Arginine Enhances Immune Function
Surgery patients benefit from arginine, omega-3 fatty acids, and RNA

he immune system is one of the great marvels of human biology. It stands at constant attention, ready to protect us against foreign invaders in all their guises: bacteria, viruses, fungi, and parasites alike. White blood cells (so called because they do not contain hemoglobin, as red blood cells do, and thus look colorless under the microscope) provide the primary defense against potential microbial infections. These cells can readily respond to invading microorganisms to immobilize them and stop their proliferation.

There are a number of different types of white blood cells circulating in your body, and they employ an array of sophisticated techniques to prevent infections. Among the most important of these cells are the lymphocytes, of which there are two kinds: B cells (which mature in bone marrow) and T cells (which mature in the thymus gland). B cells make antibodies, molecules that recognize foreign agents and mark them for destruction. T cells are of two principal kinds: Helper T cells work with other cells of the immune system to stimulate their activity (helper T cells are targeted for destruction by the HIV virus, by the way). Killer T cells (also called cytotoxic T cells) attack foreign invaders; they are able to change their cell surface so as to make themselves more sensitive to different agents.

Macrophages and neutrophils are the garbage disposals of the immune system: they gobble up foreign viruses and bacteria to prevent widespread infections. All of these cells, and many others, work together to ensure that infectious agents don't make themselves too comfortable in your body.

As happens with so many activities in the body, the efficiency of the immune system typically declines with age, and older individuals are thus increasingly susceptible to life-threatening infections. Sadly, the same infections they may have been able to defeat just a few years earlier may now overpower their immune systems and make them very ill.

Thus it is especially gratifying to realize that the immune system can be boosted through nutritional supplementation. This fact has been known for many years, but new evidence is found in The Lancet, a prestigious British medical journal, in which Dutch researchers have recently reported that surgery patients who were given a combination of arginine, omega-3 fatty acids, and RNA for five to ten days before their operations were far less likely to develop postsurgical infections, and they thus had an improved outlook for recovery following the procedure.1 (We will discuss this study below.)

The amino acid arginine has long been used as an immunonutrient to improve the immune function in compromised individuals, such as those suffering burns, sepsis (poisoning by the presence of pathogens in the blood or tissues), or trauma, and it is often given to cancer and HIV patients as well.2 Arginine is considered a "conditionally essential" amino acid, which means that under certain circumstances, such as those just mentioned, your body cannot synthesize adequate amounts of it, and you need to obtain it from dietary sources.

Traumatic events, including surgery, increase the body's need for arginine, which is required for protein synthesis and the production of white blood cells. Specifically, arginine is important in the formation of polyamines, molecules that newly formed B cells and T cells require during their rapid growth and proliferation in the early stages of an infection. Arginine is also involved in wound repair and thus helps the body to heal more quickly.

In the immune system, omega-3 fatty acids are important for the production of signaling molecules called eicosanoids and prostaglandins. These molecules are released by immune cells and are used to mount a swift response against foreign invaders.3

The role of the RNA (from yeast cells) in the immunonutrient formulation is to provide molecules called purines and pyrimidines, which result from the digestion of RNA. Once transported by the bloodstream to the body's cells, these molecules undergo chemical reactions to form four different kinds of nucleotides, the building blocks of both DNA and RNA. (The process is analogous to the way in which our digestion of proteins from other organisms results in amino acids, which are then transported to our cells and reassembled into human proteins.) The rapid growth and proliferation of the immune cells, which of course contain DNA and RNA, is facilitated by the supplemental amounts of these purines and pyrimidines.4

There is a long, convincing history supporting the benefits of arginine in individuals with a compromised immune system, including cancer patients, HIV patients, and patients recovering from surgery. A recent review article reports that doses as low as 12.5 grams per day of arginine can improve immune function in hospitalized patients; the benefits include improved T-cell counts, lower infection rates, and shortened hospital stays.5

Arginine is a "conditionally
essential" amino acid:
under certain circumstances, your
body cannot synthesize adequate
amounts of it, and you need to
obtain it from dietary sources.

One of the earliest studies using arginine/omega-3 fatty acids/RNA to improve immune function was performed at the University of Minnesota in 1991 and involved 20 patients (aged 21-80) from the hospital's intensive care unit.6 For 7-10 days, eleven of the patients received supplementation with a solution of 12.5 g of arginine, 11.1 g of menhaden oil rich in omega-3 fatty acids, and 1.25 g of RNA per liter of nutrient formula, while nine patients received placebo. The solution was delivered via a feeding tube inserted into the patients' duodenum. This study was designed solely to investigate the biological mechanisms underlying immunonutrient supplementation, and it demonstrated that supplementation specifically enhanced the proliferation of lymphocytes.

Doses as low as 12.5 grams per
day of arginine can improve
immune function; the benefits
include improved T-cell counts,
lower infection rates, and
shortened hospital stays.

Experiments conducted on mice have helped to clarify the role that arginine in particular plays in amplifying the immune response.7 When specific white blood cell populations were investigated under controlled laboratory conditions, it was demonstrated that not all white blood cells respond to arginine treatment. Killer T cells, for example, proliferate much more rapidly when arginine is abundantly present than when it is in short supply.

Major surgery involves a number of factors that stress the immune system. Chief among these are the use of anesthesia and blood transfusions and the potential for postoperative malnutrition. Thus it may not be surprising that supplementation with arginine/omega-3 fatty acids/RNA, representing three major constituents of all cells (proteins, lipids, and nucleic acids), dramatically enhances immune-cell response under this very stressful situation. In fact, a number of medical studies emphasize the benefit of this type of supplementation in enhancing immune function.

Killer T cells proliferate much
more rapidly when arginine is
abundantly present than
when it is in short supply.

In a study of 85 patients (41 in the treatment group, 44 in the control group) who underwent gastrointestinal surgery to remove malignant tumors, dietary supplementation with arginine/omega-3 fatty acids/RNA for 7 days after the surgery improved immune function compared with placebo.8 On average, the patients were given about 17.5 g of arginine, 2.4 g of omega-3 fatty acids, and 1.8 g of RNA daily. Infections and wound complications occurred in only 11% of patients in the treatment group, compared to 37% of those in the control group. In addition, the mean length of the hospital stay was significantly shorter in the treatment group (15.8 days) than in the control group (20.2 days). Obviously, in addition to improved health, the treatment group reaped significant financial savings (especially at today's costs) by having their hospital stay shortened by about 4 1/2 days.

A number of other studies have confirmed the benefits of supplementation with arginine/omega-3 fatty acids/RNA. In one study involving 42 patients who had undergone gastrointestinal surgery for cancer, it was found that the number of T cells, including helper T cells and activated T cells,* increased.9 On the tenth day after surgery, the patients receiving the supplement posted an activated T-cell count of 132 cells per milliliter, versus 81 cells/ml in the control group - an improvement of 63%; by day 16 after surgery, the improvement was 92%. Helper T-cell counts were unchanged in the supplemented group for the first three days following surgery. Thereafter they increased dramatically, however: compared with the control group, they were 27% higher by day 7, 34% higher by day 10, and 49% higher by day 16.

*Activated T cells include a variety of T-cell types - including killer T cells - that divide rapidly and are primed for destroying foreign pathogens. Most T cells in the circulatory system are not "activated," and they are incapable of protecting against infections.

In addition to improved health,
the treatment group reaped
significant financial savings by
having their hospital stay
shortened by about 4 1/2 days.

In the two surgical studies just discussed, supplementation occurred after the surgery. Researchers at the University of Amsterdam wanted to know if supplementation with arginine before surgery would also be beneficial; they found that it was.1

The study involved 50 patients (aged 70 or older) at high risk of infection after cardiac surgery. For 5-10 days before surgery (the average was 7.2 days), half the patients received an average daily supplementation of 12.5 g of arginine, 3.3 g of omega-3 fatty acids, and 1.3 g of RNA, while the other half received placebo. Three different laboratory tests were performed to measured the patients' immune response, and the cells from the supplemented patients performed significantly better in all of them. More to the point as far as the patients' actual condition was concerned, the postsurgical infection rate was dramatically less in the treatment group (18%) than in the control group (55%).

In all the studies cited above, the use of arginine/omega-3 fatty acids/RNA was established as a safe and effective treatment. The benefits of arginine, however, are not limited to the immune system. Medical research has revealed that arginine supplementation supports cardiovascular health and kidney health and even helps to reverse erectile dysfunction in some patients (see sidebar). With respect to improving kidney health, daily supplementation with 15 g of arginine leads to an improved ability to filter wastes and maintain normal water and sodium balance in patients with chronic heart failure.10

Arginine Helps with Erectile Dysfunction

Nitric oxide, an important metabolic product of arginine, is a signaling molecule that plays a vital role in the cardiovascular system. Through its action on the smooth endothelial cells lining our arteries, it causes the arteries to relax and dilate, thereby increasing blood flow. When this occurs in the penile arteries, the result is to facilitate erections.

As it turns out, sildenafil (better known by its trade name, Viagra®) does pretty much the same thing (but without the other benefits of arginine) - for a while, that is. A recently published article suggests that with long-term use, sildenafil loses its potency (so to speak).1

Eighty-two patients were followed for up to two years to determine whether sildenafil was effective over the long term. After two years, only 43 of the men were still using sildenafil, and of those, 16 (37%) reported that the dose had to be doubled (from 50 mg to 100 mg) to remain effective. Significant loss of effectiveness occurred at an average of 11 months after initial use, but it ranged from 1 to 18 months.

Of the 39 men who stopped using sildenafil, 14 reported that it worked well initially but eventually lost its effectiveness. An additional 11 men reported that it never worked at all for them, and 10 of these 11 finally abandoned hope and stopped using it as well. These findings show that, although sildenafil may be effective for some men, not everyone sings its praises.

Enter arginine. When men with erectile dysfunction were given either 5 grams per day of arginine or a placebo for a period of 6 weeks, arginine supplementation clearly yielded superior results.2 Of the treated patients, 31% were satisfied with their sexual performance, as opposed to only 12% in the control group.

Unlike sildenafil, arginine supplementation is not associated with adverse effects (remember that men with cardiovascular problems are strongly advised not to take sildenafil), and there is no indication that arginine becomes less effective over time.


  1. El-Galley R, Rutland H, Talic R, Keane T, Clark H. Long-term efficacy of sildenafil and tachyphylaxis effect. J Urol 2001;165:927-31.
  2. Chen J, Wollman Y, Chernichovsky T, et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double blind, randomized, placebo-controlled study. BJU Int 1999;83:269-73.

To investigate the role that arginine supplementation plays in cardiovascular health, 45 elderly patients (aged 67-82) were assigned to a treatment group (30 g of arginine aspartate, equivalent to 17 g of free arginine) or a control group for a 2-week trial.11 When blood lipid levels were measured at the end of the trial, it was found that arginine supplementation had decreased total cholesterol from 231 milligrams per deciliter to 207 mg/dL, while the control group remained essentially unchanged, from 226 to 225 mg/dL. The levels of HDL (high-density lipoprotein, the "bad cholesterol") did not change in either group. However, triglycerides decreased significantly in the treatment group (17.4%), with no significant change in the control group.

The immune system isn't perfect, but it's pretty close. Every day, you are exposed to an incredibly large number of potentially harmful microorganisms - we're talking billions! - yet you usually don't get infected, because you have a healthy immune system (think of it as your body's SWAT team, which can be mobilized at a moment's notice), which does its best to protect you from harm. So make sure that you nourish your immune system appropriately, and you will be well protected and richly rewarded.


  1. Tepaske R, te Velthuis H, Oudemans-van Straaten HM, et al. Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial. Lancet 2001;358:696-701.
  2. PDR for Nutritional Supplements. Medical Economics Company, Inc., Montvale, NJ, 2001, pp. 248-54.
  3. O'Leary MJ, Coakley JH. Nutrition and immunonutrition. Br J Anaesth 1996;77:118-27.
  4. Kulkarni AD, Rudolph FB, Van Buren CT. The role of dietary sources of nucleotides in immune function: a review. J Nutr 1994;124:1442S-46S.
  5. Field CJ, Johnson I, Pratt VC. Glutamine and arginine: immunonutrients for improved health. Med Sci Sports Exerc 2000;32:(Suppl) S377-88.
  6. Cerra FB, Lehmann S, Konstantinides N, et al. Improvement in immune function in ICU patients by enteral nutrition supplemented with arginine, RNA, and menhaden oil is independent of nitrogen balance. Nutrition 1991;7:193-9.
  7. Ochoa JB, Strange J, Kearney P, et al. Effects of L-arginine on the proliferation of T lymphocyte subpopulations. J Parenteral Enteral Nutr 2001;25:23-9.
  8. Daly JM, Lieberman MD, Goldfine J, et al. Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in patients after operation: immunologic, metabolic, and clinical outcome. Surgery 1992;112:56-67.
  9. Kemen M, Senkal M, Homann H-H, et al. Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact®. Crit Care Med 1995;23:652-9.
  10. Watanabe G, Tomiyama H, Doba N. Effects of oral administration of L-arginine on renal function in patients with heart failure. J Hypertens 2000;18:229-34.
  11. Hurson M, Regan MC, Kirk SJ. Metabolic effects of arginine in a healthy elderly population. J Parenteral Enteral Nutr 1995; 19:227-30.

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