Hearts are important in Poland …

Arginine Reduces Fatigue
and Insulin Resistance

A continuous flow of Polish research supports
the health benefits of the amino acid arginine

By Will Block

P

oland has been the source of a significant amount of arginine research. Back in 2004, Polish researchers investigated whether oral administration of arginine would improve exercise capacity in 17 patients with mild to moderate congestive heart failure.1 The patients received 3 g of arginine or placebo 3 times daily (9 g/day total) for 7 days. Testing was done on a treadmill according to a standard protocol, and the patients were asked to exercise until fatigue or dyspnea (difficulty in breathing) forced them to stop. After a 7-day washout period, the arginine and placebo regimens were reversed, and the tests were repeated—thus all the patients served as their own controls.

Whereas the controls had an average exercise duration of 70 seconds on the treadmill, the arginine treatment yielded an average duration of 99 seconds on the treadmill—a 41% improvement. The researchers attributed this effect primarily to improved peripheral vasodilation caused by increased NO production.

Arginine Boosts Antioxidant Activity in Atherosclerosis

Also in 2004, a study conducted in Poland suggests that arginine may exert an antioxidant effect indirectly through its action in promoting the antioxidant functions of other molecules.2 For 4 weeks, researchers administered two dosages of arginine (2 g or 4 g) three times daily, for a total of 6 g or 12 g daily. The patients were 32 hospitalized men and women, average age 60, with peripheral arterial disease, an atherosclerotic narrowing of the arteries in the legs that results in impaired circulation and pain in walking (called intermittent claudication in medical jargon). Arginine is known to be beneficial for this condition through its release of NO in the arteries, which improves endothelial function.


The arginine treatment yielded an
average duration of 99 seconds on the
treadmill—a 41% improvement.


Comparing the two groups at the end of the study, the researchers found (surprisingly) that the lower daily dose of arginine produced a much greater boost in the patients’ nitric oxide (NO) levels than the higher dose: with the higher dose, the levels were more than doubled over the baseline value, but with the lower dose, they were more than quadrupled.

The researchers also found that the patients’ total antioxidant status (i.e., the degree to which free radical activity was effectively suppressed in a specific blood test to measure this effect) was significantly increased in both groups of patients, with no statistically significant difference between them. The authors stated that the concurrent increase of NO levels and of total antioxidant status in these patients suggests the potential importance of orally administered arginine in terms of antioxidant activity.

Arginine Reduces Leg Pain and Walking Ability

Earlier in 1996, in a study conducted at the Collegium Medicum in Cracow, Poland, researchers evaluated 14 male patients aged 39–66 years (average 54) who had suffered from peripheral arterial obliterative disease and showed atherosclerotic lesions.3 The patients were hospitalized and received 3-hour intravenous infusions daily for 14 consecutive days: first a saline placebo for 7 days, then 12.6 grams of arginine for 7 days. The results were clinically significant improvements in terms of a treadmill test for leg pain and maximum walking distance, as well as for a variety of tests for blood circulation and composition.

Arginine Lowers Blood Pressure

In a more recent study, conducted at the Karol Marcinkowski University of Medical Science, Poznan, Poland, researchers enrolled 54 subjects (30 men, 24 women), otherwise healthy outpatients, who were divided based on blood pressure (BP) measurements into either a healthy control group (19 subjects) or a hypertensive treatment group (35 patients).4 The latter were freshly diagnosed with mild hypertension but had received no drugs or supplements prior to classification as hypertensive. Then the subjects were randomized to either 2 or 4 g of supplemental arginine three times daily (for a total of either 6 or 12 g/day) or placebo.


The results were clinically significant
improvements in terms of a
treadmill test for leg pain and
maximum walking distance, as well as
for a variety of tests for blood
circulation and composition.


Hypertension has long been thought to be one of the highest cardiovascular risk factors, because it represents a significant disturbance in the balance of vasomotor influences. It can cause disruptions that affect functional vasoconstriction, which can result in vessel closure and block microcirculation. Hypertension can also engender structural alterations that may affect the vascular endothelium so that there is decreased bioavailability of NO. Once called endothelium-derived relaxing factor, NO is responsible for establishing and maintaining resting vascular tone, regulating blood flow to meet the metabolic demands of tissue, and adapting vessel diameter to inflow volume. This has been upheld by long-term follow-up studies in the offspring of hypertensive patients.5 These have achieved a deeper understanding of the prognostic and genetic importance of reduced NO bioavailability in hypertension.

The study of arginine supplementation increased dramatically after the arginine/nitric oxide (oxide pathway was discovered. Among the findings of many of these studies was the demonstration of a beneficial effect of arginine on NO production and for reducing systemic blood pressure (BP). A review of these studies found that the results were not uniform and rather inconclusive, with dosages of arginine safely administered at even 30 g in single i.v. infusions. Studies of BP utilized oral doses of arginine ranging from 5–20 g daily, with most of them within the 6–9 g range. These data determined the choice of arginine administration regimens in the Polish study.

This study was designed to investigate the effects of arginine on BP, both for the purpose of hypertensive patient qualification and arginine therapy assessment. In large trials, lowering of BP by 2–3 mmHg by antihypertensive drugs is considered significant and leads to favorable outcomes, including the recognition that reducing even mild hypertension can lower the high risk of cardiovascular events, even when compounded by the presence of other risk factors.

Hypertension was diagnosed with mean awake BP values ≥135 mmHg systolic or 85 mmHg diastolic or average night-time values of ≥120 mmHg systolic or 70 mmHg diastolic or 24-h BP values ≥125 mmHg systolic or 80 mmHg diastolic. Physical and laboratory examinations, which included blood and urine tests, were normal. There were no cases of hyperlipidemia in the subjects. All patients had normal renal and liver function.

As Good as Blood Pressure Drugs

There were no adverse reactions in the subgroups receiving arginine, which was well tolerated—all subjects completed the study. The groups of patients receiving arginine for four weeks displayed BP reductions, with statistically significant reductions in the 24-hour and daytime BP parameters of the hypertensive patients, who received 4 g of arginine three times a day (12 g/day). Arginine lowered both systolic and diastolic BP, with a stronger hypotensive effect observed during the day. According to the researchers, the BP reductions were comparable to those achieved by antihypertensive drugs, with a mean daytime drop of 6 mmHg systolic and 5 mmHg diastolic. These reductions have been associated with substantial reductions in cardiovascular disease mortality, risk of stroke, and risk of myocardial infarction. Reductions in the subjects with normal blood pressure taking arginine did not reach statistical significance.


According to the researchers, the BP
reductions were comparable to those
achieved by antihypertensive drugs,
with a mean daytime drop of 6
mmHg systolic and 5 mmHg diastolic.


A Cardiovascular Boon for the Visceral Obese

In a more recent study, Polish researchers also at the University of Medical Science in Poznan undertook a study designed to evaluate the effects of L-arginine on the cardiovascular system and particularly on tumor necrosis factor alpha (TNF-alpha), one of the adipose tissue products which is know to worsen the pathogenesis of insulin resistance especially in those with visceral obesity.6

The researchers enlisted 60 patients with visceral obesity that were randomly assigned to either receive 9 g of L-arginine or placebo for 3 months. As controls, 20 healthy lean subjects were used. Anthropometrical measurements and blood biochemical analyses were performed at baseline and after 3-months. TNF-alpha and its soluble receptor 2 (sTNFR2) were assessed in both groups and insulin resistance in the participants was evaluated according to the homeostasis model assessment-insulin resistance (HOMA-IR) protocol.


Taking an L-arginine dose of
9 g for 3 months improves insulin
sensitivity in patients with visceral
obesity with no impact on TNF-alpha
concentration, which is known to
worsen insulin resistance.


At the end of the study, the concentrations of insulin, TNF-alpha, sTNFR2, and HOMA-IR level in both obese groups significantly exceeded these observed in the control. Basal TNF-alpha and sTNFR2 concentrations were positively correlated with basal body mass index (BMI), waist circumference, percent of body fat and HOMA-IR. Also, the researchers found that 3-month of L-arginine supplementation resulted in significant decrease of HOMA-IR and insulin concentration. Only an insignificant tendency to decrease of TNF-alpha and sTNFR2 was observed.

These results confirm the role of TNF-alpha in the pathogenesis of insulin resistance in patients with visceral obesity. Taking an L-arginine dose of 9 g for 3 months improves insulin sensitivity in patients with visceral obesity with no impact on TNF-alpha concentration, which is known to worsen insulin resistance.

References

  1. Bednarz B, Jaxa-Chamiec T, Gebalska J, Herbaczynska-Cedro K, Ceremuzynski L. L-Arginine supplementation prolongs exercise capacity in congestive heart failure. Kardiol Pol. 2004;60(4):348-53.
  2. Jablecka A, Checinski P, Krauss H, Micker M, Ast J. The influence of two different doses of L-arginine oral supplementation on nitric oxide (NO) concentration and total antioxidant status (TAS) in atherosclerotic patients. Med Sci Monit. 2004;10(1):CR29-32.
  3. Slawinski M, Grodzinska L, Kostka-Trabka E, Bieron K, Goszcz A, Gryglewski RJ. L-Arginine-substrate for NO synthesis—its beneficial effects in therapy of patients with peripheral arterial disease: comparison with placebo—preliminary results. Acta Physiol Hung. 1996; 84(4):457-8.
  4. Ast J, Jablecka A, Bogdanski P, Smolarek I, Krauss H, Chmara E. Evaluation of the antihypertensive effect of arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring. Med Sci Monit. 2010 Apr 28;16(5):CR266-71.
  5. Kelm M. The arginine-nitric oxide pathway in hypertension. Curr Hypertens Rep. 2003 Feb;5(1):80-6.
  6. Bogdanski P, Suliburska J, Grabanska K, Musialik K, Cieslewicz A, Skoluda A, Jablecka A. Effect of 3-month L-arginine supplementation on insulin resistance and tumor necrosis factor activity in patients with visceral obesity. Eur Rev Med Pharmacol Sci. 2012 Jun;16(6):816-23.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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