Updated: Sep 28, 2022
Arginine is a semi-essential or conditionally essential amino acid, meaning our body can make it but our diet is the primary source of our needed supply. For whatever reason, if our body utilizes more than we make, our body doesn't compensate, which is why we must attain arginine from our diet. Interestingly, there are no established RDA guidelines for the quantity we should attain from our diet or our daily recommended need. Clearly, some individuals are at risk for deficiency, which primarily results from poor diet.
Another name for #arginine is, 2-Amino-5-guanidinopentanoic acid. It is predominantly found in protein-containing foods and as such, red meat, poultry, fish, and dairy products are its primary food source; however, arginine is also abundant in seeds and nuts. It is best known for its effects on the vascular system and when deficient, muscle weakness and #fatigue are significant. Chronic infections are also apparent when arginine is insufficient.
Nitric Oxide Precursor
Arginine is a precursor to nitric oxide so it has become quite popular for those seeking athletic performance enhancement therapies; however, the benefits of arginine supplementation are vast. Any condition which may benefit from enhancement of nitric oxide is a potential indication for intravenous supplementation of arginine. Consider that athletic performance is one significant indication, but because of its impact on the vascular system, improvement in blood pressure, peripheral arterial disease, intermittent claudication, and congestive heart failure can also be realized. This would also extend to interstitial cystitis, improvement in immune function, #erectiledysfunction, metabolic support, pregnancy-induced hypertension, #preeclampsia, sickle cell disease, reducing waist circumference, wound healing, and necrotizing enterocolitis, which is almost exclusive to premature infants. There are even more indications with less supporting evidence or even unclear benefits, but know that the potential here is grand.
Arginine was original approved to be administered intravenously by the FDA (1973) to assist the pituitary in releasing human growth hormone, but has since been used off-label for a plethora of other indications. Beyond athletic performance, arginine has also been useful in treating high ammonia concentrations in individuals with urea cycle disorders.
Arginine is synthesized from citrulline producing nitric oxide, proline, glutamate, creatine, and agmatine (Wu et al., 2009). It stimulates the release of insulin from the pancreas and plays a significant role in immune function. It is known for stimulating killer cell activity for phagocytosis and is required for normal growth and proliferation of lymphocytes. It is also a potent vasodilator.
Arginine converts ammonia to urea so it can be excreted by the kidneys, clearing nitrogenous waste from our bodies. Those who are a bit hyperamoneous may either have an arginine deficiency or lack an enzyme for urea cycle breakdown.
Athletic Performance and IV Infusions with Arginine
A meta-analysis of eleven randomized clinical trials (2021) found that arginine supplementation increased VO2 max compared to the control group. Another study in 2020, also a systematic review and meta-analysis, evaluated the effects on aerobic and anaerobic performance and found arginine supplementation could improve performance tests, even identifying effective dosing and timing of this supplementation. Ultimately, supplementation prior to performance can significantly improve athletic goals. Plasma concentrations of post-exercise NOx has shown to be significantly higher in supplemented groups and cycle performers, for example, report less muscle weakness following performance. Time to exhaustion has even shown to improve after a single dose of arginine.
Cardiovascular Effects with Arginine
Meta-analysis have demonstrated that arginine reduces blood pressure with pooled estimates of 5.4 mmHg systolic and 2.7 mmHg diastolic. Several other studies have found similar results, including studies specifically evaluating intravenous arginine infusions. Interestingly though, in one study, arginine was offered to subjects who had been taking ACE-inhibitors or blood pressure drugs, along with diuretics, and their blood pressures were not improving. Adding the arginine was successful in reducing both systolic and diastolic pressures.
Peripheral arterial disease has also shown to be beneficially impacted by intravenous arginine supplementation. A 2017 (Kashyap, et al.) study found serum nitrogen oxides increased by 85 percent following supplementation despite extensive atherosclerosis, and endothelial function was enhanced. Intermittent claudication is also improved with arginine supplementation, including walking distance and increased walking speed.
Congestive heart failure has evidence suggesting intravenous arginine is likely beneficial in the literature as well. Heart rate has also been shown to decrease, along with mean systemic arterial pressure and systemic vascular resistance. Researchers also found increased right atrial pressure, cardiac output, and stroke volume but what clients recognize is an improvement in their exercise tolerance. Angina has had some conflicting evidence; it has been helpful in several studies, but not all. In fact, some say it is unlikely helpful. This is a mystery that is not yet understood.
Interstitial Cystitis and IV Arginine
This is a tough condition to treat, so intravenous arginine is a potential option but further studies are needed. Older studies are available, which support the use of arginine for IC, but not a lot more recently which means professional groups recognize the potential here, but aren't overwhelmingly acknowledging a clear connection. A study in 2000, smaller study group, found the arginine group had significant reduction in their overall symptom score. Another study in 1999, showed again that symptoms, including pain and urgency, were reduced in the treatment group. A third, smaller study in 1997, showed arginine offered decreased voiding discomfort, less abdominal pain and vaginal/urethral pain, as well as decreased urinary frequency during the day and night. The evidence is clearly older, but there is likely good benefit here especially because there just aren't a lot of options otherwise.
Immune Function is Beneficial with IV Arginine
Studies have found that when people are septic, they have lower arginine levels than in those who are not septic. Natural killer cells are also reduced, as are cell proliferation and viability. Overall, cytotoxicity is significantly reduced. Further evaluation has revealed that persons with HIV are improved with arginine supplementation. There is enough evidence, that it is now recommended in Europe as a treatment with trauma and surgery. Arginine also has demonstrated to have a synergistic effect on dental caries compared with placebo or fluoride alone (Li et al, 2015).
Erectile Dysfunction and Arginine Infusions
Yep! Makes sense though because erectile dysfunction is almost always related to vascular function and early stages of diabetes. A 2019 review by Rhim et al. evaluated ten random control trials specific to arginine and found that doses ranging from 1,500 to 5,000mg significantly improved erectile dysfunction compared with placebo or no treatment. Significant improvements were achieved in overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function. Another review from 2019 (Koolwal et al) found that arginine alone and arginine combined with pine bark, which our practice has been recommending for years, significantly improved erectile dysfunction, including decreasing time to achieve erection and increased the duration of the erection. Sperm quality and #sperm mobility were also improved.
Arginine acts differently than the pharmaceuticals typically provided for erectile dysfunction, but more similar to the regimen we have offered men in our practice for quite a few years. This addresses the underlying root cause which not only helps with sexual performance, but helps improve vascular health and ward off impending diabetes and heart disease. Total testosterone levels improved alongside arginine and #tadalafil supplementation in one study.
Arginine for Metabolic Support
Certainly this is how arginine is helping those with erectile dysfunction, but essentially, arginine improves glycemic control, improving fasting blood #glucose levels and serum #insulin in randomized control trials. Studies have also evaluated various supplement regimens on #PCOS and obesity with significant results, in spite of not also implementing lifestyle or dietary changes. Total cholesterol, HDL, triglycerides, plasma insulin levels and HOMA index were improved after 12 and 24 weeks.
Another randomized double-blind placebo-controlled study (Suliburska et alk, 2014) found that significant increases in insulin sensitivity and zinc levels can be realized with just 9 grams of arginine for six months. A significant adiposity reduction was found in mice who were supplemented with arginine, as well as improvement in glucose tolerance.
The studies here regarding metabolic support are significant and each with similar outcomes. There is a great deal of anti-diabetic activity, even improved liver glycogen levels, improved carbohydrate metabolizing enzymes reverting back to normal, and reduced diabetes related to pancreatic damage when arginine is supplemented. Compared with placebo, L-arginine increases insulin sensitivity and adiponectin. The results here are tremendous; arginine infusions may be an excellent treatment modality for many.
Pre-eclampsia and PIH
While #pregnancy is not the typical client for IV clinics, there is pretty solid evidence supporting the use of L-arginine for pregnant women with hypertension. Randomized control trials have found improved gestational weights in the fetus of those undergoing treatment (Garg et al., 2019), and reduced systolic and diastolic blood pressures (Arikawe, 2019). Ultimately those with lower levels of arginine prove to have worse pregnancy outcomes and those with more normal levels and more uneventful pregnancies (Sirenden, 2020).
A rather interesting finding, in my mind, is the Vadillo-Ortega et al., (2011) study in which women were provided L-arginine 6.6 grams within Heart Bars manufactured by Nellson Nutraceuticals, which also offered antioxidant vitamins, daily starting at 14 to 32 weeks of pregnancy and continuing until delivery resulted in a reduction in the incidence of pre-eclampsia by 44 percent in a population otherwise at high risk. Another 2016 study, found 3 grams of arginine daily starting in the twentieth week of pregnancy reduced the risk of pre-eclampsia by 74 percent when compared to placebo, as well as offered higher birth weights and less preterm births.
Two studies have evaluated intravenous administration specifically, and the first, by Facchinetti et al, in 1999, utilized 30 grams of arginine in a one-time dose and found systolic blood pressures were lowered by 5 mmHg and diastolic readings by 11 mmHg which compared to baseline pregnant women with either preeclampsia or hypertension. Huge, right? The second found IV arginine given 20 grams daily for five days decreased SBP and DBP by about 2 percent when compared to placebo, also Facchinetti et al, 2007.
Reproductive Effects & Arginine
There is some thought that L-arginine may stimulate motility and metabolism of sperm from asthenospermic men (Srivastava & Agarwal, 2010). Pine bark, which was mentioned previously for the treatment of erectile dysfunction, combined with L-arginine, and L-citrulline and roburins, can improve sperm quality and enhance sperm volume and concentration, motility, vitality and morphology. Fertility index rose to normal during treatment. Women having experienced infertility were also demonstrating positive outcomes in fertility, with improved uterine blood flow and endometrial thickness.
Sickle Cell Disease
Arginine has shown to be likely beneficial for this significantly painful disease. A 2013 study found a 54 percent reducing in the need for parenteral opioid use and lower pain scores at discharge, which also offered shorter hospital stays (Morris et al.) Another study found levels of NO were increased which reduced pain frequency (Eleuterio, 2019), and a double blind random control trial found a mean rate of decline in worst pain scores was faster in the arginine group and shorter time to crisis resolution, with overall shorter hospital stay.
Weight Loss Effects
The evidence is less supportive here; however, a meta-analysis of twelve studies found significant reduction in overall body mass index, waist circumference, and fat mass although body weight was not greatly impacted. It would seem however, that overall body composition improved which is our ultimately goal, to simply having a lower overall body weight. A systematic review and meta-analysis of eight randomized trials did find significant reduction in waist circumference, but no significant results on weight or BMI. When supplements were provided beyond eight weeks however, the BMI was decreased significantly.
Individuals with metabolic syndrome were also evaluated in a double-blind randomized trial and there was significant decrease in the mean percentage of fat mass with only 5 grams daily by mouth. Hurt et al., (2014) found 3 grams of arginine three times each day, by mouth, for twelve weeks along with lifestyle modifications reduced their weight circumference by 6.4 cm and weight decreased by about six pounds. Overall, arginine may not be a primary approach to weight loss, but certainly could be a supportive adjunct therapy.
Wound Healing and Arginine
A multitude of studies have found arginine in acute care settings improved wound healing. Often this is even used topically for healing, but for this post, the focus is a bit more intravenous focused. Studies have found pressure ulcers with arginine supplementation are significant reduced in size and healing is improved (Schneider & Yahia, 2019). A 2021 study found the effect of arginine and glutamine on wound healing improved the speed of wound healing (Arribas-Lopez et al.). Another study found complete wound healing in otherwise non-healing wounds after supplementation with arginine, with wound surface area ranging from 24 percent to 88 percent reduction within two to twelve weeks. Additional protein, zinc, and vitamin C can further support this effort.
The potential here is significant for use of arginine in various treatment plans and offering this intravenously can have improved outcomes as it can be more bioavailable for a plethora of people with less than optimal gut health. Feel free to visit one of our Meet the Doc sessions or send us an email if you have any questions. Otherwise, feel free to book a new client visit to get your full health history and physical, so we can determine the best wellness regimen for you, including intravenous therapy.