Marlena Dudek-Makuch, Pharm. D., Development Expert, Curtis Health Caps
THE EPIDEMIOLOGY OF OBESITY
Obesity is defined as pathological accumulation of the fatty tissue where it accounts for more than 25% of total body mass in women and 20% of body mass in men. The cut-off point is assumed to be if BMI is exceeded by ≥25 kg/m2 (overweight) and 30 kg/m2 (obesity). As regards children, growth charts developed for a given population are taken into consideration. According to available figures, in 2016 even as many as 1.9 billion adults were overweight or obese, accounting for 40% of the global population. In the last 35-40 years, the number of people with BMI ≥30 doubled [1, 2], and the frequency of overweight and obese children even quadrupled . Obesity is becoming an increasingly serious problem also in Poland; already three out of five adults in Poland are overweight, every fourth one is obese and this level is rising constantly . Furthermore, children in Poland are the fastest in Europe to put on weight; more than 18% of eleven- and twelve-year-olds are overweight, and more than 3% are obese [3, 4].
THE INTERRELATION BETWEEN OBESITY AND VITAMIN D LEVEL
Obesity is a risk factor of vitamin D deficiency. Tests held among obese adults and children show that fatty tissue mass is reversely interrelated to the level of 25(OH)D3 in blood serum; every 10% of BMI percentile increase causes a 4.2% drop in 25(OH)D3 concentration.
A considerable deficiency in vitamin D in obese adults is considered to be most probably caused by preferred accumulation of vitamin D in the fatty tissue, which prevents it from being transformed into an active metabolite – calcidiol (25(OH)D3). This hypothesis is confirmed by tests proving that obese people are half less efficient in transforming vitamin D, both taken orally and synthesized in the skin following exposure to sunlight. It has been proven that an increase in vitamin D concentration after exposure toUVB is 57% lower in obese people compared to those with correct body mass. Another probable mechanism of decreased vitamin D concentration in obese people is an increased synthesis of calcitriol (1,25(OH)2D3) – active vitamin D metabolite – in kidneys, which, in the negative feedback mechanism, hinders the production of 25(OH)D3 in liver . Furthermore, excessively overweight people often avoid exposure to sunlight, for fear of being fat-shamed, which causes an insufficient biosynthesis of vitamin D in the skin.
THE IMPACT OF VITAMIN D LEVEL ON DEVELOPING OBESITY
It has also been shown that the relation between the level of vitamin D and obesity is a two-directional one. On the one hand, obesity is related to vitamin D deficiency, while on the other, vitamin D deficiency involves an increased risk of obesity. Vitamin D deficiency raises the level of parathyroid hormone, promoting an inflow of calcium into fatty cells (adipocytes), at the same time increasing lipogenesis, i.e., accumulation and storage of fat in subcutaneous tissue. It has furthermore been demonstrated that a low vitamin D level may cause excess differentiation of preadipocytes into adipocytes, causing the fatty tissue to grow. Epidemiology research available shows that obesity may result from excessive adaptive response in the winter period, and a drop in vitamin D synthesis due to reduced exposure to sunlight results in proneness to increased body mass in cooler periods, while an appropriate concentration thereof in summer months raises the energy expenditure in the fatty tissue, thus preventing obesity .
THE RISK Of METABOLIC DISORDERS IN PEOPLE IN LOW LEVELS OF VITAMIN D AND OVERWEIGHT PEOPLE
An increased amount of the fatty tissue contributes to many metabolic disorders, including not only an impact on carbohydrate and fat management, but also an impact on the hormone system and vitamin D metabolism.
More frequent obesity in children, correlated with a low vitamin D status is accompanied by increased frequency of insulin resistance (IR), impaired glucose tolerance (IGT) and type 2 diabetes (T2D) among children and teenagers. Nearly one third to one half of obese children and young people show clinical symptoms of incorrect glucose metabolism . The most disturbing aspects of a modified glucose metabolism in obese children are the consequences of chronic diseases and premature death as adults . Vitamin D deficiency has been independently related with IR, IGT and T2D; an increasing amount of research shows that there is a need to supplement vitamin D in order to compensate for its deficiency and improve metabolic disorders.
Low concentration of 25(OH)D3 in blood serum may be a risk factor of impaired glucose homeostasis in children. When testing obese children and teenagers in Wisconsin, the concentration of 25(OH)D3 in blood serum was positively related to insulin sensitivity and negatively related to the level of glycated haemoglobin (HbA1c) . Considerable vitamin D deficiency was even observed in children living in lower latitudes in the US (i.e. those with more possibilities of exposure to sunlight) and was negatively related to IR assessment (HOMA-IR [HOmeostatic Model Assessment – Insulin Resistance] and two-hour glucose tolerance test) . Recent analysis of data collected from the national test of 5,867 children and young people (NHANES 01–06) showed that, irrespective of obesity, the concentration of 25(OH)D3 in blood serum was significantly related to several cardiometabolic risk factors, including HOMA-IR and systolic pressure .
Botella-Carretero et al. published the results of their research on the relationship between vitamin D deficiency and obesity they ran on a group of 73 extremely obese people (BMI > 40 kg/m2). Vitamin D deficiency was found in 51% of volunteers, metabolic syndrome in 63%, vitamin D deficiency considerably more frequently applied to obese people with metabolic syndrome (61% vs 33%). Furthermore, patients with diagnosed vitamin D deficiency had their concentration of HDL considerably reduced with increased level of triglycerides .
In a double blind randomized clinical test (RTC) evaluating the effectiveness of vitamin D supplementation in obese teenagers it was proven that 4000 IU of cholecalciferol daily safely increases the concentration of 25(OH)D3 to the level at which an impaired metabolism of glucose and insulin resistance related to obesity is reduced . An observed decrease in insulin resistance was similar to results obtained when metformin was administered, and was independent of changes in body mass. Similarly, in two RCTs with the participation of overweight and IR adults, it was found that supplementing cholecalciferol in doses of 2000 and 4000 IU was necessary to observe clinical improvement in insulin sensitivity [14, 15].
Biological mechanisms used by vitamin D to affect glycaemia control in obesity have not been well explored yet. The proposed mechanisms comprise increased capture of glucose both directly and indirectly, adjusted insulin production through glucose by pancreatic beta cells and reduced inflammation due to obesity .
CONCLUSIONS ON SUPPLEMENTING VITAMIN D IN OBESE PEOPLE
As part of vitamin D deficiency prophylaxis, attention is drawn to the need of increased supplementation thereof in overweight people. Recommended doses for children aged 1 to 18 are 800-1000 IU/day, whereas for adults they range from 2000 to 4000 IU .
It seems, however, that current recommendations take into account vitamin D supplementation in doses appropriate to record the correct growth and mineralization of bones. However, an increasing amount of data shows that vitamin D is a strong hormone activating nuclear receptors of critical importance to the immune system and its correct level reduces the risk of metabolic diseases (type 2 diabetes, insulin resistance, autoimmune diseases).
The results of vitamin D metabolite level test in adults show that people who are not overweight must consume 100 IU to increase the concentration of 25(OH)2D in blood serum by 1.0 ng/ml , whereas obese people must take a doubled dose to achieve an equivalent effect. RCT with the participation of obese teenagers showed that 4000 IU of vitamin D3 daily caused an average increase of 19.5 ng/ml (which corresponds to 1 ng/ml per each 205 IU taken) .
As vitamin D deficiency is quite common in obese children and adults, recommended supplementation levels should probably be higher, especially in children, as levelling out vitamin D deficiency is of considerable importance when preventing metabolic diseases, including insulin resistance and diabetes.
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20 years of experience in phytochemical and biological research, as well as scientific information (assistant professor at the Chair and Institute of Pharmacognosy of the Medical University in Poznań). Author of experimental works and works supported with research examples in the field of isolation and identification of plant-based compounds and evaluation of their biological activity. Lecturer at “Herbs in practice and therapy” post-graduate studies since 2015.
Currently employed at CHC in the R&D Section, Regulatory Department. Responsible, in particular, for drawing up Expert reports (clinical and non-clinical) for medicinal products, clinical report for Rx switch to OTC drugs, clinical evaluation for medicinal products and activity in the field of supervision over the safety of medicinal products, as well as for evaluating the safety of plant-based materials used in medicinal products, medical devices and dietary supplements.
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