Arginine Improves Energy Efficiency

Arginine Boosts Insulin Sensitivity and Cardiovascular Function
Major age-related health problems can benefit from this amino acid

nsulin is as vital a molecule as there is. We can't live without it. The older we get, though, the harder it is for our bodies to make efficient use of our precious insulin. The problem is called insulin resistance. It's a common feature of aging, but one we can combat through the enlightened application of our scientific knowledge.

The amino acid arginine, source of nitric oxide (NO), which enhances insulin sensitivity and dilates blood vessels.

We have learned that there are many ways to resist insulin resistance. Number one is regular exercise, which, not at all coincidentally, is also the number one way to prevent, and often cure, a host of other ills associated with aging. Exercise is king. Number two is a healthy diet, with plenty of fresh fruits and vegetables. And number three (we don't mind being third after those two) is savvy supplementation with natural nutrients that we just don't get enough of even with a healthy diet.

One such nutrient is arginine, the champion of amino acids when it comes to biochemical versatility: no other amino acid can match its broad spectrum of benefits. Now we have learned that arginine can help improve our insulin sensitivity, which is the same as diminishing our insulin resistance. We'll look at the evidence, but first, a primer on what insulin actually does. Let's start with a homely analogy.

Imagine that you live in the snowy north, in a sturdy but aging house that's showing some signs of wear and tear - not everything works quite as well as it used to, and some things are in need of repair. The house is heated by a coal-fired furnace, and you've laid in a generous supply of coal, piled high for the winter. Now the fire is burning low, and the house feels a bit chilly. You need more heat. You go to the furnace, grab the shovel, and reach for the latch on the furnace door. But . . . it won't open!

Uh-oh. You fiddle with it, you whack at it, but it resists. Finally it opens, and you shovel some coal in. Whew! The heat pours out, and you're OK - for now. But what about a few hours from now, when you'll need to do it again? Will the recalcitrant latch resist again? Will you have to spend more and more of your energy just trying to get into that furnace so as to produce more energy? Where will that lead?

In your body, the chemical energy and heat that keep you alive come from glucose molecules. Glucose (often called blood sugar) is the principal product of digestion of carbohydrates and, to a lesser extent, of fats and proteins as well. It is your body's primary fuel, the molecule that gets "burned" with the oxygen you inhale. Think of every cell in your body as a tiny "furnace" into which you must shovel an unending supply of glucose molecules to keep the metabolic fires stoked. The "door" to the cellular furnace is a channel through the cell membrane, and the "latch" on that door is a highly discriminating protein receptor site designed to respond only to the molecule that acts as the "shovel" for glucose. That molecule is the hormone insulin, which is produced by the pancreas.

If there were no insulin, the glucose would just sit there, like a pile of cold coal, unable to provide any energy. Glucose needs that insulin "shovel" to go where it will do some good. But the shovel is no good if the latch won't open. And that is what happens in insulin resistance. The insulin shows up, but the receptor refuses to recognize it, thus preventing the channel from opening and allowing the glucose through. The more this occurs, the more the cell function is impaired and slowed. Eventually, the cell will die. And if enough of them die . . . well, you know the rest.

The above is an oversimplification, of course. The actual chain of events is very complex and involves many different kinds of molecules and chemical reactions and feedback loops. But the bottom line is that, unless we find ways to counteract insulin resistance, we will age faster and die sooner than is necessary. Insulin resistance is a harbinger - and, ultimately, a symptom - of type 2, or age-related, diabetes mellitus. This disease, a chronic metabolic disorder, is also called non-insulin-dependent diabetes mellitus (NIDDM) because a lack of insulin is not the problem (that problem is the hallmark of type 1, or juvenile-onset, diabetes mellitus).

The main result of this study was
that insulin sensitivity increased by
34% in the arginine group (vs. 4%
in the control group), and it was
attributed to the arginine.

No, with insulin resistance, there’s plenty of insulin - even too much, often - but our bodies are insufficiently sensitive to it. That has two dire consequences: (1) not enough glucose in the cells, where it is needed, and (2) too much glucose in the bloodstream, where excessive amounts can do a great deal of damage. As with many other biologically powerful compounds, glucose requires a fine balancing act to maintain our health, and anything that upsets that balance threatens not just our health but our very life. Diabetes, for example, is a major risk factor for cardiovascular disease.

A team of researchers in Italy and England has just published the results of a study showing that insulin sensitivity can be enhanced by an increase in the neurotransmitter nitric oxide (NO), induced by administering its source, arginine.1 The test subjects were 12 lean adults (8 men and 4 women), average age 58, with type 2 diabetes, who had good metabolic control and were being treated for their disease with diet alone.

The protein hormone insulin. As proteins go, insulin is relatively small. It contains 460 atoms in 51 amino acid units (including one arginine) linked in two polypeptide chains that are linked to each other. This is the molecular "shovel" that enables glucose molecules (which are much smaller) to enter our cells.

For a one-month control period, the patients were monitored while on their usual diet. They were then randomized into two groups. One group was treated with diet and a placebo (orally three times daily) for two months. The second group was treated in exactly the same way for one month, but for the second month (i.e., the third and last month of the study), they received arginine (in the form of arginine aspartate) - without knowing it, of course - instead of placebo. The dose was 3 g of arginine aspartate orally three times daily. This was the lowest dose that would elicit NO synthesis without changing insulin secretion by the pancreas, which arginine is known to stimulate.

The patients were evaluated periodically for insulin sensitivity, following standardized insulin infusions under carefully controlled circumstances. For purposes of comparison, insulin sensitivity was also evaluated in ten normal subjects who underwent identical infusions.

The main result of this study was that insulin sensitivity increased by 34% in the arginine group (vs. 4% in the control group), and it was attributed to the arginine. In the arginine group (but not the control group), there was a significant increase in blood levels of a molecule called cGMP, which is an indicator of NO synthesis from arginine. NO is a vasodilator, i.e., it dilates blood vessels, thereby decreasing blood pressure and increasing blood flow. And sure enough, the study showed a significant decrease in systolic blood pressure (the first, higher value when blood pressure is recorded), and there was also an increase in blood flow in the forearms of the arginine-treated patients (but not the controls). Both factors confirmed that there had been an increase in NO production.

It is interesting to note that the blood levels of cGMP in the type 2 diabetic patients were significantly lower than in normal individuals and that the arginine treatment completely normalized these levels (meaning that it had normalized NO activity). Nonetheless, arginine did not completely normalize insulin sensitivity in these patients. This suggests that the origins of insulin resistance probably entail other factors - genetic, environmental, or metabolic - as well as NO activity.

Arginine's effects (through its release of NO) on decreasing blood pressure and increasing blood flow are also central to its role in helping to protect against heart disease. They explain the ability of arginine to improve exercise capacity, even in patients with congestive heart failure (a chronic weakening of the heart’s pumping capacity).2 And they explain arginine's ability to decrease pulmonary vascular resistance (a measure of the resistance of blood vessels to the flow of blood through them) in the lungs of patients with pulmonary hypertension.3 (Pulmonary refers to the lungs.)

OK, but what is pulmonary hypertension? It's high blood pressure in the lungs - not a good thing. It comes about gradually as a consequence of untreated respiratory failure. And what is that? Respiratory failure is a condition in which oxygen levels in the blood become dangerously low, or carbon dioxide levels become dangerously high. It results from an inadequate exchange of oxygen and carbon dioxide between the lungs and the blood, or from an inadequate movement of air in and out of the lungs. And those defects can be caused by many different diseases or conditions that affect one's ability to breathe properly. A few examples are chronic bronchitis, asthma, emphysema, muscular dystrophy, and obesity.

Let's review that chain of events in the reverse order (the order in which the events actually occur). Someone with one of those breathing-impairment conditions may develop respiratory failure, which is manifested as poor oxygenation of the blood. This can lead to pulmonary hypertension as the cardiovascular system tries to compensate for the oxygen deficiency. The pulmonary hypertension comes about through a constriction of the blood vessels, and this increases the pulmonary vascular resistance, because the now narrower inner diameter of the blood vessels tends to impede blood flow.

Insulin Resistance and Diabetes

As if you needed reminding, obesity is a monumental public health problem: it is estimated to affect about 58 million Americans, and it contributes to about 300,000 deaths annually from heart attack, stroke, diabetes, and cancer. In our self-indulgent society, obesity is the result of inadequate exercise and the typical "Western diet" that is rich in fat and refined sugars, and low in fiber.

These lifestyle errors are a near-perfect setup for developing insulin resistance, which is central to the development of type 2, or adult-onset, diabetes. It is no coincidence that about 90% of all the victims of this terrible disease are obese. And the risk increases with age in any case.

The typical type 2 diabetic has high levels of insulin, because the pancreas keeps churning it out in a desperate attempt to keep up with the excessive blood levels of glucose - not knowing, of course, that the body's cells have become increasingly resistant to the insulin and are thus creating a relative insulin deficiency. The victims produce up to four times as much insulin as normal individuals, yet their glucose levels can still be too high - the defining characteristic of diabetes.

The long-term consequences of diabetes can be devastating. They include accelerated atherosclerosis, leading to a sharply increased risk of heart attack and stroke, as well as serious harm to the kidneys, eyes, genitals, and other organs. Poor peripheral circulation due to diabetes can cause severe damage, leading to gangrene, and damage to the nerves can cause weakness and pain. The list goes on and on. Do not let this happen to you!

All in all, this is bad news, because regardless of what caused the respiratory failure in the first place, pulmonary hypertension will damage the blood vessels, further impairing oxygenation. And poor oxygenation will eventually cause heart failure and other malfunctions of the heart and brain. Finally, death pays a visit.

But didn't we say that arginine could help with pulmonary hypertension? Yes - and a recently published study from Japan gives new evidence of that fact.4 The study was a randomized, double-blind, placebo-controlled trial on 19 patients (average age 49) with pulmonary hypertension. Oral arginine supplementation was followed by hemodynamic (blood-flow) testing and cardiopulmonary exercise testing, using a number of different measurement techniques that need not concern us. Let's just see the results.

Arginine's effects (through its release of NO)
on decreasing blood pressure and increasing
blood flow are also central to its role in
helping to protect against heart disease.

With a dose of 0.5 g of arginine per 10 kg of body weight (equivalent to 4 g for a 175-lb person), there was a 9% drop in pulmonary arterial pressure and a 16% drop in pulmonary vascular resistance 60 minutes after administration, indicating improved blood flow. For evaluation of exercise capacity, a dose of 1.5 g of arginine per 10 kg of body weight (equivalent to 12 g for a 175-lb person) was administered daily for one week. The patients were then tested while riding an exercise bicycle. With arginine (but not placebo) there was an 8% increase in peak oxygen consumption, associated with a 12% increase in peak work load, indicating improved cardiovascular function.

Thus arginine is shown, yet again, to be beneficial to cardiovascular health, both directly through its effect on cardiovascular function and indirectly through its effect on insulin sensitivity. There are many ways in which you can take advantage of the health benefits of arginine to suit your lifestyle and overall needs.


  1. Piatti PM, Monti LD, Valsecchi G, Magni F, Setola E, Marchesi F, Galli-Kienle M, Pozza G, Alberti KGMM. Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diab Care 2001 May;24(5):875-80.
  2. Rector TS, Bank AJ, Mullen KA, Tschumperlin LK, Sih R, Pillai K, Kubo SH. Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure. Circulation 1996;93:2135-41.
  3. Mehta S, Stewart DJ, Langleben D, Levy RD. Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension. Circulation 1995;92:1539-45.
  4. Nagaya N, Uematsu M, Oya H, Sato N, Sakamaki F, Kyotani S, Ueno K, Nakanishi N, Yamagishi M, Miyatake K. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 2001 Mar;163(4):887-91.

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