Arginine by Higher Nature

POSSIBLY EFFECTIVE

• Angina. Oral L-arginine seems to improve symptoms and exercise tolerance in patients with angina. Details: Clinical research shows that taking L-arginine orally seems to decrease symptoms and improve exercise tolerance and quality of life in patients with mild to severe angina (3593,7815,7816,31866,31923). Some patients with severe angina who have frequent attacks at rest despite treatment with standard antianginal agents might also benefit from L-arginine (3593). However, L-arginine does not seem to improve objective measures of blood vessel dilation or increase circulating concentrations of nitric oxide (7817,99262). Also, when used in combination with ten 200 mcg injections of vascular endothelial growth factor (VEGF)-165 plasmid DNA, L-arginine 6 grams daily orally for 3 months does not improve angina severity in patients with coronary artery disease who underwent surgical angiogenesis compared to patients who did not receive this combination (32001). In addition, intravenous infusion of arginine 10% solution does not improve exercise capacity in patients with stable angina when compared with placebo (31843,32293).
• Erectile dysfunction (ED). Oral L-arginine might improve symptoms of ED. When taken with phosphodiesterase type 5 (PDE5) inhibitors, L-arginine seems to provide a small additional benefit. Details: Taking L-arginine orally in high doses, 5 grams daily, improves subjective assessment of sexual function in males with organic ED when compared with placebo (222,102586). Additionally, a meta-analysis of 4 small clinical studies in patients with ED, including those with diabetes and/or cardiovascular disease risk factors, shows that although PDE5 inhibitors improve sexual function better than L-arginine, the combination of PDE5 inhibitors and L-arginine may be more effective than either treatment alone (105065). In most clinical trials, doses of L-arginine 2.5-5 mg daily for 6-12 weeks were used alone or in addition to PDE5 inhibitors such as sildenafil 50 mg or tadalafil 5-10 mg daily (102586,102587,102592,104222). Higher doses have also been investigated. One clinical trial shows that taking L-arginine (Bioarginina, Farmaceutici Damor S.p.A., Napoli, Italy), 2 grams three times daily for 3 months improves sexual function compared with placebo (110387). However, taking lower doses, 1.5 grams daily, might not be effective in patients with mixed-type ED (2038). L-arginine has also been examined in combination with other ingredients. Some preliminary clinical evidence suggests that taking L-arginine orally in low doses, 1.7 grams daily in combination with maritime pine bark extract (Pycnogenol) or taking 0.69 grams daily along with maritime pine bark extract and aspartic acid (Edicare, Kobayashi Pharmaceutical Co. Ltd.) modestly improves symptoms of ED (10416,50924). Another preliminary clinical trial has investigated the effects of a combination of L-arginine 2.5 grams daily for 6 months and tadalafil 5 mg daily for 3 months, both starting with the initiation of weekly extracorporeal shock wave (ESW) therapy. When compared with ESW alone, this combination modestly improves sexual function for up to 12 months (110388). The effect of L-arginine alone is not clear from these studies.
• Hypertension. Oral L-arginine can modestly reduce systolic and diastolic blood pressure. Details: Oral L-arginine seems to have additive vasodilating effects when used with angiotensin converting enzyme (ACE) inhibitors or nitrate vasodilators such as isosorbide mononitrate (7822,20192,31916). A meta-analysis of clinical research in a variety of populations shows that taking L-arginine reduces systolic and diastolic blood pressure (SBP; DPB) by an average of 6.40 mmHg and 2.64 mmHg, respectively. Sub-analyses show that these reductions occur in both normotensive and hypertensive individuals. Beneficial effects were limited to adults with a body mass index (BMI) of 18.5 to 19.9 kg/m² (110384). The effect of L-arginine on blood pressure levels in adults exposed to traffic-related air pollution (TRAP) has also been investigated. Clinical research in adults with hypertension shows that taking L-arginine 3 grams three times daily for 2 weeks modestly reduces SBP and DBP elevations following a 2-hour exposure to TRAP during an outdoor walk compared with taking placebo (110383). Doses have included 4-24 grams daily, with the best evidence of benefit for doses of less than 9 grams daily, for 2-24 weeks (7818,10636,31871,31923,32167,32201,110383,110384).
• Necrotizing enterocolitis (NEC). Oral L-arginine may help prevent NEC in premature infants. Details: In a meta-analysis of 3 clinical trials, L-arginine 260 mg/kg orally in a single dose or two divided doses daily reduces the absolute risk of NEC in premature infants by about 62% when compared with placebo. To prevent one case of NEC, 6 infants would need to be treated with L-arginine (8474,91194,96803).
• Peripheral arterial disease (PAD). Short-term use of intravenous or oral L-arginine may improve symptoms of PAD, but long-term use does not seem to be beneficial. Details: Clinical research shows that using L-arginine intravenously or orally for up to 8 weeks increases flow-mediated dilation and improves symptoms of intermittent claudication associated with PAD (3465,31857,31905). However, long-term administration of L-arginine orally for up to 6 months does not improve walking speed, walking distance, or absolute claudication distance in patients with PAD and intermittent claudication (31957,31985).
• Pre-eclampsia. Intravenous L-arginine may have beneficial effects in pre-eclampsia. However, it is unclear if oral L-arginine is effective. Details: One small clinical study shows that intravenous L-arginine 30 grams as a one-time dose decreases systolic blood pressure (SBP) by 5 mmHg and diastolic blood pressure by 11 mmHg when compared to baseline in pregnant patients with hypertension or pre-eclampsia (31847), while intravenous L-arginine 20 grams daily for 5 days decreases SBP and DBP by about 2% when compared with placebo (31978). Another small clinical study shows that oral use of L-arginine 3 grams daily for 3 weeks reduces SBP and DBP by around 7 and 5 mmHg, respectively, when compared with placebo (31938); however, taking L-arginine 12 grams daily by mouth for 5 days does not seem to improve blood pressure in these patients (11828). Another preliminary clinical trial allowing for both oral and intravenous dosing shows that taking L-arginine 3.5 grams by mouth every 6 hours or 10 grams via intravenous infusion every 8 hours shortly before or immediately after delivery and continuing until postpartum day 3 does not improve blood pressure when compared with placebo (31959). The reasons for the disparate findings are unclear, but the small study sizes, as well as variations in the dose, duration, and timing of therapy before and/or after delivery, may explain some of the differences. Oral L-arginine has also been evaluated for the prevention of pre-eclampsia. One clinical study in patients at high risk for pre-eclampsia shows that taking L-arginine 3 grams daily starting the 20th week of gestation reduces the risk of pre-eclampsia by about 74% when compared with placebo (96811). Based on these results, one case of pre-eclampsia is prevented for every 6 high-risk pregnant patients treated with L-arginine 3 grams daily. Another clinical study also shows that taking two bars of a specific medical food (Heart Bars, Nellson Nutraceutical) containing L-arginine 6.6 grams and antioxidant vitamins daily starting at 14-32 weeks gestation and continuing until delivery reduces the risk of pre-eclampsia by 44% when compared with a bar containing antioxidant vitamins alone in patients at high risk of pre-eclampsia (91197). Based on these results, one case of pre-eclampsia is prevented for every 11 high risk patients treated with this L-arginine-containing medical food.
• Pregnancy-induced hypertension. Intravenous L-arginine may have beneficial effects in pregnancy-induced hypertension. Details: Some clinical research in patients with pregnancy-induced hypertension shows that intravenous infusion of L-arginine 20 grams daily for up to 5 days decreases systolic blood pressure by 2% to 3% and diastolic blood pressure by about 3% when compared with placebo (31933,31961,31978). Clinical research in patients with pre-existing hypertension has also been conducted. One clinical trial shows that taking L-arginine 4 grams by mouth daily for 10-12 weeks does not seem to reduce blood pressure in those with pre-existing hypertension or mild gestational hypertension. However, these results are confounded by the fact that more patients taking placebo needed to be placed on antihypertensive therapy during the study. L-arginine reduced the risk of being placed on antihypertensive drug therapy during the pregnancy by 47% when compared with placebo (32191). Based on this study, for every 5 patients with pregnancy-induced hypertension treated with L-arginine over placebo, antihypertensive drug therapy is avoided in one additional patient. L-arginine has also been investigated in combination with other ingredients in patients with pre-existing hypertension. Preliminary clinical research in patients with pre-existing hypertension and a previous history of pre-eclampsia, stillbirth, intrauterine growth restriction (IUGR), or other placenta vascular disorder shows that taking L-arginine and other ingredients starting at 14 weeks gestation prevents an increase in blood pressure and reduces the percentage of patients requiring new antihypertensive medication by about 73% compared with 24.5% of those not taking this combination. In this study, L-arginine 3 grams daily was taken with magnesium 350 mg and salicylate 100 mg. Therefore, the effect of L-arginine alone is unclear. All patients in the study were taking low dose aspirin 100 mg daily (110382).

POSSIBLY INEFFECTIVE

• Chronic kidney disease (CKD). Oral or intravenous L-arginine does not seem to improve CKD. Details: Most preliminary clinical research shows that taking L-arginine, either orally for up to 6 months or intravenously short-term, does not improve kidney function, glomerular filtration rate, or renal plasma flow in patients with CKD, although proteinuria may be reduced in some patients (31844,31904,32235,32303).
• Hypercholesterolemia. Oral L-arginine does not seem to reduce cholesterol levels. Details: Preliminary clinical research in patients with hypercholesterolemia shows that taking L-arginine 21 grams daily for 4 weeks does not reduce plasma lipids (1363). Furthermore, meta-analyses of clinical research show that taking L-arginine for up to about 6 months does not reduce total or low-density lipoprotein (LDL) cholesterol levels in populations of healthy individuals or those with cardiovascular disease risk factors. However, there was a very small effect on fasting triglyceride levels (102590,102591).
• Myocardial infarction (MI). Oral L-arginine does not seem to improve outcomes after MI. Details: Patients who have had an ST-segment MI who take L-arginine within 24 hours to 21 days, titrated up to a dose of 3 grams three times a day for up to 6 months, do not seem to have reduced vascular stiffness or increased ejection fraction (13221,32137). Also, there is some concern that long-term use of L-arginine might actually worsen outcomes and increase mortality in these patients (13221). Population studies also suggest that intake of L-arginine does not reduce the risk of experiencing an acute coronary event such as MI or coronary heart disease-related mortality (3332,6896,7821,10637).
• Tuberculosis. Oral L-arginine does not seem to improve symptoms or the clearance of tuberculosis infection. Details: Clinical research shows that taking L-arginine (ArgimaxH) 6 grams daily orally for 8 weeks, with or without vitamin D, does not improve symptoms of tuberculosis or the clearance of tuberculosis infection when used with standard treatment (91196).
• Wound healing. Oral L-arginine does not seem to improve wound healing. Details: Clinical research shows that taking L-arginine (as arginine aspartate) 17 grams orally in three divided doses daily for 2 weeks does not improve epithelialization in healthy, elderly patients with catheter wounds, although it may improve collagen deposition (32247). Also, taking L-arginine (as L-arginine hydrochloride) 26 grams daily for 5 days perioperatively does not improve angiogenesis, re-epithelialization, or neutrophil count in patients undergoing skin graft donation when compared with placebo (20692). In addition, taking a wound-specific oral nutrition supplement containing L-arginine 4.5 grams, zinc, and vitamin C twice daily for 4 weeks, along with standard wound care for 8 weeks, is no more effective for wound healing than a standard oral nutrition supplement along with standard wound care (90198). L-arginine has also been studied in combination with other ingredients. Taking L-arginine enterally or orally, before or after surgery, in combination with ribonucleic acid (RNA) and either eicosapentaenoic acid (EPA) or fish oil, seems to improve wound healing when compared with a control group (5531,32174). However, due to the lack of benefit seen with the use of L-arginine alone, it is possible that this effect is due to the other ingredients or the combination of ingredients.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute respiratory distress syndrome (ARDS). Small clinical studies suggest that oral L-arginine may prevent ARDS. Details: A meta-analysis of three small studies shows that taking L-arginine 3 grams daily, starting in the second or third trimester usually until delivery, reduces the risk of ARDS in the infant by about 54% when compared to control, including placebo or no treatment (110379).
• Altitude sickness. It is unclear if oral L-arginine is beneficial in patients with altitude sickness. Details: Preliminary clinical research shows that taking L-arginine 4 grams orally three times daily for 2 days while ascending to a high altitude and for 24 hours while at high altitude does not reduce altitude sickness when compared with placebo (31955).
• Anthracycline cardiotoxicity. Although there is interest in using oral L-arginine for anthracycline cardiotoxicity, there is insufficient reliable information about the clinical effects of L-arginine for this purpose.
• Anemia of chronic disease. It is unclear if oral L-arginine is beneficial for anemia in patients with chronic kidney disease. Details: One very small clinical study in elderly adults with chronic kidney disease and anemia shows that taking L-arginine orally 1.3 grams daily might increase hemoglobin and erythropoietin levels in some patients when compared to baseline (31988). The validity of these findings is limited by the small study size and the lack of a comparator group.
• Asthma. It is unclear if oral L-arginine is beneficial in patients with asthma. Details: Preliminary clinical research in adults with severe asthma shows that taking L-arginine 0.05 gram/kg ideal body weight twice daily does not reduce asthma exacerbations when compared with placebo (104223). This study may have been inadequately powered to detect a difference in exacerbation rates between groups. While other studies have shown adverse airway effects in patients with asthma (121,31849), this study demonstrated no change in exacerbations and reported no adverse airway effects.
• Athletic performance. Small clinical studies suggest that oral L-arginine may improve measures of athletic performance. Details: A meta-analysis of 5 small clinical trials shows that taking L-arginine seems to modestly improve measures of cardiorespiratory fitness, as measured by a 0.07 L/minute increase in maximal oxygen uptake, when compared with control (105064). L-arginine has also been examined for its effects on athletic performance. Most research suggests that taking L-arginine does not improve athletic performance. However, clinical trials are small and may not be adequately powered to detect a difference in these outcomes Taking L-arginine as a single dose of 5 or 6 grams or as 5-10 grams daily for 2-4 weeks does not improve grip strength, strength during resistance exercise, power output during cycling, or muscle function during recovery from intense resistance exercise in healthy adults (91190,97393,99265,110381,110389). Also, taking L-arginine 5 grams daily for 4 weeks (Bioarginina Farmaceutici Damor) or 8 grams daily for 8 days does not increase swim speed (110381,110386). In contrast, some research suggests that drinking a single beverage containing the same dose of L-arginine 6 grams increases the time to exhaustion during high-intensity exercise when compared with placebo (32180). Also, a meta-analysis of small clinical trials shows that supplementation with L-arginine has a large beneficial effect on aerobic performance and a small beneficial effect on anaerobic performance. However, publication bias was evident in the aerobic performance data, limiting these conclusions. Doses found to be beneficial in this analysis included an acute dose of L-arginine 0.15 gram/kg 60-90 minutes before performance or chronic dosing of 1.5 grams to 2 grams daily for 4-7 weeks for aerobic performance. The chronic dose of L-arginine most likely to be beneficial for anaerobic performance is unclear from this analysis due to inclusion of studies using arginine alpha-ketoglutarate (110395). With the exception of a few studies which include a very small number of healthy females (99265,110395,110386), research on the use of L-arginine for athletic performance has focused almost exclusively on healthy males. Also, studies are heterogeneous with respect to sport and endpoints. Therefore, whether results can be applied to females or specific athletes is unclear. L-arginine has also been evaluated in overweight males. One small clinical study shows that taking a single dose of L-arginine 6 grams 90 minutes prior to high-intensity interval training seems to improve exercise tolerance by improving ventilation, heart rate, and oxygen uptake when compared with placebo (105060). L-arginine has also been evaluated in combination with other ingredients. Research in male soccer players shows that taking L-arginine 1.2 grams and L-citrulline 1.2 grams daily for 7 days increases total power output over a 10-minute cycling test and improves subjective perceptions of exertion when compared with placebo (100956). Another study shows that taking L-arginine 1.5 or 3 grams daily, in combination with grape seed extract, increases physical working capacity at fatigue threshold when compared with pretreatment in untrained, college-aged males (32164).
• Beta-thalassemia. It is unclear if oral L-arginine is beneficial in children with beta-thalassemia. Details:Preliminary clinical research in children aged 6-18 years treated conventionally for pulmonary hypertension related to beta-thalassemia shows that taking L-arginine 0.1 mg/kg daily for 60 days reduces Doppler echocardiography pulmonary arterial pressure by 35% compared with baseline. This measurement was increased by up to 15% in children given conventional treatments only; however, a statistical comparison between these treatment groups was lacking (110391).
• Breast cancer. It is unclear if oral L-arginine is beneficial in patients with breast cancer. Details: Preliminary clinical research shows that taking L-arginine 30 grams daily for 3 days prior to chemotherapy does not improve the clinical response rate in breast cancer patients when compared with placebo (32282).
• Cognitive impairment. It is unclear if oral L-arginine is beneficial in patients with cognitive impairment. Details: A small clinical trial in frail adults aged 65 years of age and up with hypertension shows that taking L-arginine (Bioarginina) 1.66 grams twice daily for 4 weeks modestly improves cognitive function when compared to placebo (110385).
• Congestive heart failure (CHF). It is unclear if oral L-arginine is beneficial in patients with CHF. Details: One small clinical study in patients with CHF stage 2-3 shows that taking L-arginine 15 grams daily for 5 days, in combination with conventional treatment, seems to improve glomerular filtration rate (GFR), creatinine clearance, and sodium and water elimination after saline loading, indicating an improvement in kidney function (3596).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral L-arginine is beneficial in patients with severe COVID-19 infection. Details: A small clinical trial in patients with severe COVID-19 shows that receiving oral L-arginine (Argin, Nutrigrow, India) 3 grams daily for a maximum of 10 days while on oxygen support does not affect the percentage of patients weaned off oxygen support after 10 days, the length of time requiring oxygen support, the duration of hospitalization, or the incidence of adverse thrombotic events, compared with placebo (110392). This study may not have been adequately powered to detect differences between groups. An interim analysis of a small clinical trial in patients hospitalized with severe COVID-19 shows that adding oral L-arginine (Bioarginina, Farmaceutici Damor) 1.66 grams twice daily to standard therapy throughout hospitalization increases the rate of respiratory support reduction by 60% after 10 days of therapy, but not after 20 days of therapy, when compared with placebo. L-arginine also significantly reduced the length of hospital stay. The median hospital stay was 25 days and 46 days, respectively, for L-arginine and placebo (106500). L-arginine has also been investigated in combination with other ingredients for post-acute COVID symptoms. Preliminary clinical research in adults with persistent fatigue following a COVID infection shows that taking L-arginine 1.66 grams plus vitamin C 500 mg (Bioarginina C, Farmaceutici Damor) twice daily for 28 days increases the distance walked in 6 minutes by 30 meters and reduces the percentage of patients with fatigue by about 89%, when compared with placebo. Grip strength was also increased (110390).
• Coronary artery bypass graft (CABG) surgery. It is unclear if oral L-arginine is beneficial for preventing complications after CABG surgery. Details: Preliminary clinical research shows that venous infusion of L-arginine hydrochloride 30 grams as a 10% solution over 15 minutes helps maintain mean arterial pressure, coronary vascular resistance, and graft blood flow when compared with a placebo infusion in patients that have undergone CABG (31840). Administering L-arginine 7.5 grams in 500 mL of cardioplegic solution also seems to reduce wedge pressure and intensive care unit stay in patients undergoing CABG; however, it does not reduce hospital stay duration or postoperative complications when compared with cardioplegic solution alone (31958,31886).
• Critical illness (trauma). Oral L-arginine has only been evaluated in combination with other ingredients; its effects when used alone are unclear. Details: A meta-analysis of clinical research shows that taking L-arginine orally with glutamine, nucleotides, and omega-3 fatty acids reduces the recovery time, the need for ventilation, and infection rates in critically ill patients, but does not reduce the risk of mortality (31853).
• Cyclosporine-induced nephrotoxicity. Although there is interest in using oral L-arginine for cyclosporine-induced nephrotoxicity, there is insufficient reliable information about the clinical effects of L-arginine for this purpose.
• Cystic fibrosis. It is unclear if oral L-arginine is beneficial in patients with cystic fibrosis. Details: Preliminary clinical research in teens and adults with cystic fibrosis shows that twice daily inhalation with L-arginine 500 mg for 2 weeks does not improve lung function when compared with inhaling 2.6% hypertonic saline twice daily (96807).
• Dental caries. Small clinical studies suggest that using a dentifrice containing L-arginine might prevent dental caries. Details: A meta-analysis of small studies shows that use of a dentifrice containing L-arginine 1.5% w/w in combination with calcium base (Dical or calcium carbonate) and fluoride 1450 ppm 2-3 times daily for up to 2 years reduces the risk of developing dental caries by a small to moderate amount when compared with a dentifrice containing only fluoride in children and adults (96806). Also, preliminary clinical research shows that using a confection containing an L-arginine complex (CaviStat) for one year reduces the number of dental caries in molars of children when compared with a sugarless mint control (32011).
• Dental hypersensitivity. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that using a toothpaste containing L-arginine, calcium, and fluoride twice daily reduces dentin hypersensitivity when compared with pretreatment or control (32130,32131,32132,32177).
• Diabetes. Small, low-quality studies suggest that oral L-arginine does not improve glycemic control in people with type 2 diabetes. Details: A meta-analysis of small, low-quality studies shows that taking L-arginine 2-20 grams daily for up to 77 weeks decreases fasting blood glucose and serum insulin levels in adults without diabetes. However, no improvements occurred in adults WITH type 2 diabetes. This may be explained by previous studies which suggest L-arginine affects glucose control only in the early steps of beta-cell dysfunction. L-arginine did not improve insulin resistance or glycated hemoglobin (HbA1c) in patients with or without diabetes (104225). Also, a prospective observational study in patients with type 1 or type 2 diabetes has found that taking a specific product (Flebotrofine, AMNOL Chimica Biologica) containing L-arginine for 3 months is not associated with improvements in HbA1c, cholesterol, or triglyceride levels when compared with baseline. Other ingredients in this product included diosmin, troxerutin, hesperidin, black currant extract, and gotu kola extract (108151). The validity of these findings is limited by the lack of a comparator group.
• Diabetic foot ulcers. It is unclear if oral or subcutaneous L-arginine is beneficial in patients with diabetic foot ulcers. Details: A very small clinical study shows that administering L-arginine subcutaneously at the site of diabetic foot ulcers does not decrease healing time or rate of amputation when combined with conventional therapies (14914). Also, taking a specific drink containing L-arginine 7 grams, L-glutamine 7 grams, and calcium hydroxymethylbutyrate (HMB) 1.5 grams (Juven/Abound, Abbott Nutrition) orally twice daily for 16 weeks does not improve diabetic foot ulcer healing when compared with a control drink in non-ischemic patients or those with normal albumin levels. However, in specific populations with low albumin and/or poor limb perfusion, up to 74% more patients had total wound healing when compared with the control drink (96637).
• Diabetic neuropathy. It is unclear if oral L-arginine is beneficial in patients with diabetic neuropathy. Details: Preliminary clinical research shows that taking L-arginine 3 grams daily for 3 months does not improve circulation, disability, or nerve function in patients with diabetic neuropathy when compared with placebo (32145).
• Head and neck cancer. It is unclear if oral L-arginine is beneficial in patients with head and neck cancer. Details: Small clinical studies suggest that enteral nutrition supplemented with L-arginine does not seem to have any beneficial effects on markers of immune function such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), length of postoperative hospital stay, or fistula rates; however, it seems to reduce wounds and general infections after surgery in patients with head and neck cancer when compared with control (10160,32008).
• Heart failure. It is unclear if oral L-arginine is beneficial in patients with heart failure. Details: Preliminary clinical research in adults with heart failure shows that taking L-arginine 3.0-12.6 grams orally daily for 6-12 weeks does not consistently improve exercise tolerance or peripheral vascular resistance (3595,6028,32138). However, some research shows that taking L-arginine 1000 mg three times daily for 10 weeks modestly improves measures of cardiac function compared with placebo (110380). Although some research disagrees (32138), most research shows that taking L-arginine modestly improves quality of life (3595,110380).
• Heart transplant complications. It is unclear if oral L-arginine is beneficial in patients that have received a heart transplant. Details: Preliminary clinical research shows that taking L-arginine 6 grams orally twice daily for 6 weeks increases walking distance and oxygen uptake and delays the ventilatory threshold in heart transplant patients when compared with baseline (32150).
• HIV/AIDS-related wasting. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients with HIV/AIDS shows that taking L-arginine orally, in combination with hydroxymethylbutyrate (HMB) and glutamine for 8 weeks, increases body weight, particularly lean body mass, and positively affects immune status when compared with placebo (1909). However, other clinical research in HIV-positive patients shows that taking L-arginine 7.4 grams daily orally, in combination with omega-3 fatty acids and a balanced oral nutritional supplement for 6 months, does not improve body weight or fat mass, total energy intake, or immune status when compared to taking the nutritional supplement alone (113).
• Impaired glucose tolerance (prediabetes). It is unclear if oral L-arginine can prevent the development of type 2 diabetes in adults with prediabetes. Details: Clinical research shows that taking L-arginine (Bioarginine, Farmaceutici Damor) 3.2 grams orally twice daily for 18 months does not reduce the incidence of diabetes in patients with impaired glucose tolerance (prediabetes). However, when assessed one year after treatment discontinuation, patients who took L-arginine had a 58% lower risk of developing diabetes when compared with placebo (91195).
• Infertility. It is unclear if oral L-arginine improves outcomes in people undergoing an assisted reproductive technology (ART) program. Details: Some preliminary clinical research shows that taking L-arginine 16 grams daily decreases the cancellation rate of in vitro fertilization (IVF) and increases the number of oocytes collected in females undergoing an ART program when compared with control. However, taking L-arginine does not seem to improve the number of viable pregnancies (31842). A small clinical study of females undergoing an ART program shows that taking a combination product containing L-arginine 1 gram with folate 200 mcg or L-arginine 2 grams, folate 400 mcg, and vitamin E 10 mg daily for 12 weeks does not affect the hCG-positive rate or clinical pregnancy rate when compared with placebo. A subgroup analysis suggests that taking these combination products might improve HCG-positive and clinical pregnancy rates in females who are undergoing ART due to male infertility (104224). However, this small study was not adequately powered to detect a difference in these outcomes, limiting the validity of these findings.
• Interstitial cystitis. Small clinical studies suggest that oral L-arginine may improve pain in interstitial cystitis. Details: Taking L-arginine orally seems to reduce some symptoms, especially pain, that are associated with interstitial cystitis (107,114,3460,31855,32267). Research shows that patients with interstitial cystitis having a bladder capacity greater than 800 mL and/or a history of recurrent genitourinary infections might respond more favorably to L-arginine than patients with bladder capacity less than 800 mL and/or no history of recurrent genitourinary infections. Three months of treatment may be necessary before significant symptom improvement occurs (3460). However, L-arginine does not seem to reduce the need to urinate at night or improve urgency or frequency of urination (3460,31855).
• Intrauterine growth restriction (IUGR). Small clinical studies suggest that oral or intravenous L-arginine may increase birthweight in IUGR. Details: A meta-analysis of mainly small studies shows that L-arginine given orally or intravenously in the third trimester for a time period of 7 days or until delivery increases the birthweight by up to 650 grams in patients with an IUGR pregnancy. Furthermore, there is evidence from a small number of these studies that L-arginine supplementation decreases the risk of neonatal respiratory distress syndrome and fetal intracranial hemorrhage (96804). A more recent meta-analysis of small studies also shows that taking L-arginine 3 grams daily, starting in the second or third trimester usually until delivery, reduces the risk of an IUGR infant by about 32% when compared to control, including placebo or no treatment (110379). Doses used in clinical research have usually been 3 grams daily orally, although some studies have used up to 20 grams intravenously (31930,31937,96804,110379). However, supplementation with L-arginine does not seem to increase birthweight or reduce neonatal mortality or morbidity when compared with placebo in patients with severe IUGR (32083).
• Kidney transplant. Small clinical studies suggest that oral L-arginine may not improve kidney function in patients after kidney transplantation. Details: Although preliminary clinical research showed some benefit, evidence from other clinical research shows that infusion with L-arginine does not increase renal plasma flow or glomerular filtration rate in kidney transplant patients treated with cyclosporine, including those experiencing transplant dysfunction (112,31876,32229). Other evidence suggests that intravenous L-arginine improves kidney function only in transplant patients receiving organs with a short cold ischemia time or those receiving kidneys from young donors (31887).
• Male infertility. It is unclear if oral L-arginine is beneficial in males with infertility. Details: Preliminary clinical research shows that taking L-arginine 4 grams daily for 12 weeks does not improve semen quality in males with oligospermia when compared with placebo (32209). However, one small clinical study shows that a specific formulation of L-arginine aspartate and maritime pine bark extract (Prelox), taken for 6 months, improves sperm quality in males with idiopathic male infertility when compared to baseline (32061). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to L-arginine, maritime pine bark, or the combination.
• Mitochondrial myopathies. Small clinical studies suggest that intravenous L-arginine may modestly improve symptoms in patients with MELAS (myoclonic epilepsy with lactic acidosis and stroke-like episodes syndrome). Details: Preliminary clinical research shows that infusions of L-arginine, 0.5 grams/kg administered within one hour of stroke-like symptoms, improves headaches, nausea, vomiting, transient blindness, and the appearance of bright spots when compared to pretreatment in patients with MELAS (31943,99263). Also, taking oral L-arginine 4-24 grams daily for 18 months seems to reduce the frequency and severity of stroke-like symptoms associated with MELAS when compared to baseline (31943). However, other preliminary clinical research shows that taking oral L-arginine 0.3-0.5 grams/kg daily in three divided doses for 2 years does not reduce the severity of MELAS symptoms, including migraine and stroke-like episodes. If a stroke-like episode did occur, administration of intravenous L-arginine 0.5 grams/kg improved headache, nausea, vomiting, and visual disturbance (99263). The validity of this research is limited by the small study sizes and the absence of comparator groups.
• Migraine headache. Although there is interest in using oral L-arginine for migraine, there is insufficient reliable information about the clinical effects of L-arginine for this condition.
• Muscular dystrophy. There is limited evidence on the oral use of L-arginine in patients with Duchenne muscular dystrophy. Details: A very small study in five children with Duchenne muscular dystrophy, shows that drinking a beverage containing L-arginine hydrochloride (L-Arginine Hydrochloride, Selectchemie) 2.5 grams three times daily, in addition to metformin 250 mg twice daily, for 16 weeks improves motor function by 4% and increases distance walked in two minutes by 9.6 meters when compared to baseline (96805). The validity of these findings is limited by the very small study size and lack of a comparator group.
• Nitrate tolerance. It is unclear if oral L-arginine is beneficial for nitrate tolerance. Details: A very small crossover study in adults with stable angina shows that taking L-arginine orally 700 mg four times daily for up to 10 days seems to prevent tolerance to transdermal nitrate when compared with placebo (8475).
• Obesity. Small clinical studies suggest that oral L-arginine may be beneficial for weight loss. Details: A meta-analysis of mainly small clinical trials shows that taking L-arginine daily for at least 8 weeks modestly reduces body weight, body mass index (BMI), and waist circumference when compared with placebo. However, when taking L-arginine for less than 8 weeks, BMI and body weight were not affected. The optimal dose of L-arginine was 2-6 grams (110398). An additional small clinical study suggests that taking a specific arginine supplement (NOW Foods) 3 grams by mouth three times daily for 12 weeks, in addition to receiving dietary counseling, reduces waist circumference by 4-6 cm and reduces body weight by 1.8-2.9 kg when compared to baseline in obese females 18-40 years of age (91193). The validity of these findings is limited by the lack of a comparator group.
• Oral mucositis. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study shows that taking a specific combination of L-arginine 7 grams, L-glutamine 7 grams, and hydroxymethylbutyrate (HMB) 1.2 grams (Abound; Abbott) in water twice daily during chemoradiotherapy treatment for head and neck cancer does not reduce the incidence of severe oral mucositis when compared with a historical control (99243). The validity of this finding is limited by the lack of a placebo control.
• Periodontitis. It is unclear if oral L-arginine is beneficial in patients with periodontitis. Details: Preliminary clinical research in patients with chronic periodontitis shows that using L-arginine aspartate (Yuria-Pharm, Ukraine) 1 gram three times daily orally for 10 days after scaling and root planing, modestly reduces bleeding on probing but not periodontal pocket depth, when compared with untreated controls (108926).
• Physical performance. It is unclear if oral L-arginine is beneficial for improving physical performance in older adults. Details: A small study in physically active females 65 years of age and older shows that taking L-arginine 8 grams as a single dose does not improve lower body strength, measured by knee flexion and extension tests, or functional performance, measured by sit-stand, tandem gait, and timed up-and-go tests, when compared with placebo (96812).
• Polycystic ovary syndrome (PCOS). Oral L-arginine 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 N-acetylcysteine 1200 mg daily plus L-arginine 1600 mg daily for 6 months modestly improves menstrual function and decreases insulin resistance in patients with PCOS when compared to baseline (32094). The validity of these findings is limited by the lack of a comparator group.
• Postoperative infection. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Small clinical studies show that taking L-arginine, enterally or orally, either before or after surgery, in combination with fish oil, or with ribonucleic acid (RNA) and eicosapentaenoic acid (EPA), seems to reduce the rate of perioperative infection when compared with a control group. The risk of infection was 41% lower when compared to taking no arginine-based formulations. However, there is no good evidence to support the use of L-arginine alone for this purpose, and it is possible that this effect is due to the other ingredients or the combination of ingredients (5531,32174,32196).
• Postoperative recovery. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Small clinical studies show that taking L-arginine, enterally or orally, either before or after surgery, in combination with fish oil, or with ribonucleic acid (RNA) and eicosapentaenoic acid (EPA), seems to reduce the recovery time after surgery or serious illness when compared with a control group. This seems to be related to a reduced number of perioperative infections and improved wound healing. However, there is no good evidence to support the use of L-arginine alone for this purpose, and it is possible that this effect is due to the other ingredients or the combination of ingredients (5531,32174,32196). The effect of another combination product containing L-arginine is unclear. In one clinical study, taking a combination product (Abound, Abbott) containing L-arginine 7 grams, glutamine 7 grams, and hydroxymethylbutyrate 1.2 grams orally daily for 3 days before and 7 days after abdominal surgery did not reduce the incidence of wound infection or other complications when compared with placebo (99413). However, when a similar combination of L-arginine 14 grams, glutamine 14 grams, and hydroxymethylbutyrate 3 grams (Heallagen) was taken orally daily for one month before heart surgery, the length of hospital and ICU stay were reduced by about one day. Recovery, based on some but not all biochemical or other measurements, was also improved. However, there was no difference in risk of overall postoperative complications (110394). The discrepancies between these two studies may be related to differences in the dose or duration of the combination product and/or the type of surgery.
• Pressure ulcers. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Oral L-arginine has been evaluated in combination with other ingredients for the treatment of grade II-IV pressure ulcers. Two small clinical studies in hospitalized patients show that administering an oral nutritional supplement enriched with L-arginine, zinc, and vitamin C improves ulcer healing when compared with a standard diet (31953,87173). A small preliminary clinical study in sedentary older adults in care facilities shows that giving an oral or enteral combination of L-arginine 7.4 grams, L-glutamine 7.4 grams, and hydroxymethylbutyrate (HMB) 1.3 grams (Abound, Abbott) daily for 20 weeks reduces median time to healing by 48 days when compared with standard care only (110396). Also, preliminary clinical research in patients living in long-term care facilities with grade II-IV pressure ulcers shows that taking an oral nutritional supplement enriched in protein, energy, L-arginine, vitamin C, and zinc daily for 9 weeks reduces ulcer area and decreases oozing when compared to baseline (32045). The validity of this finding is limited by the lack of a comparator group.
• Preterm labor. Small clinical studies suggest that oral L-arginine may prevent preterm labor. Details: A meta-analysis of three small studies shows that taking L-arginine 3-6.6 grams daily, starting in the second or third trimester usually until delivery, reduces the risk of preterm labor by about 50% when compared to control, usually placebo (110379).
• Pulmonary hypertension. It is unclear if oral L-arginine is beneficial in children with pulmonary hypertension related to beta-thalassemia. Details: Preliminary clinical research in children aged 6-18 years treated conventionally for pulmonary hypertension related to beta-thalassemia shows that taking L-arginine 0.1 mg/kg daily for 60 days reduces Doppler echocardiography pulmonary arterial pressure by 35% compared with baseline. This measurement was increased by up to 15% in children given conventional treatments only; however, a statistical comparison between these treatment groups was lacking (110391).
• Radiation dermatitis. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with head and neck cancer shows that taking a combination of L-arginine 7 grams, L-glutamine 7 grams, and hydroxymethylbutyrate (HMB) 1.2 grams (Abound, Abbott) in water twice daily from the first day of radiation to approximately 1 week after completion does not reduce the number of patients with severe dermatitis when compared with taking no supplement. However, there was a 34% reduction in the incidence of moderate dermatitis and the overall duration of dermatitis was reduced (96639).
• Restenosis. It is unclear if intravenous L-arginine helps to prevent restenosis after stent implantation. Details: Some clinical research suggests that intravenous and intracoronary infusion of L-arginine during stent implantation followed by oral L-arginine for 2 weeks does not reduce the risk of restenosis when compared with placebo (31925). However, local delivery of 6 mL of L-arginine 100 mg/mL for 15 minutes after stent deployment seems to reduce neointimal formation at 6 months after stent placement when compared with placebo (31883).
• Respiratory tract infections. Although there is interest in using oral L-arginine for respiratory tract infections, there is insufficient reliable information about the clinical effects of L-arginine for these conditions.
• Schizophrenia. It is unclear if oral L-arginine is beneficial in patients with schizophrenia. Details: A small clinical study shows that taking L-arginine 3 grams twice daily for 3 weeks, in conjunction with an individualized medication regimen, does not improve positive, negative, or depressive symptoms associated with schizophrenia when compared with taking the medication regimen alone (99264).
• Sexual dysfunction. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in females with sexual dysfunction who are taking oral contraceptives shows that taking a specific combination product (Lady Prelox, Horphag Research) containing L-arginine, maritime pine bark extract, L-citrulline, and rose hip extract daily for 8 weeks improves symptoms of sexual dysfunction by 18% when compared with a control group (91963). Taking the same product in a dose of 2 tablets twice daily for 8 weeks, in addition to the lifestyle management program, improves vaginal dryness in pre- and post-menopausal patients when compared with lifestyle management alone (103611). It is unclear if this effect is due to L-arginine, the other ingredients, or the combination.
• Sickle cell disease. Small clinical studies suggest that oral or intravenous L-arginine may modestly improve complications in patients with sickle cell disease. Details: Two small clinical studies in hospitalized children aged 3-19 years with sickle cell disease-related veno-occlusive crisis shows that administering L-arginine intravenously or orally 100 mg/kg three times daily for 5 days or until discharge reduces total opioid use by 26% to 54%, pain scores at discharge by 23%, and median length of hospital stay by about 36 hours when compared with placebo (97392,105063). Another very small clinical study in patients aged 13-63 years with sickle cell disease shows that taking L-arginine 0.1 grams/kg orally three times daily for 5 days reduces pulmonary hypertension when compared to baseline (11428).
• Stress. Oral L-arginine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking a single dose of L-arginine 50 mg plus L-theanine 200 mg modestly reduces stress associated with a stress-loading test when compared with placebo, but was no more effective than taking L-theanine alone (110393).
• Valproic acid-induced toxicities. Although there is interest in using intravenous L-arginine for valproic acid toxicity, there is insufficient reliable information about the clinical effects of L-arginine for this purpose. More evidence is needed to rate L-arginine for these uses.

(Read more about L-ARGININE)

EFFECTIVE

• Pantothenic acid deficiency. Taking pantothenic acid 5-10 mg daily is effective for treating and preventing pantothenic acid deficiency (15).

POSSIBLY INEFFECTIVE

• Radiation dermatitis. Topical dexpanthenol does not seem to be beneficial for preventing or treating radiation dermatitis. Details: Applying dexpanthenol, an analog of pantothenic acid, twice daily to areas of irradiated skin does not seem to reduce erythema, desquamation, itching, or pain following radiation treatment (7192). Also, applying dexpanthenol 0.5% cream (Bepanthen, Hoffmann LaRoche ) daily during radiation therapy and for 2 weeks after completing radiation therapy is less effective than methylprednisolone aceponate 0.1% cream (Advantan) at reducing radiation-induced skin irritation (67779).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral or topical pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In adults with mild to moderate acne, clinical research shows that taking a specific supplement (Pantothen, Avilan Marketing LLC) providing pantothenic acid 1.1 grams twice daily in addition to other B vitamins for 12 weeks modestly reduces total and non-inflammatory lesion counts when compared with placebo (105188). Also, in adolescents or young adults with mild to moderate acne, preliminary clinical research shows that topical application with a gel containing D-panthenol 4%, hydrogen peroxide 4%, and salicylic acid 0.5% once daily for 60 days modestly reduces acne lesions when compared with baseline (105189). The validity of this finding is limited by the lack of a comparator group.
• Alcoholism. Although there is interest in using oral pantothenic acid for improving recovery from alcoholism, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Allergic rhinitis (hay fever). Although there is interest in using oral pantothenic acid for allergic rhinitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Alopecia areata. Pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults with diffuse hair loss shows that intramuscular administration of dexpanthenol 250 mg and biotin 5 mg once weekly for 6 weeks reduces hair fall count at weeks 1 and 8, but only increases hair density at week 1, when compared to baseline (111366). The validity of these findings is limited by the study's small size, short duration, and lack of comparator group.
• Anxiety. Although there is interest in using oral pantothenic acid for anxiety, there is insufficient reliable information about the clinical effects of pantothenic acid for this purpose.
• Asthma. Although there is interest in using oral pantothenic acid for asthma, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Athletic performance. Although there is interest in using oral pantothenic acid to improve athletic performance, there is insufficient reliable information about the clinical effects of pantothenic acid for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Oral pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some small outdated clinical studies in children diagnosed with hyperkinesis suggest that taking calcium pantothenate 1.2 grams, alone or in combination with niacinamide, ascorbic acid, and pyridoxine, does not improve symptoms of hyperactivity when compared with placebo (3351,9957). It is unclear what effects pantothenic may have, if any, in children with a modern diagnosis of ADHD.
• Atopic dermatitis (eczema). It is unclear if topical pantothenic acid is beneficial in infants or children with atopic dermatitis. Details: One preliminary clinical trial in infants and children with stable mild atopic dermatitis shows that topical application of an emollient containing panthenol (Bepanthen, SensiDaily, Bayer Consumer Care AG) for 3 months is as effective as a reference emollient for reducing symptoms and preventing a flare. However, the efficacy of the reference emollient (Stelatopia Emollient Cream, Mustela; Laboratoires Expanscience) is unclear based on available preliminary clinical research (105190).
• Autism spectrum disorder. Although there is interest in using oral pantothenic acid for autism spectrum disorder, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Carpal tunnel syndrome. Although there is interest in using oral pantothenic acid for carpal tunnel syndrome, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral pantothenic acid for CFS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Conjunctivitis. Although there is interest in using oral or ocular pantothenic acid for conjunctivitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Constipation. It is unclear if oral or intramuscular dexpanthenol is beneficial for constipation. Details: Preliminary clinical research shows that administering dexpanthenol (Bepanthene), an analog of pantothenic acid, 400 mg orally or 500 mg intramuscularly daily for 5 days decreases the time to a bowel movement in patients with chronic or occasional constipation when compared with an oral placebo (67822).
• Dandruff. Although there is interest in using oral or topical pantothenic acid for dandruff, is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Depression. Although there is interest in using oral pantothenic acid for depression, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Diaper rash. Although there is interest in using topical pantothenic acid for diaper rash, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Dry eye. Although there is interest in using ocular pantothenic acid for dry eye, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Dry skin. It is unclear if topical dexpanthenol is beneficial for patients with dry skin. Details: A small, open-label study in healthy adults with dry skin shows that cleansing the skin with a dexpanthenol-containing liquid cleanser (DCLC, Bepanthen SensiControl Daily Gentle Body Wash) daily for 4 weeks increases stratum corneum hydration by 17% without affecting skin barrier function, pH, or microbiome when compared to baseline (111262). The validity of these findings is limited by the lack of blinding and a comparator group.
• Epilepsy. Although there is interest in using oral pantothenic acid for epilepsy, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Eye trauma. It is unclear if ocular dexpanthenol is beneficial for eye trauma. Details: Some preliminary clinical research shows that using eyedrops containing dexpanthenol 5%, a derivative of pantothenic acid, two drops four times daily for 28 days following surgery for retinal detachment reduces eye pain and discomfort when compared with placebo drops (67783). However, using a specific dexpanthenol 5% ointment (Bepanthen) does not seem to improve corneal epithelial wound healing following phototherapeutic keratectomy when compared with placebo (67801).
• Heart failure. Although there is interest in using oral pantothenic acid for heart failure, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Herpes zoster (shingles). Although there is interest in using oral or topical pantothenic acid for shingles, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Insomnia. Although there is interest in using oral pantothenic acid for insomnia, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Laser skin resurfacing. It is unclear if topical dexpanthenol or pantothenic acid can reduce adverse effects after laser skin resurfacing procedures. Details: A preliminary clinical study shows that use of a dexpanthenol-containing ointment (Bepanthen Wound Healing Ointment, Bayer) once daily modestly reduces the diameter of lesions up to 3 days after fractional carbon dioxide laser resurfacing when compared with petroleum jelly (105743). Also, applying a specific cream (Cicaplast Baume B5 cream, L'Oreal) containing panthenol 5%, madecassoside, copper, zinc, and manganese to one side of the face for 28 days reduces decrustation time by approximately one day when compared with a control emollient. Redness and swelling were lower at 3 days, but there was no difference in pain and burning (105742). It is unclear if these effects are due to pantothenic acid, other ingredients, or the combination.
• Multiple sclerosis (MS). Although there is interest in using oral pantothenic acid for MS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Muscular dystrophy. Although there is interest in using oral pantothenic acid for muscular dystrophy, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Nipple fissures. Although there is interest in using topical pantothenic acid for nipple fissures, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Obesity. Although there is interest in using oral pantothenic acid for obesity, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Pain (chronic). It is unclear if oral or topical pantothenic acid is beneficial for the management of various forms of chronic pain. Details: Although there is interest in using oral or topical pantothenic acid for various forms of chronic pain, including neuropathy and arthritis, there is limited information available about the clinical effects of pantothenic acid for this purpose. One review of preliminary clinical research found that calcium pantothenate does not reduce symptoms of arthritis in patients with rheumatoid arthritis or osteoarthritis (10433).
• Parkinson disease. Although there is interest in using oral pantothenic acid for Parkinson disease, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Poison oak and poison ivy dermatitis. Although there is interest in using topical pantothenic acid for poison ivy dermatitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Postoperative pain. It is unclear if oral pantothenic acid is beneficial for postoperative pain. Details: In post-tonsillectomy patients aged 5-12 years, preliminary clinical research shows that taking pastilles containing dexpanthenol (Bepanthene, Bayer) 100 mg three times daily reduces pain when compared with placebo. Postoperative pain was modestly reduced at 1, 3, 7, and 14 days after surgery (105191).
• Postoperative sore throat. It is unclear if pantothenic acid lozenges are beneficial for postoperative sore throat. Details: Preliminary clinical research shows that taking two lozenges containing dexpanthenol, an analog of pantothenic acid, 200 mg 30 minutes prior to general anesthesia reduces the incidence and severity of postoperative sore throat when compared with a benzydamine hydrochloride or placebo spray (67792).
• Pregnancy-related leg cramps. Although there is interest in using oral pantothenic acid for pregnancy-related leg cramps, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Premenstrual syndrome (PMS). Although there is interest in using oral pantothenic acid for PMS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Respiratory tract infections. Although there is interest in using oral pantothenic acid for respiratory tract infections, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Rhinosinusitis. It is unclear if nasal dexpanthenol is beneficial for rhinosinusitis. Details: Preliminary clinical research shows that using a nasal spray (MarPlus) containing dexpanthenol, an analog of pantothenic acid, on the first, second, fourth, and sixth week after endoscopic sinus surgery reduces nasal discharge, but not other symptoms associated with chronic rhinosinusitis, when compared with saline nasal spray (67808).
• Skin irritation. It is unclear if topical dexpanthenol is beneficial for preventing or treating skin irritation due to sodium lauryl sulfate. Details: Preliminary clinical research shows that applying dexpanthenol (Bepanthol Handbalsam), an analog of pantothenic acid, twice daily for 26 days does not prevent sodium lauryl sulfate-induced skin irritation (67785). However, dexpanthenol may be effective for treating skin irritation caused by sodium lauryl sulfate. Use of an ointment containing dexpanthenol 1% to 5% twice daily for up to 30 days following skin exposure to sodium lauryl sulfate seems to reduce skin water loss, skin roughness, and skin inflammation when compared to control (67802,67806).
• Ulcerative colitis. Although there is interest in using oral or rectal pantothenic acid for ulcerative colitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Vertigo. Although there is interest in using oral pantothenic acid for vertigo, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Wound healing. Preliminary clinical research suggests that oral dexpanthenol might be beneficial for wound healing. Details: In post-tonsillectomy patients aged 5-12 years, preliminary clinical research shows that taking pastilles containing dexpanthenol (Bepanthene, Bayer) 100 mg three times daily improves wound healing when compared with placebo. Depending on the type of surgery, wound healing occurred in 2.3-2.9 times as many patients within 7 days of surgery, and in 13% to 35% more patients within 14 days, when compared with placebo (105191). More evidence is needed to rate pantothenic acid for these uses.

(Read more about PANTOTHENIC ACID)

POSSIBLY EFFECTIVE

• Ulcerative colitis. Clinical research suggests that taking slow-release, phosphatidylcholine-rich phospholipids (Sterpur P-30 Granulat, Stern-Lecithin and Soja GmbH) improves symptoms and remission rate in patients with ulcerative colitis (68839,93389,93390,105728). A pooled analysis of 3 small randomized clinical trials in adults with chronic, active, ulcerative colitis at a single site shows that taking this specific form of phosphatidylcholine 1-4 grams daily for 3 months increases the odds of achieving clinical remission by 9.7 times when compared with placebo. Overall, 49% of the patients taking phosphatidylcholine achieved clinical remission. Taking phosphatidylcholine also improved quality of life and clinical improvement scores. In one study, this product also decreased the need for steroids, resulting in complete withdrawal of steroid therapy without exacerbation of disease in 80% of patients (93390). However, most patients in these studies were not treated with other standard therapies for ulcerative colitis, such as immunosuppressants and aminosalicylic acids. Subgroup analyses by dose suggest that the effective dose of this product is at least 1 gram daily; however, taking 3-4 grams daily may be more effective (93389,105728). In patients not responsive to mesalamine, some preliminary clinical research suggests taking LT-02 (Lipid Therapeutics GmbH), a modified-release formula of phosphatidylcholine, 3.2 grams daily for 12 weeks, improves symptoms of ulcerative colitis. Overall disease activity was improved by 52%, compared with 33% in those taking placebo. The effects on remission rate and mucosal healing were unclear; however, response rates were increased from 60% in the placebo group to 83% in the phosphatidylcholine group. In an 8-week follow-up, relapse was also less likely in patients treated with this product (93387).

POSSIBLY INEFFECTIVE

• Hepatitis A. Taking phosphatidylcholine orally does not seem to reduce serum bilirubin or liver enzyme levels in patients with hepatitis A (5225).
• Infant development. Clinical research suggests that taking phosphatidylcholine (PhosChol, Nutrasal) 5 grams daily, containing choline 750 mg daily, from 18 weeks' gestation to 90 days postpartum does not improve cognitive function in the infant at 10-12 months of age when compared with corn oil placebo (93386).
• Peritoneal dialysis. Taking phosphatidylcholine orally does not seem to improve ultrafiltration in peritoneal dialysis (5222).
• Tardive dyskinesia. Taking phosphatidylcholine orally does not seem to improve tardive dyskinesia (5223).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Preliminary clinical research suggests that topical application of a cream containing niacinamide and linoleic acid-rich phosphatidylcholine (4% niacinamide-phospholipidic; N-PHCL emulsion) once daily for 12 weeks appears to improve skin hydration and reduce acne lesions and inflammation when compared with a 1% clindamycin cream or a carrier-only cream in patients 15 years and older with moderate acne (93388).
• Alcohol-related liver disease. Preliminary clinical research suggests that taking polyunsaturated phosphatidylcholine 6 grams daily for 24 months does not increase survival compared to placebo in patients with acute alcoholic hepatitis (68843).
• Dementia. Population research in a sample of 1259 men in Finland found that those in the highest quartile of daily phosphatidylcholine intake have a 28% lower risk of being diagnosed with dementia than those in the lowest quartile, over a mean follow-up of about 22 years (103178).
• Fatty deposits. Preliminary clinical evidence suggests that subcutaneous injections of phosphatidylcholine can reduce localized fatty deposits on the chin, thigh, hips, abdomen, back, neck, and elsewhere, based on subjective visual assessments (15621,15625,15627). Improvements appear to last for 2-3 years or longer (15621,15627). In one study, phosphatidylcholine injections markedly or moderately reduce localized fatty deposits on the face in about 80% of patients for a period of up to 3 years based on subjective patient self-assessment (15621). The findings of these studies are severely limited by poor study quality.
• Hepatic encephalopathy. Clinical research suggests that taking polyunsaturated phosphatidylcholine 1050 mg daily for 6-8 weeks, either orally or through a nasogastric tube, does not improve recovery from encephalopathy compared with control in patients with acute or subacute liver failure. However, polyunsaturated phosphatidylcholine seems to reduce mortality compared to control in patients with subacute, but not acute, liver failure (68835).
• Hepatitis B. Clinical research using phosphatidylcholine for hepatitis B show conflicting results (5224,5226).
• Hepatitis C. Preliminary clinical research suggests that taking the polyunsaturated form of phosphatidylcholine orally, in combination with interferon, seems to help reduce liver enzymes in patients with chronic hepatitis C (5226).
• Hyperlipoproteinemia. Clinical research suggests that taking polyunsaturated phosphatidylcholine 1.8 grams daily for 28 days in combination with clofibrate does not significantly reduce total cholesterol, triglycerides, or phospholipids compared to clofibrate alone in patients with primary hyperlipoproteinemia of Fredrickson Types II or IV. However, taking the combination of polyunsaturated phosphatidylcholine plus clofibrate seems to significantly attenuate the relative increase in low-density lipoprotein (LDL) cholesterol compared to clofibrate alone (68840).
• Lipoma. An anecdotal report suggests that injecting a phosphatidylcholine solution directly into a lipoma can shrink the tumor by about 35%. However, in this report a major inflammatory reaction occurred, resulting in undesirable fibrotic changes to the tissue and eventual surgical excision of the lipoma (15622).
• Memory. Preliminary clinical evidence shows that taking a single dose of phosphatidylcholine 25 grams (PC-55, TwinLab) can improve some measures of memory in healthy college students (5228).
• Nonalcoholic fatty liver disease (NAFLD). Preliminary clinical research shows that taking phosphatidylcholine 600 mg orally three times daily for 24 weeks qualitatively improves liver echogenicity and structure on an ultrasound scan, suggesting a reduction in hepatic steatosis. There is also a small decrease in liver function test values, but with considerable variability both at baseline and at 24 weeks (103176,103177). Preliminary clinical evidence also suggests that taking a combination of the milk thistle constituent silybin, phosphatidylcholine, and vitamin E (Realsil, Instituto Biochimico Italiano) orally twice daily for 12 months improves liver function tests (LFTs) and liver histology in people with NAFLD (63244).
• Periorbital fat pad herniation. Preliminary clinical research suggests that injecting a phosphatidylcholine solution markedly reduces lower eyelid fat pads in people with bulging fat pads due to herniation. In some people, benefits appeared to last for a period of 9 months to 2 years or longer (15623,15628). More evidence is needed to rate phosphatidylcholine for these uses.

(Read more about PHOSPHATIDYLCHOLINE)

POSSIBLY SAFE ...when used orally and appropriately. L-arginine has been used safely in clinical studies at doses of up to 24 grams daily for up to 18 months (3331,3460,3595,3596,5531,5532,5533,6028,7815,7816)(8014,8473,13709,31943,91195,91196,91963,99264,99267,110380)(110387). A tolerable upper intake level (UL) for arginine has not been established, but the observed safe level (OSL) of arginine intake established in clinical research is 20 grams (31996). ...when used intravenously and appropriately. Parenteral L-arginine is an FDA-approved prescription product (15). ...when used topically and appropriately. L-arginine appears to be safe when 5 grams is applied as a topical cream twice daily for 2 weeks or when a dentifrice is used at a dose of 1.5% w/w for up to 2 years (14913,96806). ...when inhaled, short-term. L-arginine appears to be safe when inhaled twice daily at a dose of 500 mg for up to 2 weeks (96807).

CHILDREN: POSSIBLY SAFE
when used orally in premature infants and children (8474,32286,96803,97392,110391). ...when used intravenously and appropriately (97392). Parenteral L-arginine is an FDA-approved prescription product (15). ...when used topically, short-term. A dentifrice containing L-arginine appears to be safe when used at a dose of 1.5% w/w for up to 2 years in children at least 3.7 years of age (96806). ...when inhaled, short-term. L-arginine appears to be safe when inhaled twice daily at a dose of 500 mg for up to 2 weeks in children at least 13 years of age (96807).

CHILDREN: POSSIBLY UNSAFE
when used intravenously in high doses. Parenteral L-arginine is an FDA-approved prescription product (15). However, when higher than recommended doses are used, injection site reactions, hypersensitivity reactions, hematuria, and death have occurred in children (16817).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term. L-arginine 12 grams daily for 2 days has been used with apparent safety in pregnancy during the third trimester (11828). L-arginine 3 grams daily has been taken safely during the second and/or third trimesters (31938,110379,110382). ...when used intravenously and appropriately, short-term. Intravenous L-arginine 20-30 grams daily has been used safely in pregnancy for up to 5 days (31847,31933,31961,31978).

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about L-ARGININE)

LIKELY SAFE ...when used orally and appropriately. The pantothenic acid derivative calcium pantothenate has a generally recognized as safe (GRAS) status for use in food products (111258). While a tolerable upper intake level (UL) has not been established, pantothenic has been used in doses of 10-20 grams daily with apparent safety (15,6243,111258) ...when applied topically and appropriately, short-term. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and its derivatives are safe for use in cosmetic products in concentrations up to 5.3% (111258). Gels or ointments containing a derivative of pantothenic acid, dexpanthenol, at concentrations of up to 5%, have been used safely for up to 30 days (67802,67806,67817).

POSSIBLY SAFE ...when applied intranasally and appropriately, short-term. A dexpanthenol nasal spray has been used with apparent safety up to four times daily for 4 weeks (67826). ...when applied in the eyes appropriately, short-term. Dexpanthenol 5% eyedrops have been used with apparent safety for up to 28 days (67783). ...when injected intramuscularly and appropriately, short-term. Intramuscular injections of dexpanthenol 500 mg daily for up to 5 days or 250 mg weekly for up to 6 weeks have been used with apparent safety (67822,111366).

CHILDREN: LIKELY SAFE
when used orally and appropriately (15,6243). Calcium pantothenate is generally recognized as safe (GRAS) when used as a food additive and in infant formula (111258). However, a tolerable upper intake level (UL) has not been established (15,6243). ...when applied topically and appropriately (67795,105190,111262). Infant products containing pantothenic acid and its derivatives have been used safely in concentrations of up to 5% for infant shampoos and 2.5% for infant lotions and oils. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and derivatives are safe for use in topical infant products. (111258).

PREGNANCY: LIKELY SAFE
when used orally and appropriately. The daily adequate intake (AI) during pregnancy is 6 mg (3094).

LACTATION: LIKELY SAFE
when used orally and appropriately. The daily adequate intake (AI) during lactation is 7 mg (3094).

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POSSIBLY SAFE ...when used orally and appropriately. Large doses up to 30 grams per day for 6 weeks (5223) and smaller doses of up to 6 grams daily for up to 24 months have been well tolerated (68839,68843,105728). ...when used subcutaneously and appropriately, short-term. Some research suggests that subcutaneous injections of 0.2 mL to 5 mL of a 5% phosphatidylcholine solution do not cause significant serious adverse effects when doses are administered up to five times and spaced apart by 2-4 weeks (15621,15623,15624,15625). ...when used topically as an emulsion also containing niacinamide for up to 12 weeks (93388).

PREGNANCY: POSSIBLY SAFE
when used orally from 18 weeks of gestation at doses of up to 5 grams daily (93386)

LACTATION:
Insufficient reliable information available; avoid using.

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ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of L-arginine and ACE inhibitors may increase the risk for hypotension and hyperkalemia.  Details Combining L-arginine with some antihypertensive drugs, especially ACE inhibitors, seems to have additive vasodilating and blood pressure-lowering effects (7822,20192,31854,31916). Furthermore, ACE inhibitors can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients (32213,32218). Theoretically, concomitant use of ACE inhibitors with L-arginine may increases the risk of hyperkalemia.

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of L-arginine and ARBs may increase the risk of hypotension and hyperkalemia.  Details L-arginine increases nitric oxide, which causes vasodilation (7822). Combining L-arginine with ARBs seems to increase L-arginine-induced vasodilation (31854). Furthermore, ARBs can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients (32213,32218). Theoretically, concomitant use of ARBs with L-arginine may increases the risk of hyperkalemia.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.  Details Preliminary research suggests that L-arginine infusions reduce platelet aggregation in humans (32260,31864,32239,32220,32257,32263,32276,32188). The clinical significance of this effect is unclear.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.  Details Preliminary clinical research shows that L-arginine decreases blood glucose levels in patients with type 2 diabetes (31964,32085,31964,104225).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.  Details L-arginine increases nitric oxide, which causes vasodilation (7822). Clinical evidence shows that L-arginine can reduce blood pressure in some individuals with hypertension (7818,10636,31871,32201,32167,32225,31923,32232,110383,110384). Furthermore, combining L-arginine with some antihypertensive drugs seems to have additive vasodilating and blood pressure-lowering effects (7822,20192,31854,31916).

ISOPROTERENOL (Isuprel) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concurrent use of isoproterenol and L-arginine might result in additive effects and hypotension.  Details Preliminary clinical evidence suggests that L-arginine enhances isoproterenol-induced vasodilation in patients with essential hypertension or a family history of essential hypertension (31932).

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically concomitant use of potassium-sparing diuretics with L-arginine may increases the risk of hyperkalemia.  Details Potassium-sparing diuretics can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients (32213,32218).

SILDENAFIL (Viagra) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of sildenafil and L-arginine might increase the risk for hypotension.  Details In vivo, concurrent use of L-arginine and sildenafil has resulted in increased vasodilation (7822,8015,10636). Theoretically, concurrent use might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported (105065).

TESTOSTERONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of L-arginine and testosterone might have additive effects.  Details In clinical research, L-arginine increases the level of testosterone in male patients with erectile dysfunction (102586,104222). The clinical significance of this finding is unclear.

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General ...Oral, intravenous, and topical L-arginine are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, nausea, diarrhea, headache, insomnia, flushing.
Intravenously: Excessively rapid infusion can cause flushing, headache, nausea and vomiting, numbness, and venous irritation.

Cardiovascular ...L-arginine taken orally by pregnant patients in a nutrition bar containing other antioxidants was associated with a 36% greater risk of palpitations when compared with a placebo bar (91197). It is unclear if this effect was due to L-arginine, other ingredients, or other factors.

Dermatologic ...Orally, arginine can cause flushing, rash, and hives (3460,32138,102587,104223). The skin reactions were likely of allergic etiology as oral L-arginine has been associated with eosinophilia (32138). In one case report, intravenous administration caused allergic reactions including urticaria, periorbital edema, and pruritus (11830). Excessively rapid infusion of L-arginine has caused flushing, local venous irritation, numbness. Extravasation has caused necrosis and superficial phlebitis (3330,16817).

Gastrointestinal ...Orally, L-arginine has been reported to cause nausea, diarrhea, vomiting, dyspepsia, gastrointestinal discomfort, and bloating (1363,31855,31871,31972,31978,32261,90198,91197,96811,99243)(102587,102592).
Orally, L-arginine has been reported to cause esophagitis in at least six adolescents. Symptoms, which included pain and dysphagia, occurred within 1-3 months of treatment in most cases (102588). There are at least two cases of acute pancreatitis possibly associated with oral L-arginine. In one case, a 28-year-old male developed pancreatitis after consuming a shake containing 1.2 grams of L-arginine daily as arginine alpha-ketoglutarate. The shake also contained plant extracts, caffeine, vitamins, and other amino acids. Although there is a known relationship between L-arginine and pancreatitis in animal models, it is not clear if L-arginine was directly responsible for the occurrence of pancreatitis in this case (99266).
Intravenously, excessively rapid infusion of L-arginine has been reported to cause nausea and vomiting (3330,16817).

Musculoskeletal ...Intravenous L-arginine has been associated with lower back pain and leg restlessness (32273). Orally, L-arginine has been associated with asthenia (32138).

Neurologic/CNS ...Orally, L-arginine has been associated with headache (31855,31955,32261,91197,102587,102592), insomnia, fatigue (102587,102592), and vertigo (32150,102592).

Oncologic ...In breast cancer patients, L-arginine stimulated tumor protein synthesis, which suggests stimulated tumor growth (31917).

Pulmonary/Respiratory ...When inhaled, L-arginine can cause airway inflammation and exacerbation of airway inflammation in asthma (121). However, two studies assessing oral L-arginine in patients with asthma did not detect any adverse airway effects (31849,104223).

Renal ...Intravenously, L-arginine has been associated with natriuresis, kaliuresis, chloruresis, and systemic acidosis (32225). Orally, L-arginine can cause gout (3331,3595).

Other ...Orally, L-arginine has been associated with delayed menses, night sweats, and flushing (31855).

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General ...Orally, pantothenic acid is generally well tolerated. Topically and intramuscularly, dexpanthenol, a synthetic form of pantothenic acid, seems to be well tolerated.
Most Common Adverse Effects:
Topically: Burning, contact dermatitis, eczema, irritation, and itching related to dexpanthenol.

Cardiovascular ...There is one case of eosinophilic pleuropericardial effusion in a patient taking pantothenic acid 300 mg per day in combination with biotin 10 mg per day for 2 months (3914).

Dermatologic ...Topically, dexpanthenol has been associated with itching, burning, skin irritation, contact dermatitis, and eczema (67779,67781,67788,111258,111262). Three cases of allergic contact dermatitis have been reported (111260,111261).

Gastrointestinal ...Orally, pantothenic acid has been associated with diarrhea (67822,111258).

(Read more about PANTOTHENIC ACID)

General ...Phosphatidylcholine is generally well tolerated when used orally, subcutaneously, or topically. Orally, bloating, diarrhea, altered taste, nausea, vomiting, sweating, and itching have been reported with phosphatidylcholine (5229,63244,68843,93389,93390,105728). Ingesting large amounts of around 30 grams daily is associated with a higher incidence of gastrointestinal upset and diarrhea (5223). Subcutaneously, pain, burning, itching, tenderness to touch, bruising, edema, nodules, hematoma, and erythema at the injection site have been reported with phosphatidylcholine (1562,15623,15624,15625,15626,15627,15628). High subcutaneous doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624). Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissues changes (15622).

Dermatologic ...When taken orally, phosphatidylcholine may increase sweating (5229) and itching (63244). When given subcutaneously, phosphatidylcholine can cause pain, burning, itching, tenderness to touch, bruising, edema, and erythema at the injection site. The pain, itching and erythema usually resolve within 2 days of treatment; however localized tenderness can last longer (15623,15624,15626,15627,15628). Edema and bruising usually resolve within 10 days of treatment (15621,15623,15625). Some people can also develop nodules or hematoma at the injection site. This usually resolves within 30 days (15627).

Gastrointestinal ...Ingesting large amounts of phosphatidylcholine (30 grams per day) can cause gastrointestinal upset and diarrhea (5223). However, bloating, diarrhea, altered taste, nausea, and vomiting have been reported with smaller doses (63244,68843,93389,93390,105728). Although moderate subcutaneous doses do not usually cause systemic side effects, high doses exceeding 1.2 grams of phosphatidylcholine can cause nausea and abdominal pain in some people (15624).

Musculoskeletal ...Injecting phosphatidylcholine directly into a lipoma can result in a significant inflammatory response and undesirable fibrotic tissue changes (15622).

(Read more about PHOSPHATIDYLCHOLINE)