear to be highest in those with homogeneous lesions and lowest in those with ulcerated or nodular lesions (15782).
• Periodontitis. It is unclear if injecting blue-green algae into periodontal pockets is beneficial in periodontitis. Details: Preliminary clinical research shows that injecting a 4% w/v gel prepared from spirulina blue-green algae into periodontal pockets of adults with chronic periodontitis, after scaling and root planing, is associated with a decrease in probing pocket depth of 1.57 mm after 120 days, compared with only 0.84 mm in patients receiving scaling and root planing alone (91709).
• Premenstrual syndrome (PMS). Although there has been interest in using oral blue-green algae for PMS, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Stress. Although there has been interest in using oral blue-green algae for stress, there is insufficient reliable information about the clinical effects of blue-green algae for this condition.
• Ulcerative colitis. It is unclear if oral blue-green algae are beneficial in patients with ulcerative colitis. Details: A small clinical study in patients with ulcerative colitis shows that taking spirulina blue-green algae 500 mg twice daily for 8 weeks improves quality of life scores and reduces stress and sleep disturbances when compared with placebo. However, there was no effect on most measures of sleep quality, mood, and fatigue (109969).
• Wound healing. Although there has been interest in using oral blue-green algae for wound healing, there is insufficient reliable information about the clinical effects of blue-green algae for this condition. More evidence is needed to rate blue-green algae for these uses.

(Read more about BLUE-GREEN ALGAE)

EFFECTIVE

• Hemorrhagic disease. Oral or intramuscular vitamin K1 is effective for preventing hemorrhagic disease in newborns. Details: Vitamin K1 (phytonadione) administered orally or intramuscularly can prevent classic hemorrhagic disease of newborns (15,85367,85484). A single intramuscular administration of vitamin K1 1 mg is considered to be the most effective method, while oral administration of three doses of vitamin K1 1-2 mg over 8 weeks is considered to be an acceptable alternative (85506). The effects of vitamin K on late hemorrhagic disease of newborns is less clear (85367,85484). In the Netherlands, an oral dose of 25 mcg daily for 3 months was used until 2011, when it was increased to 150 mcg daily. A reduction of late intracranial vitamin K deficiency bleeding in the general pediatric population, from 1.6 per 100,000 to 1.3 per 100,000, was associated with this dose increase (102351).
• Hypoprothrombinemia. Oral or parenteral vitamin K1 is effective for treating and preventing hypoprothrombinemia. Details: Vitamin K1 (phytonadione) 2.5-25 mg, used orally or parenterally, can prevent and treat hypoprothrombinemia caused by vitamin K deficiency or induced by salicylates, sulfonamides, quinine, quinidine, or broad-spectrum antibiotic therapy (15).
• Vitamin K-dependent clotting factors deficiency (VKCFD). Oral and intravenous vitamin K1 is the primary treatment for VKCFD. Details: Oral supplementation with vitamin K 10 mg two to three times weekly seems to prevent major hemorrhages and reduce mucocutaneous bleeding in individuals with VKCFD. Also, intravenous vitamin K may improve the prothrombin time-international normalized ratio (PT-INR) values in these patients. While vitamin K supplementation is the primary treatment method for VKCFD, the response to treatment varies significantly (85481).
• Warfarin anticoagulation. Oral and intravenous vitamin K1 reverse warfarin-related excessive anticoagulation. Evidence for the use of oral vitamin K1 in patients with an unstable INR is conflicting. Details: Taking vitamin K1 (phytonadione) orally or parenterally, but not subcutaneously, can counteract excessive warfarin anticoagulation and restore therapeutic international normalized ratio (INR) levels. Usually a single dose of 1-5 mg is used (85406,85425,85429). Vitamin K might also be effective for stabilizing warfarin anticoagulation in patients with low intake of vitamin K. Patients with a low dietary vitamin K intake are significantly more likely to have an unstable INR than those who ingest higher amounts of vitamin K (16803). It is thought that vitamin K-depleted patients become more sensitive when vitamin K is ingested, even in small quantities, resulting in erratic or unstable INR (16804). One small clinical study and one small retrospective chart review show that taking oral vitamin K1 (phytonadione) 100-150 mcg daily improves INR stability in patients taking warfarin who previously had an unstable INR (16805,16806). However, a larger clinical study found no significant differences in INR stability in patients taking vitamin K 100 mcg daily when compared with placebo (16807). Also, some research suggests that, although taking vitamin K 1250 mcg daily may reduce INR in patients with excessive warfarin anticoagulation more significantly than placebo, there may not be a significant difference in the risk of bleeding complications (23380). It is important to keep in mind that, if a patient is stabilized on warfarin therapy plus vitamin K supplementation, discontinuing vitamin K can significantly increase the INR within 2-3 weeks after discontinuation (17714). The most recent guidelines by the American College of Chest Physicians do not recommend routine use of vitamin K supplementation for patients on warfarin therapy with unstable INR (94926). However, the previous guidelines recommended vitamin K 100-200 mcg daily for these patients. Therefore, some providers still use vitamin K for this purpose (16808).

POSSIBLY EFFECTIVE

• Osteoporosis. Oral vitamin K might reduce the risk of fractures and bone loss in patients with osteoporosis. However, it may not be beneficial in patients at risk for developing osteoporosis. Details: Although observational and clinical research on dietary and supplemental vitamin K for osteoporosis has been conflicting (14364,85392,85445,102354), overall, vitamin K supplementation seems to slightly reduce fracture risk (102354). A meta-analysis combining data from 36 heterogeneous studies in osteoporotic or postmenopausal patients shows that taking different regimens of either vitamin K1 or vitamin K2 is associated with a small reduction in clinical fractures (from 3.1% to 2.2%), but not with changes in vertebral fractures or BMD when compared with control (102354). This analysis is limited by the high variability in study designs and a lack of subgroup analyses stratifying different patient populations and forms of vitamin K. An older meta-analysis of 19 clinical studies in osteoporotic or postmenopausal patients shows that taking vitamin K2 (menaquinone) 45 mg, primarily used in the MK-4 form, daily does not reduce the risk of fractures when compared with control, although there was a non-significant trend towards a reduction (91451). A sensitivity analysis that excluded the largest negative study of over 4000 postmenopausal Japanese females with mild osteoporosis (85456), showed that vitamin K2 45 mg daily reduces the risk of fractures by 53% and improves lumbar and vertebral BMD in patients with osteoporosis when compared with control (91451). This effect was not seen in patients without osteoporosis (91451). Vitamin K2 also does not seem to benefit patients with osteopenia. A recent clinical trial in postmenopausal patients with osteopenia shows that taking a larger dose of vitamin K2 (375 mcg, MK-7) with calcium 800 mg and vitamin D 1500 IU daily for 3 years does not seem to affect BMD, bone turnover, or bone microarchitecture when compared with placebo (105035). Vitamin K1 (phytonadione) has also been evaluated, with mixed findings. One clinical study in postmenopausal patients with osteopenia shows that taking vitamin K1 5 mg daily with calcium 1500 and vitamin D 800 IU for up to 4 years reduces clinical fractures, but does not reduce clinical fragility fractures or improve BMD, when compared with placebo and vitamin D with calcium (85453). In healthy, non-osteoporotic patients ages 60-80 years, one clinical study shows that taking vitamin K1 500 mcg daily with calcium 600 mg and vitamin D 400 IU for 3 years does not affect BMD, despite increased plasma vitamin K levels and reduced undercarboxylated osteocalcin concentrations, when compared with taking calcium and vitamin D alone (16404). The same null effect on BMD and a reduced undercarboxylated osteocalcin was shown in a small clinical study in patients with Crohn disease without osteoporosis, taking vitamin K1 1-2 mg in combination with vitamin D3 400 IU and calcium 500 mg daily for 12 months (91454).

POSSIBLY INEFFECTIVE

• Intraventricular hemorrhage. Oral vitamin K does not reduce the risk of periventricular hemorrhage in preterm infants. Details: A meta-analysis of results from clinical research shows that administering vitamin K to pregnant patients at risk for very preterm birth does not reduce the overall risk of periventricular hemorrhage in preterm infants, perinatal mortality, or the associated neurological injury by the age of 7 years when compared to control. A subgroup analysis shows that vitamin K might reduce the risk of severe periventricular hemorrhage by 42% in preterm infants. However, when trials with inadequate blinding were excluded, this result was not statistically significant (85469).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. It is unclear if oral vitamin K2 improves athletic performance. Details: A small clinical study shows that taking vitamin K2 (menaquinone) 320 mcg orally daily for 4 weeks followed by 160 mg daily for 4 weeks, increases maximal cardiac output by 12% when compared with placebo in trained athletes performing standardized cycle ergometer exercise tests (95937).
• Beta-thalassemia. Oral vitamin K2 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking the menaquinone-7 (MK-7) form of vitamin K2 50 mcg daily plus vitamin D3 (calcitriol) 5 mcg daily for 12 months modestly improves bone mineral density (BMD) at the lumbar spine when compared to baseline in children with beta-thalassemia aged 3-18 years (91456). It is not clear if this improvement can be attributed to vitamin K, vitamin D3, or the combination.
• Breast cancer. It is unclear if dietary intake of vitamin K2 reduces the risk of breast cancer. Details: Population research has found that higher dietary intake of vitamin K2 (menaquinone) or vitamin K1 (phytonadione) is not associated with a reduced risk of premenopausal or postmenopausal breast cancer (85474).
• Cancer. It is unclear if dietary intake of vitamin K reduces the risk of cancer or cancer-related mortality. Details: One large population study involving healthy German patients has found that consuming more than 42-46 mcg of vitamin K2 (menaquinone) daily is associated with a 27% reduced risk of cancer mortality, but not cancer incidence, when compared with consuming less than 23-26 mcg daily. Dietary intake of vitamin K1 (phytonadione) was not associated with the risk of cancer or cancer mortality (85474). Another population study involving Mediterranean patients at high risk for cardiovascular disease has found that consuming about 630 mcg of vitamin K1 daily is associated with a 46% lower risk of cancer mortality when compared with consuming about 171 mcg of vitamin K1 daily. However, higher dietary intake of vitamin K2, 87 mcg daily, was not associated with a lower risk of cancer mortality when compared to those with lower dietary intake (79 mcg daily) (91452). Reasons for these discrepancies may relate to the definitions for high and low intake, the use of different databases to calculate vitamin K intake, and the different populations studied.
• Cardiovascular disease (CVD). It is unclear if dietary or supplemental vitamin K reduces the risk of CVD events; the available research is conflicting. Details: Most population research, including a meta-analysis of 21 observational cohort studies, has found that dietary intake of vitamin K1 (phytonadione) or vitamin K2 (menaquinone) is not associated with reduced risk for most cardiovascular events, such as CVD mortality, nonfatal MI, or stroke, although there might be a slightly reduced risk for CHD (85414,85482,91452,102353,103922). However, some population studies have found benefit. Observational research in a Danish cohort aged 50-65 years with no history of atherosclerotic cardiovascular disease at baseline shows that those in the highest quintile of dietary vitamin K1 intake have a 21% lower risk of CVD-related hospitalization and complications, such as ischemic heart disease, ischemic stroke, or peripheral artery disease, over 17-22 years when compared with the lowest quintile of intake. This inverse association tapers off at intakes above 100 mcg daily. For vitamin K2 intake, the highest quintile has a 14% lower risk of hospitalization when compared with the lowest quintile, although the association is U-shaped, indicating an increased risk at high doses. The researchers theorize that this may be due to the fact that vitamin K2-rich foods include cheese, eggs, and butter (109910,109920). There is also interest in using vitamin K to slow aortic valve calcification (AVC) and coronary artery calcification (CAC), which are CVD risk factors. In healthy patients ages 60-80 years with pre-existing CAC, taking a multivitamin with vitamin K1 (phytonadione) 500 mcg orally daily for 3 years reduces CAC progression by 6% when compared with the multivitamin alone (85461). However, research in patients with AVC has found no benefit. One small clinical study in patients on hemodialysis shows that taking the menaquinone-7 form of vitamin K2, 200 mcg orally daily for 1 year, does not affect the rate of AVC progression when compared with placebo (102352). Also, clinical research in males with significant AVC shows that taking the menaquinone-7 form of vitamin K2 720 mcg and vitamin D 25 mcg orally daily for 2 years does not reduce the rate of AVC progression or the rate of cardiovascular events, heart valve surgery, or all-cause mortality when compared with placebo (109916).
• Cataracts. It is unclear if dietary vitamin K reduces the risk of cataracts in older adults. Details: A secondary analysis of results from clinical research has found that higher dietary vitamin K1 (phytonadione) intake over a mean 5.6 years' follow-up is associated with a lower risk of cataracts and a lower incidence of cataract surgery in older adults at high risk for cardiovascular disease. The hazard ratio for developing cataracts was 0.71 and the hazard ratio for cataract surgery was 0.75 for people in the highest tertile of dietary vitamin K1 intake when compared with the lowest tertile (95936).
• Cognitive impairment. It is unclear if dietary vitamin K alters the rate of decline in adults with cognitive impairment. Details: Clinical research in adults aged 55-75 years with overweight or obesity, metabolic syndrome, and cognitive impairment shows that the largest increases in dietary vitamin K intake over a 2-year period are linked to a slower rate of cognitive decline when compared with the lowest increases in intake. This is demonstrated by higher scores on the mini-mental state examination (MMSE) and verbal fluency tests, and a greater number of patients maintaining an MMSE score of at least 24 (109919).
• Colorectal cancer. It is unclear if dietary intake of vitamin K2 reduces the risk of colorectal cancer. Details: Population research has found that higher dietary intake of vitamin K2 (menaquinone) or vitamin K1 (phytonadione) is not associated with a reduced risk of colorectal cancer (85474).
• Cystic fibrosis. It is unclear if oral vitamin K improves coagulopathy in patients with cystic fibrosis. Details: Suboptimal vitamin K status is common in patients with cystic fibrosis, especially those with pancreatic insufficiency, due to problems with fat digestion (85359,85479). Preliminary clinical research in patients with cystic fibrosis shows that taking vitamin K 1-5 mg orally for one month might decrease osteocalcin levels when compared with baseline, which suggests a lower risk of bone fractures (103920). Also, a small clinical trial in adults and children with cystic fibrosis and pancreatic insufficiency shows that taking a supplement containing fat-soluble vitamins A, D, E, and K for an average of 8.6 months reduces the number of patients with abnormal levels of protein induced by vitamin K absence (PIVKA-II), a defective form of prothrombin (85374).
• Depression. It is unclear if dietary intake of vitamin K reduces depression. Details: Population research has found that a dietary intake of vitamin K greater than 232 mcg daily is associated with reduced odds of depressive symptoms when compared with intakes of less than 83 mcg daily in older adults who are not taking vitamin D supplements. For every 100 mcg increase in vitamin K intake per day, the study found an 18% reduction in odds of depressive symptoms. However, there was no association identified in individuals taking vitamin D (100181). The effect of vitamin K for the prevention or treatment of clinical depression has not been investigated.
• Diabetes. It is unclear if oral vitamin K1 improves glycemic control in patients with diabetes. Details: A small clinical study in patients with diabetes who are taking oral antidiabetes medications shows that taking vitamin K2 (MK-7) 180 mcg twice daily for 12 weeks seems to reduce glycated hemoglobin by 1.6%, compared with a slight increase in the placebo group (105034). This study is limited due to high dropout rate in the placebo group.
• EGFR inhibitor-induced acneiform rash. It is unclear if topical vitamin K is beneficial for the treatment or prevention of acneiform rash caused by EGFR inhibitors. Details: Preliminary clinical research in adults receiving treatment with cetuximab, an EGFR inhibitor, shows that applying vitamin K1 (phytonadione) 0.1% cream (Vigorskin, Merck Serono SpA) twice daily to the face and trunk for 12 weeks may modestly reduce the percentage of patients who develop a moderate to severe acneiform rash (91455). The validity of this finding is limited by the lack of a control group. In patients with an existing rash after receiving the EGFR inhibitors cetuximab and panitumumab, a small clinical study shows that applying vitamin K1 (phytonadione) 1% ointment twice daily for 8 weeks to half of the affected area does not reduce the number of acneiform eruptions when compared with using placebo ointment on the other half of the affected area (103919). Patients in this study were allowed to use concomitant antibiotics and moisturizing agents, which may have confounded the results.
• Kidney failure. It is unclear if oral vitamin K2 reduces the incidence or severity of muscle cramps in adults with kidney failure. Details: Preliminary clinical research in patients on maintenance hemodialysis for at least 3 months with treatment-resistant muscle cramps shows that taking the menaquinone form of vitamin K2 360 mcg orally daily for 8 weeks reduces the frequency, severity, and duration of muscle cramps when compared with placebo (109917).
• Kidney transplant. It is unclear if vitamin K is beneficial for reducing cardiovascular risk in kidney transplant recipients. Details: Preliminary clinical research in adults with a stable kidney transplant for at least 1 year shows that taking vitamin K (menadiol diphosphate) 5 mg orally three times weekly for 1 year does not reduce aortic stiffness or coronary artery calcification, which are markers of cardiovascular disease, when compared with placebo (109913). The effects of long-term supplementation are unclear.
• Liver cancer. Small clinical studies suggests that vitamin K2 reduces mortality and the risk for hepatocellular carcinoma recurrence. Details: Meta-analyses of 9-11 small clinical trials in patients with resectable hepatocellular carcinoma show that adding vitamin K2 45 mg daily for up to 3 years seems to reduce cancer recurrence by 9.5% and reduce the risk of mortality by 7% when compared with control. Meta-analyses of 3-4 small clinical trials in patients with non-resectable carcinoma show that taking vitamin K2 45 mg for up to 2 years seems to reduce cancer recurrence by 3% and reduce mortality by 16% when compared with control (105032). Most of the included studies were conducted in Japan, so it is unclear if these results are generalizable to other geographic locations.
• Liver disease. It is unclear if dietary intake of vitamin K reduces the risk of liver disease. Details: A small observational study in patients with chronic liver failure due to cholestatic liver disease has found that receiving intramuscular vitamin K1 10 mg daily for an average of 16 days is associated with a lower risk of death when compared with control (103926).
• Lung cancer. It is unclear if dietary intake of vitamin K reduces the risk of lung cancer. Details: Population research has found that consuming greater than 42-46 mcg of vitamin K2 (menaquinone) daily is associated with a 62% lower risk of lung cancer occurrence and a 59% lower risk of lung cancer mortality when compared to those who consume less than 23-26 mcg of vitamin K2 daily. Dietary intake of vitamin K1 (phytonadione) is not associated with a reduced risk of lung cancer or lung cancer mortality (85474).
• Multiple sclerosis (MS). It is unclear if topical vitamin K reduces cutaneous adverse effects of MS treatment. Details: In patients with relapsing-remitting MS, burning and pain can accompany subcutaneous interferon treatment. Preliminary clinical research shows that topical application of vitamin K cream (dose not specified) for 8 weeks reduces burning by approximately 8% and pain by 9% when compared with no prophylactic treatment. Redness of the skin is also reduced with vitamin K (91453).
• Overall mortality. It is unclear if dietary intake of vitamin K reduces overall mortality. Details: Observational research in healthy older adults has found that serum vitamin K levels 0.5 nmol/L or less, which corresponds to consuming about 50% of the recommended vitamin K adequate intake, is associated with a 19% higher risk of overall mortality when compared with higher serum levels of vitamin K (103922). In a Danish cohort of adults with a median age of 56 years at baseline, the comparative risk for all-cause mortality between the highest and lowest quintiles of K1 intake over a period of 17-23 years was 0.76. The risk for cardiovascular mortality was 0.72, and the risk of cancer-related mortality in smokers or former smokers, specifically, was 0.8. However, the correlation tapered off above a daily intake of 100 mcg (109911).
• Pancreatic cancer. It is unclear if dietary intake of vitamin K reduces the risk of pancreatic cancer. Details: Observational research in over 100,000 Americans aged 55-74 years at baseline has found no association between dietary vitamin K2 intake and pancreatic cancer incidence over an average follow-up of 9 years. However, the hazard ratio for development of pancreatic cancer was 0.57 for the highest quintile of dietary vitamin K1 intake when compared with the lowest quintile (109912).
• Polycystic ovary syndrome (PCOS). It is unclear if vitamin K improves PCOS symptoms. Details: Small clinical study in patients with PCOS show that taking vitamin K2 (menaquinone-7) 90 mcg daily for 8 weeks does not reduce fasting blood glucose, acne, hirsutism, or weight, although it improves depression and seems to reduce fasting insulin, when compared with placebo (105036,109918).
• Prostate cancer. It is unclear if dietary intake of vitamin K reduces the risk of prostate cancer. Details: Population research has found that higher dietary intake of vitamin K2 (menaquinone), but not vitamin K1 (phytonadione), is associated with a reduced risk of prostate cancer, particularly advanced prostate cancer (85443,85474).
• Rheumatoid arthritis (RA). It is unclear if oral vitamin K improves RA symptoms. Details: One small clinical study in patients with RA shows that adding the MK-7 form of vitamin K2 (menaquinone) 100 mcg daily to treatment with conventional antirheumatic agents for 3 months improves disease activity and inflammatory markers when compared with antirheumatic agents alone. When compared to the control group, vitamin K2 reduced disease activity scores by 41% (91449). However, another small clinical study in patients with mild to moderate RA shows that taking vitamin K1 (phytonadione) 10 mg daily for 8 weeks with conventional antirheumatic agents does not improve disease activity or inflammatory markers when compared with placebo (100182). These contrasting outcomes may be related to the type of vitamin K used, the duration of treatment, and the severity of the illness.
• Rosacea. Although there is interest in using topical vitamin K1 for rosacea, there is insufficient reliable information about the clinical effects of vitamin K for this condition.
• Stroke. It is unclear if dietary intake of vitamin K1 reduces the risk of stroke. Details: Population research has found that higher dietary intake of vitamin K1 is not associated with a reduced risk of stroke (85482).
• Wound healing. Although there is interest in using topical vitamin K1 for wound healing, there is insufficient reliable information about the clinical effects of vitamin K for this condition. More evidence is needed to rate vitamin K for these uses.

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POSSIBLY SAFE ...when non-contaminated species of spirulina blue-green algae are used orally and appropriately (91713). The blue-green algae species Arthrospira platensis has been used with apparent safety in doses up to 19 grams daily for 2 months, or 10 grams daily for 6 months (18296,18300,18306,75944,91705,99703,104567,109965). The blue-green algae species Arthrospira fusiformis has been used with apparent safety in doses up to 4 grams daily for 3 months, or 1 gram daily for 12 months (15782,91717). Another blue-green algae species, Arthrospira maxima, has been used with apparent safety in a dose of 4.5 grams daily for up to 12 weeks (18297,99654,99655,102688). ...when non-contaminated, non-toxin producing strains of blue-green algae from the Aphanizomenon flos-aquae species are used orally and appropriately. Doses up to 1.6 grams daily have been used with apparent safety for up to 6 months (14842,18310). Some blue-green algae species can produce toxins called microcystins. According to the World Health Organization (WHO), the tolerable daily intake of microcystins in adults is 0.04 mcg/kg (96549).

POSSIBLY UNSAFE ...when contaminated blue-green algae are used orally. Blue-green algae can be contaminated with heavy metals (including mercury, cadmium, lead, or arsenic), neurotoxins, and toxic microcystin-producing cyanobacteria such as Microcystis aeruginosa (9171,75966,91704,91711,96550). Microcystins are most commonly reported in the blue-green algae species Aphanizomenon flos-aquae harvested from Upper Klamath Lake in Oregon. The Oregon Department of Health has set a limit of 1 mcg of microcystin-LR equivalents per gram dry weight of blue-green algae, assuming consumption of about 2 grams/day by adults (91704,91713). However, many samples of Aphanizomenon flos-aquae have been reported to contain higher levels than this (9171,91704). According to the World Health Organization (WHO), the tolerable daily intake of microcystins in adults is 0.04 mcg/kg (96549). When consumed orally, microcystins accumulate in the liver, binding to and inhibiting protein phosphatases, causing hepatocyte damage and possible tumor promotion (9171). Aphanizomenon flos-aquae can also produce neurotoxic compounds that may be present in supplements containing this organism (91704).

CHILDREN: POSSIBLY UNSAFE
when blue-green algae products are used orally. Blue-green algae can accumulate heavy metals such as lead and mercury (91704,91711). They can also contain toxic microcystins produced by contaminating species of cyanobacteria such a Microcystis aeruginosa (91704). Children are more sensitive to poisoning by microcystins (3536). The Oregon Department of Health has set a limit for microcystins of 1 mcg per gram dry weight of blue-green algae, but some countries have set very low exposure limits of 0.2 mcg per day and 0.8 mcg per day for infants and children, respectively (91704).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using. Some blue-green algae products, specifically those of the species Aphanizomenon flos-aquae, have been found to contain low amounts of beta-methylamino-L-alanine (BMAA). BMAA is associated with neurodegenerative diseases, and breast milk has been shown to be a potential source of BMAA exposure in infants (96550).

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LIKELY SAFE ...when vitamin K1 (phytonadione) or vitamin K2 (menaquinone) is used orally and appropriately. Vitamin K1 up to 10 mg daily and vitamin K2 up to 45 mg daily have been safely used in clinical trials lasting up to 2 years. A tolerable upper intake level for vitamin K in adults has not been set (54,55,58,6799,7135,14364). ...when vitamin K1 (phytonadione) is used parenterally and appropriately. Vitamin K1 (phytonadione) in oral and injectable form is an FDA-approved drug (7135).

POSSIBLY SAFE ...when vitamin K1 (phytonadione) 0. 1% is used topically in a cream or ointment for up to 12 weeks (91455,103919).

CHILDREN: LIKELY SAFE
when vitamin K1 (phytonadione) is used orally or parenterally and appropriately. Vitamin K1 (phytonadione) in oral and injectable form is FDA approved for use in children. A tolerable upper intake level for vitamin K in children has not been set (7135).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts that do not exceed the daily adequate intake level (AI). A tolerable upper intake level for vitamin K in pregnancy and lactation has not been set (7135).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, spirulina blue-green algae might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs. However, this is unlikely.  Details Spirulina blue-green algae have shown antiplatelet and anticoagulant effects in vitro (18311,18312,75892,92162,92163). However, one preliminary study in 24 patients receiving spirulina blue-green algae 2.3 grams daily for 2 weeks showed no effect on platelet activation or measures of clotting time (97202).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking blue-green algae with antidiabetes drugs might increase the risk of hypoglycemia.  Details Human research shows that spirulina blue-green algae can have hypoglycemic effects in patients with diabetes, at least some of whom were using antidiabetes drugs (18299). However, blue-green algae does not seem to improve glycated hemoglobin (HbA1c) levels in patients with diabetes (102689,109970). A meta-analysis of animal studies also suggests that spirulina blue-green algae have hypoglycemic effects (109970).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of blue-green algae might interfere with immunosuppressive therapy.  Details Blue-green algae have been shown to stimulate the immune system (2534,10267).

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WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = C Vitamin K can antagonize and reverse the therapeutic effects of warfarin.  Details Vitamin K antagonizes the effects of warfarin (15,23380,25507,25508,85425,85429). Excessive vitamin K intake, either from supplements or from changes in the diet, can reduce the anticoagulant effect of warfarin (15).

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General ...Orally, spirulina blue-green algae seem to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, bloating, diarrhea, dizziness, fatigue, flatulence, headache, nausea, and vomiting.

Dermatologic ...Orally, a severe rash has been reported in a 49-year-old woman after taking a spirulina blue-green algae supplement (species and dose unknown). After stopping the supplement, inflammatory myopathy with muscle weakness and elevated creatine kinase occurred. The condition resolved with corticosteroid and cyclophosphamide treatment (75936). In another case report, an 82 year-old woman developed a blistering skin condition over a 2-year period while taking spirulina blue-green algae (A. platensis, dose unknown). She had partly hemorrhagic bullae, secreting erosions and macerations. These symptoms resolved when the supplement was stopped and the patient was treated with oral prednisone, topical silver sulfadiazine, and topical triamcinolone / neomycin (75921).

Gastrointestinal ...Orally, gastrointestinal complaints are amongst the most common adverse effects associated with spirulina blue-green algae, including nausea, vomiting, diarrhea, and abdominal cramps (19272,75924,91713,109969). Similarly, common adverse effects associated with the blue-green algae species Aphanizomenon flos-aquae are stomach upset, flatulence, diarrhea, and bloating (14842).

Hematologic ...Orally, three cases of mild gum bleeding and one case of mild bruising have been reported in patients taking spirulina blue-green algae (Cyactiv, Cerule LLC) 2. 3 grams daily (containing approximately 1 gram of phycocanin) for 2 weeks (97202).

Hepatic ...Orally, significant elevations of liver function tests within 2 weeks of starting a spirulina blue-green algae supplement (species and dose unknown) have been reported in a 52-year-old man stabilized on amlodipine, simvastatin, and acarbose. A biopsy showed feathery degeneration and ballooning of hepatic cells. Cholestasis was present, and an ex-vivo lymphocyte stimulation test for spirulina blue-green algae was positive. All drugs and the spirulina blue-green algae supplement were stopped, with return of the LFTs to normal (9172).

Immunologic ...Orally, urticarial rashes and pruritus have occurred as part of generalized allergic reactions to blue-green algae (91706,91711,91712).
In one case report, a 14-year-old male experienced anaphylaxis with urticaria, lip edema, and asthma 6 hours after taking five tablets of spirulina blue-green algae (A. platensis, strength unknown). He had a positive skin prick test. Oral challenge to an extract of the tablets, and IgE from his serum, reacted with the beta chain of C-phycocyanin from A. platensis (91712).
In another case report, a 17-year-old male with a history of multiple allergies developed rash, pruritus, angioedema, wheezing, and dyspnea within 10 minutes of taking spirulina blue-green algae (A. platensis) 300 mg. He had a positive skin test to A. platensis but no other ingredients of the tablets (91706).

Musculoskeletal ...Orally, after a 49-year-old woman stopped taking a spirulina blue-green algae supplement (species and dose unknown), the patient experienced inflammatory myopathy with muscle weakness and elevated creatine kinase. The condition resolved with corticosteroid and cyclophosphamide treatment (75936). Another case report describes acute rhabdomyolysis that occurred after consumption of spirulina (Arthrospira platensis, Hawaiian spirulina, Solgar Inc., Leonia, NJ) 3 grams daily for 1 month. The 24-year old man presented with weakness, myalgias, elevated creatine kinase and liver function tests, and myoglobinuria (75922).

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General ...Orally, vitamin K is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, nausea, and stomach upset.
Serious Adverse Effects (Rare):
Intravenously: There have been rare cases of anaphylaxis and hyperbilirubinemia (in infants).

Dermatologic ...Orally, intake of vitamin K2 (menaquinone) along with calcium and vitamin D3 can cause an increased incidence of skin and skin appendage lesions compared to taking calcium and vitamin D3 alone. However, the risk of this adverse event is low, with 0.5 incidences per 100 patient-years occurring for patients treated with vitamin K, calcium, and vitamin D3 and 0.1 incidences per 100 patient-years occurring for patients treated with calcium and vitamin D3 alone (85467).

Gastrointestinal ...Orally, vitamin K can cause mild to moderate gastrointestinal side effects (91450,91451). The most common effects include nausea, abdominal pain, and diarrhea (91450,91451).

Hepatic ...Orally, vitamin K3 (menadione) has been linked to hepatotoxicity. Vitamin K3 is no longer used therapeutically in North America because it has been linked to hepatic toxicity and jaundice in animal research (7135).

Other ...Intravenously, vitamin K can cause reactions that resemble hypersensitivity or anaphylaxis (85389). These reactions are rare. It is unclear whether the adverse effect is caused by the drug or a component of the solution. There have been very rare cases of hyperbilirubinemia, particularly in premature neonates, following large doses of vitamin K (15).

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