Vitamin D deficiency is the cause of common obesity
Introduction
Obesity is a clinical condition in which there is an above-normal mass of adipose tissue, usually defined by a Quetelet Index, or body mass index (BMI), of 30 kg/m2 or higher, and which is associated with increased morbidity and reduced mortality [1]. The prevalence and severity of obesity has increased in the past 30 years and is presently a public health concern in many countries. Common obesity can be distinguished from rare forms of monogenic obesity, such as leptin deficiency, in which the obesity is often accompanied by characteristic behavioural, developmental and endocrine disorders; from syndromic obesity, such as Prader-Willi syndrome (PWS), in which chromosomal abnormalities result in obesity, developmental abnormalities and other distinct phenotypic features; and from endocrine disorders, such as Cushing’s syndrome, in which obesity is secondary to the primary disorder. Common obesity is postulated to result from a complex genes–environment interaction [2]. It is thought that excessive adipose mass is directly related to an accumulation of surplus energy due to an imbalance between energy intake from the diet and energy output in the form of physical activity. The energy excess is thought to occur when a thrifty genotype is combined with the environment typical of the modern urban-industrial society, in which there is food abundance combined with a low demand for physical activity. The thrifty genotype hypothesis, first put forward by Neel in 1962, is that a highly efficient metabolism evolved under the pressure of a negative energy environment [3]. In the context of an environment with an energy surfeit – the so-called “obesogenic” environment – weight gain is facilitated and obesity is an inevitable consequence. A weakness of this hypothesis is that, whilst the obesogenic environment can explain the geographical distribution and the secular trends in the prevalence of obesity, it cannot account for the variance in BMI between individuals in the same environment; and whilst genetic variation can explain the differences between individuals in the same environment, it cannot explain the secular trends or the initiation of weight gain at a particular point in the life course of the individual. Evidence for the energy surfeit of the environment as a cause of obesity is weak [4], [5], [6] and, despite progress made in identifying quantitative trait loci associated with obesity, genetic disorders of energy balance appear to be rare [7]. In addition, the failure of weight loss intervention, which attempts to reverse the environmental effects, to achieve enduring weight loss, suggests the existence of an unrecognised aetiological factor which interacts between the thrifty genotype and the obesogenic environment. The hypothesis presented herein is that vitamin D deficiency is the cause of obesity and that obesity can be reversed by improving vitamin D status. In outline, it is proposed that common obesity results from an anomalous adaptation to a cold climate which is induced by a fall in vitamin D. A pivotal assumption is that vitamin D originated as a photoreceptor system in primitive organisms, and although it subsequently evolved into a regulator of differentiation, it retained its original role as an ultraviolet (UV)-B radiation-sensitive sensor which serves to signal changes in sunlight intensity. A fall in UV radiation in the autumn is proposed to be the environmental cue for an acclimatory or adaptive response which enhances winter endurance. The winter response entails an increase in body size by the accumulation of fat mass (obesity), which reduces heat conductance to the environment; and the induction of a winter metabolism (the metabolic syndrome), which increases thermogenic capacity. It follows that the production of vitamin D inhibits this response and it may be possible to prevent and treat obesity and the metabolic syndrome by improving vitamin D status. Common obesity has become prevalent in recent decades because of a lack of vitamin D in the urban-industrial environment which is a constructed tropical microclimate created by means of artificial sources of visible radiation (light) and infra-red radiation (heat), but not UV radiation. Endogenous production of vitamin D is redundant in organisms that can obtain sufficient vitamin D from the diet. This dietary supply has enabled organisms to occupy habitats without daily sunlight. Conversely, dietary supply is not required in organisms that have unlimited exposure to sunlight. In the modern urban-industrial environment, both the dietary supply and sunlight exposure have become inadequate to maintain a healthy vitamin D status in the majority of the human population. In the following section the evidence for the main assumptions of the hypothesis is presented in a step-by-step manner. These assumptions challenge the phenomenological approach which dominates the study of obesity. The cause of the increase in the prevalence of obesity and the implications of the hypothesis are examined in the discussion section.
Section snippets
Weight gain is a controlled physiological process
Body-weight is normally stable, even in obesity in which a period of weight gain is often followed by a period of weight stability [8]. It is conceivable that in the normal state, maintenance of a steady body-weight should persist throughout adulthood, controlled by a self-regulating loop since, in common with other physiological systems, homeostastic mechanisms exist for the regulation of weight by the regulation of energy balance [8], [9]. Recent research has identified multiple signals and
The effect of vitamin D status on weight loss
If the model described herein is correct, successful and healthy weight loss should require an increase in vitamin D status. Once an optimal concentration of circulating calcidiol is reached, 25-hydroxylation is reduced and cholecalciferol is deposited in the tissues [60]. This cholecalciferol depot is vital for utilisation during periods of UV-deprivation, or when there is an additional demand for vitamin D, for example during pregnancy and breastfeeding. Since adipose tissue is one of the
References (102)
- et al.
Obesity and mortality: a review of the epidemiological data
Am J Clin Nutr
(1997) - et al.
Obesity and the regulation of energy balance
Cell
(2001) - et al.
Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat
Neuron
(1999) - et al.
Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women
Am J Clin Nutr
(1998) - et al.
Diminished energy requirements in reduced-obese patients
Metabolism
(1984) The metabolic syndrome: Is this diagnosis necessary?
Am J Clin Nutr
(2006)- et al.
Malfunction of vascular control in lifestyle-related diseases: mechanisms underlying endothelial dysfunction in the insulin-resistant state
J Pharmacol Sci
(2004) Overview of general physiologic features and functions of vitamin D
Am J Clin Nutr
(2004)- et al.
Vitamin D compounds in plants
Plant Sci
(2003) - et al.
Provitamins and vitamins D2 and D3 in Cladina spp. over a latitudinal gradient: possible correlation with UV levels
J Photochem Photobiol B
(2001)