The amino acid that prevents endothelium dysfunction:

Arginine Holds Your
Heart Together

By controlling many of the factors that keep it strong

By Will Block

Obesity is linked with a great many comorbidities, including type 2 diabetes, hypertension, and cardiovascular diseases (CVDs). According to the World Health Organization, globally in 2015, 2.3 billion people aged 15 years or older will be overweight, and more than 700 million people will be obese (when the calculations are finalized).

What It Means to Be Obese

The National Institutes of Health classifies overweight and obesity according to body mass index (BMI), waist circumference (WC), and the risks of associated diseases. The terms “overweight” and “obese” refer to body weight that’s greater than what is considered healthy for a certain height. Obesity, especially when the buildup of fat is around the abdomen, is associated with increased risks of morbidity and mortality, as well as CVDs. Importantly, obesity is an independent risk factor for CVDs, a class of diseases that involves the heart or blood vessels.1

What CVDs Embrace

CVDs include coronary artery diseases (CAD) such as angina and myocardial infarction (aka, a heart attack). Other CVDs are stroke, cardiomyopathy, heart arrhythmia, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, hypertensive heart disease, rheumatic heart disease, and venous thrombosis. [Thank you, Wikipedia]


High levels of free radicals are
produced in patients with CVDs.


Obesity is associated with tenacious insulin resistance, which can lead to hyperglycemia, lipid disorders, oxidative stress, and arterial hypertension. Chronic hyperglycemia plays an important role in the cause and progression of arterial pathology. The relationship between hyperglycemia and oxidative stress has been confirmed. High levels of free radicals are produced in patients with CVDs. These factors are responsible for the pathogenesis of and endothelium dysfunction associated with CVDs.

Arginine Helps Prevent Endothelium Dysfunction

Many studies have demonstrated the use of L-arginine (hereafter arginine) for the prevention of many diseases associated with endothelium dysfunction, such as atherosclerosis and diabetes. In fact, one study found that long-term oral arginine administration improved peripheral and hepatic insulin sensitivity in type 2 diabetic patients.2 The researchers reported that arginine treatment significantly improved peripheral and hepatic insulin sensitivity in patients with type 2 diabetes and that this might have been caused by nitric oxide (NO) synthesis, which uses arginine as a substrate.


The proven antioxidative properties of
arginine have been very significant.


The proven antioxidative properties of arginine have been very significant. In vivo, arginine had an inhibitory effect on superoxide radicals and increased the concentrations of available antioxidants, which protect low-density lipoprotein (LDL) from oxidation, by decreasing the production of O2- (superoxide anion).

­­Despite Obesity, Arginine is Beneficial

Few studies have assessed the potential positive effects of arginine supplementation on CVD-associated indices in obese patients. The aim of a new study1 was to evaluate the influence of arginine supplementation on anthropometric and blood biochemical indices associated with CVDs in obese individuals. BMI is calculated by weight in pounds/(height in inches)2 x 703). Although developed nearly 200 years ago, BMI is not actually a measure of adiposity, but an imprecise mathematical estimate. It cannot distinguish lean body mass from fat mass. However, BMI is popular because of its convenience, safety, and minimal cost, and thus is widely used.


Weight loss can downregulate the
expression of TNF-alpha and improve
insulin sensitivity.


The Measurements Taken

In the study, which was done in Iran at Shiraz University of Medical Sciences, the researchers set out to evaluate the influence of 8-week oral arginine supplementation on body mass index (BMI), waist circumference (WC), triceps skinfold (TS), subscapular skinfold (SS), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma fasting blood sugar (FBS), glycated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and malondialdehyde (MDA) in patients with (individual BMI values > 29.9 or WC values > 40 inches in men or > 35 inches in women).

Patients and Methods

Ninety obese patients were included in a single-blind randomized controlled trial. The subjects were non-smokers and teetotalers (they did not drink). Patients were randomized to receive either of two amounts of arginine (1 or 2 g trice daily) or placebo for 8 weeks. That’s a total of 3 or 6 g/day.

Anthropometric and biochemical indices, dietary intake, and blood pressure values were measured at the baseline and after the 8-week intervention.

At the end of the study significant decreases in anthropometric parameters, blood pressure (SBP, DBP), FBS, HbA1c, LDL, MDA, TG, and TC and a significant increase in HDL were observed in the intervention groups, compared to the control group. In the control group, no significant differences were found between the baseline and end-of-intervention measurements.

Arginine Improves Risk Factors

The prevalence of CVDs is increasing dramatically, and prior studies have shown that arginine supplementation can improve some associated risk factors. The Iranian study evaluated the effect of arginine supplementation at 3 or 6 g/day on BP, as well as some anthropometrical and biochemical factors associated with CVDs, in obese subjects. The study revealed significant decreases in anthropometrical parameters. Also, at the end of the study comparison of pre- and post-intervention measurements within each arginine group revealed significant decreases in weight, BMI, WC, TS, systolic blood pressure (SBP), and SS in the group taking 3 g/day of arginine, and significant decreases in all parameters in the group taking 6 g/day of arginine.

Previous studies have reported excess activation of tissue necrosis factor (TNF)-alpha in obese patients. Indeed, the role of TNF-alpha in the pathogenesis of insulin resistance has been demonstrated in obese patients. This cytokine reduces insulin activity in various tissues. In adipose tissue, TNF-alpha overstimulates lipolysis by activating hormone-sensitive lipase and increases insulin resistance by increasing serine phosphorylation and inhibiting tyrosine phosphorylation in insulin receptor substrate-1 (IRS-1), thus decreasing insulin receptor activity; in muscle cells, this cytokine also reduces the expression of GLUT-4.


Larger HDL particle size are
associated with exceptional longevity.


The Benefits of Weight Loss

Weight loss can downregulate the expression of TNF-alpha and improve insulin sensitivity.3 Also, catabolic changes in HDL concomitant with weight loss might be related to an increase in HDL particle size, which might itself be consequent to a reduction in the pool of plasma very LDL TGs available for exchange with HDL. Larger HDL particle size are associated with exceptional longevity.4


Arginine supplementation was found
to be associated with significant
decreases in SBP and DBP in patients
with essential hypertension.


Weight reduction increases adiponectin, which can inhibit hepatic lipase activity. This might account for the partial increase in HDL, and likely accounts for the increased HDL levels observed after weight loss. Our study observed significant decreases in BP parameters (SBP, DBP) after the 8-week intervention. Similar findings were reported in previous studies.

Arginine Lowers Blood Pressure

Arginine supplementation was found to be associated with significant decreases in SBP and DBP in patients with essential hypertension. This may be the result of impaired arginine transport and the risk of hypertension development, possibly indicating an association between defective arginine/NO pathway signaling and the onset of hypertension.


This study suggests arginine as a
promising, safe, and beneficial
supplement with beneficial effects on
many risk factors of CVDs.


As obesity can cause insulin resistance, elevated FBS and HbA1c levels were expected as typical consequences in the participants. The present study showed significant improvements in FBS and HbA1c in groups treated with arginine. In a previous study, an FBS level > 109.8 mg/ dL and a 1% increase in HbA1c were found to increase the risk of death from ischemic heart disease by 38% and 30%, respectively.

The availability of NO can also improve glucose metabolism. NO by itself can influence muscle glucose metabolism, In a previous study, insulin-resistant obese rats were found to harbor a defect in the NO metabolic pathway. Furthermore, NO increased glucose transport both in the absence and in the presence of insulin in rat muscles in vitro.

Arginine restores NO bioavailability through the competitive inhibition of NO synthase (NOS) by asymmetric dimethylarginine (ADMA), the main endogenic inhibitor of NOS. ADMA was found to improve the clinical statuses of patients with CVDs by reducing the generation of O2-.


Arginine restores NO bioavailability
through the competitive inhibition of
NO synthase (NOS) by asymmetric
dimethylarginine (ADMA), the main
endogenic inhibitor of NOS.


Protecting LDL from Oxidation

In a previous study, arginine increased the amount of available antioxidants, which protect LDL from oxidation. Free radicals cause lipid oxidation as well as biomembrane damage, which is reflected by lipid peroxidation and consequently increases the levels of MDA.

The present study observed a significant decrease in the MDA level. Previous studies have reported similar results with arginine supplementation, including improved antioxidant statuses indicated by an increased total antioxidant status, glutathione and superoxide dismutase levels, and circulating plasma ascorbic acid levels, all of which have been shown to protect against peroxidative lipid damage; therefore, increased cell membrane permeability and decreased lipid oxidation lead to decreased MDA levels.


Oral arginine supplementation
improves anthropometric parameters,
blood pressure values, and some
blood biochemical indices associated
with cardiovascular disease
prevention.


The researchers recommend additional clinical trials with larger sample sizes and longer intervention periods to facilitate a better understanding of the role of arginine supplementation for weight management in obese people at risk of CVDs. This study suggests arginine as a promising, safe, and beneficial supplement with beneficial effects on many risk factors of CVDs.

In conclusion, an 8-week course of oral L-arginine supplementation decreased anthropometric parameters and blood pressure values and improved some biochemical factors associated with CVDs in patients with BMI values indicating obesity or visceral obesity.

Oral arginine supplementation improves anthropometric parameters, blood pressure values, and some blood biochemical indices associated with cardiovascular disease prevention.

References

  1. Dashtabi A, Mazloom Z, Fararouei M, Hejazi N. Oral L-Arginine Administration Improves Anthropometric and Biochemical Indices Associated With Cardiovascular Diseases in Obese Patients: A Randomized, Single Blind Placebo Controlled Clinical Trial. Res Cardiovasc Med. 2015 Dec 29;5(1):e29419. doi: 10.5812/cardiovascmed.29419. eCollection 2016 Feb. PubMed PMID: 26889456; PubMed Central PMCID: PMC4750008.
  2. Piatti PM, Monti LD, Valsecchi G, Magni F, Setola E, Marchesi F, Galli-Kienle M, Pozza G, Alberti KG. Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care. 2001 May;24(5):875-80.
  3. Cartier A, Cote M, Bergeron J, Almeras N, Tremblay A, Lemieux I, et al. Plasma soluble tumour necrosis factor-alpha receptor 2 is elevated in obesity: specific contribution of visceral adiposity. Clin Endocrinol (Oxf). 2010;72(3):349–57.
  4. Barzilai N, Atzmon G, Schechter C, Schaefer EJ, Cupples AL, Lipton R, Cheng S, Shuldiner AR. Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA. 2003 Oct 15;290(15):2030-40.


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

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