Fight Aging!

In today's open access paper, the authors review the evidence for the practice of calorie restriction to reduce blood pressure and cardiovascular disease risk in human subjects. The raised blood pressure of hypertension occurs with age, the result of molecular damage such as cross-linking of blood vessel tissue that impairs elasticity and inflammatory signaling that impairs smooth muscle function. As blood vessels stiffen, the feedback mechanisms governing blood pressure run awry. Lifestyle choices such as lack of exercise and weight gain are also influential on blood pressure.

Hypertension is a major mechanism of aging. It causes increased pressure damage to tissues throughout the body, such as through rupture of small blood vessels, accelerates the progression of atherosclerosis, and pushes cardiac tissue into harmful remodeling that leads to heart failure.

Several human studies of calorie restriction have been conducted since the turn of the century, including those under the CALERIE program. The practice of calorie restriction reliably improves long term health in later life, improving metrics such as blood pressure to a degree comparable to or greater than most drug treatments are capable of achieving. Only with the advent of senolytic treatments to clear senescent cells in aged tissues, and other rejuvenation therapies that will follow, will medical technology begin to provide greater reliable benefits when intervening in the aging process.

Effects of Caloric Restriction Diet on Arterial Hypertension and Endothelial Dysfunction

The calorie restriction diet (CRD) innovative approach consists of a chronic reduction in daily caloric intake of about 25-30% compared to the normal caloric intake, without any exclusion of food groups. Although this regimen is not standardized, numerous studies show its effectiveness. The mechanism of action by which caloric restriction prolongs the life span is not fully understood yet. Recent studies have shown that CRD can determine repair of damaged DNA and decrease fat mass, systolic blood pressure (SBP) and diastolic blood pressure (DBP) values, and the production of free radicals. The results obtained from the CRD can occur quickly, but they can mitigate in case of its suspension.

The CRD would seem to exert a beneficial effect against arterial hypertension (AH) and for this reason represents a useful tool for its clinical management. An important study conducted in this regard was the CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy). The CALERIE study was a randomized controlled trial with a two-year follow up. This study was divided in two phases: CALERIE-1 and CALERIE-2. CALERIE-1 study was performed to assess the possible effects induced by a reduction of 10-30% of caloric intake on body composition parameters and lipid profile after 6 and 12 months in a population of middle-aged non-obese subjects. CALERIE-1 results showed an improvement in lipid and glycemic profile and a reduction in body weight (BW) and fat mass.

CALERIE-2 was the largest multi-center study on CRD. A total of 220 subjects were enrolled randomly with a 2:1 allocation into two subgroups: 145 in the CRD group and 75 in the ad libitum group. The CRD group followed 25% caloric restriction for two-years. After two years of diet treatment, cardiometabolic risk factors such as low-density lipoprotein cholesterol (LDL-c), total cholesterol / high-density lipoprotein cholesterol (HDL-c) ratio, SBP and DBP decreased. Moreover, serum biomarkers such as C-reactive protein, insulin sensitivity index and metabolic syndrome score were reduced. Moreover, BW was significantly lower in the CRD group when compared to the ad libitum group (average weight loss in CRD group was 7.5 kg vs average BW increase of 0.1 kg in ad libitum group).

This data showed that a period of two-years of CRD was able to decrease cardiometabolic risk factors in middle-aged non-obese subjects. For this reason, it is possible to consider CRD as nutritional therapeutic approach to enhance life expectancy and reduce the onset of chronic non-communicable diseases such as diabetes mellitus, cancer, chronic kidney disease, and AH, among others.

Other studies have been conducted to investigate the role of CRD in the control of AH. In particular, a study performed on caloric restriction (25%), with two years follow-up, evaluated the possible reduction of CV risk factors and insulin resistance in non-obese subjects and whether the results obtained were maintained over time or were limited to the period study. The authors showed a significant weight loss associated to a decrease in SBP and DBP and an improvement in other parameters, such as lipid profile and insulin resistance. These improvements, with the exception of insulin sensitivity, appeared to be maintained over time.