Vitamin-obesity paradox

Column-Dr Ramon Abarquez photo

Medicine is Not an Exact Science

Ramon F. Abarquez, Jr., MD, EFACC, FAsCC, FPCP, FPCC, CSPSH

SINCE synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased, leading to increased prevalence of obesity.

Vitamin-obesity paradox

Paradoxically, obesity is often associated with low levels of fasting serum folate and vitamin D but high erythrocyte folate concentrations. High erythrocyte folate oxidation is related to long-term excess folic acid intake, while increased folate oxidation products may increase folate degradation. Obesity increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate.

Likewise, obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity occurs in a low excretory reserve capacity (low birth weight/preterm birth) and/or in a low sweat gland activity (black race and physical inactivity).

Thus, obesity could be compensatory to chronic vitamin poisoning due to excessive vitamin intake, a vitamin paradox in obesity from the perspective of vitamin homeostasis. (Zhou, World J Diabetes. 2015 Aug 25;6(10):1158-67)

Individuals with normal body weight by body mass index (BMI) and high body fat percentage show a high degree of metabolic dysregulation, wherein “normal weight obesity” but with a significantly higher risk of metabolic syndrome, cardiometabolic dysfunction and with higher mortality. Recently, coronary artery disease patients with normal BMI and central obesity have the highest mortality risk as compared to other adiposity patterns. Therefore, a need for an updated definition of obesity based on adiposopathy and not merely on body weight. (Oliveros, Prog Cardiovasc Dis. 2014 Jan-Feb;56(4):426-33) Is the risk merely obesity or due to co-morbidities and organ damage?

Obesity paradox in hypertension

Obesity is a significant public health problem, associated with several co-morbidities and complications with a U-shaped curve (significantly worse prognosis among underweight and morbidly than in obese individuals). The association between overweight or grade I obesity and cardiovascular mortality is not clear. (Haberka, Pol Arch Med Wewn. 2014;124(12):731-9)

European Working Party on High Blood Pressure in the Elderly Trial showed a U shape relation between BMI and cardiovascular and non-cardiovascular endpoints. (Romero-Corral, ancet. 2006; 368: 666-678) However, a sub-analysis of the results of the Systolic Hypertension in the Elderly Program performed in 3975 subjects without a history of cancer, stroke, and myocardial infarction (MI) showed no associations between BMI and death and stroke prevalence in the group treated with placebo. Moreover, in subjects treated with low dose antihypertensive drugs, the U shaped relation between nutritional status and mortality showed the lowest probability of death for a BMI cut off point of 26.0 kg/m2for men and 29.6 kg/m2 for women. (Wassertheil-Smoller Arch Intern Med. 2000 Feb 28;160(4):494-500)

Recently, a sub-analysis of the data from the INternational VErapamil SR Trandolapril Study (INVEST), involving 22,572 elderly patients diagnosed with essential hypertension and CAD, revealed that the incidence of the primary outcome of death, nonfatal MI, and nonfatal stroke was lower among overweight and obese subjects compared with normal weight ones. In contrast, a higher risk of the primary outcome, all cause and CVD mortality, and nonfatal stroke in underweight individuals compared with normal weight ones was observed.

However, it should be noted that under weight patients were older, were current smokers, and frequently had end stage chronic kidney disease, heart failure (HF), MI, stroke, peripheral vascular disease.(Hastie, Eur Heart J. 2010; 31: 222-226) The results of a meta analysis including cohort studies, which enrolled 250,152 patients with CAD, found a higher risk of CVD and all cause mortality in underweight subgroups and lower in patients with overweight and grade I or II obesity than in normal weight subgroups, while the risk of CVD mortality was significantly higher and all cause mortality risk was similar in morbidly obese compared with normal weight subgroups. (Akin, J Am Coll Cardiol Cardiovasc Interv. 2012; 5: 162-169)

Obesity-hypertension paradox concerns

In an industrialized society, the increase in obesity incidence has led to an increase in premature morbidity and mortality rates, relationships with increased incidence of hypertension, dyslipidemia, type 2 diabetes mellitus, cardiovascular disease with an increase in mortality.

However, obese individuals with these conditions may have better outcomes than their lean counterparts. Most studies supporting this paradox are cross-sectional without regards to quantity or type of adiposity, the disease severity, and co-morbidities. Although BMI is an indicator of the amount of body fat, adipocytes that are highly functional have good fuel storage capacity while adipocytes found in visceral obesity, are poorly functioning, laden with macrophages, and causing low-grade inflammation. Individuals with high BMI may be physically fit and have a lower mortality risk when compared with individuals with a lower BMI and poorly functioning adiposity. Thus, the complexity of adipose tissue and its location, function, metabolic implications, and role in cardiovascular morbidity and mortality in the “obesity paradox” may reflect “a lack of understanding of the complex pathophysiology of obesity and the association between adiposity and cardiovascular disease.” (Goyal, Cardiol Rev. 2014 Jul-Aug;22(4):163-70.)

 Vital Signs Issue 86 Vol. 4, April 1-30 2016