Page 104 - IDF Journal 2023

104
IDF News – Spring 2023
The PronoKal PnK Method for Weight Management
Dr Philip Bazire
PronoKal is a company dedicated to the treatment of overweight and obese patients using a very low-calorie ketogenic diet (VLCKD). We held a webinar with the IDF with the aim of describing the underlying metabolic changes in obesity and how a VLCKD can treat obesity and drastically improve the metabolic and inflammatory environment, favouring effective weight loss and long-term weight stability.
Metabolism and inflammation in obesity
The obesity epidemic continues unabated. In Europe, the UK is one
of the real heavyweights, with obesity approaching 28%. The cost to the health service is estimated to be around £6 billion a year.
Apart from the physical effect of weight, the metabolic changes and associated chronic low-grade inflammation have major negative health consequences: cardiovascular disease and stroke, type 2 diabetes, cancer, neurodegenerative diseases and more.
Healthy adipose tissue is formed of small adipocytes, supporting tissues, and immune cells with a mainly anti- inflammatory phenotype. Weight gain leads to numerous changes, including
• adipocyte distension, triggering inflammatory pathways
• areas of adipose tissue hypoxia which causes cell necrosis, further stimulating inflammation
• obesity-related changes in the gut wall and gut bacteria, allowing antigens
to reach the submucosa and even
the circulation, leading to yet more inflammation
Adipocytes and the pro-inflammatory immune cells accumulating in the adipose tissue secrete pro-inflammatory cytokines, provoking insulin resistance (IR), and inducing inflammatory changes in distant tissues, including the liver, muscle and brain. This is now considered to be the mechanism linking obesity with chronic disease.
IR has a central role in obesity. Insulin
is the energy storage hormone, as it
not only controls glucose uptake and glycogen formation, but also stimulates de novo lipogenesis in the liver and fat storage in adipocytes. At the same time, it inhibits hormone-sensitive lipase (HSL), the rate-limiting enzyme in triglyceride breakdown in the adipocyte lipid droplet. This is important because fatty acids (FAs) must be detached from their glycerol backbone for release into the circulation. This is of particular relevance in the context of ketogenic diets.
Lippincott’s Biochemistry Review (2014) showed how IR elevates blood insulin levels so that basal levels never drop below the threshold for inhibition of
HSL, limiting fat mobilisation. However, increasing IR will eventually reverse this inhibition, leading to increased release of FAs, elevating blood lipids, and further aggravating IR. Additionally, the action on hypothalamic centres increases appetite and the desire for carbohydrate intake and favours fat deposition, especially
in the visceral compartment and as ectopic fat deposits in the liver, pancreas and muscle. This is all in addition to the changes in blood glucose levels.
Weight loss options
Dietary programmes are the least invasive approaches to weight management. However, patients looking for significant weight loss are going to need a major calorie deficit to achieve effective rates of weight loss that will maintain motivation long enough to reach a relevant target
weight. This can be difficult with simple calorie restriction as hunger and intolerance provoke high dropout rates.
Nutritional ketosis is a physiological state induced by a low carbohydrate intake that depletes glycogen stores and forces the body to burn fat. Advantages of ketosis include reduced appetite, increased satiety, mental clarity and a feeling of well- being. This important for patient tolerance of the diet, as they do not feel hungry even when calorie intake is reduced to 600-700 kcal/day, making rapid weight loss possible without the need for drugs or surgery.
Nutritional ketosis does not lead to ketoacidosis. Clinical studies show this mechanism of inducing ketosis is safe, with ketonaemia well below the levels observed in ketoacidosis and with maintenance of normal blood sugar levels and pH. This is because rising ketonaemia stimulates gluconeogenesis, provoking insulin secretion, which promptly reduces the release of FAs from the adipose tissue, reducing ketone body production. Gluconeogenesis also boosts bicarbonate production, which buffers the acidic ketone bodies. The claims of elevation of serum cholesterol and lipid levels with ketogenic diets have been dismissed in a meta-analysis published
in the British Journal of Nutrition (Bezerra Bueno et al. BJN (2013), 110, 1178– 1187).
Pharmaceutical approaches have advanced tremendously in recent
years, but if they are not associated
with individualised dietary and lifestyle modification, then results will be limited in both magnitude and duration, with rapid weight regain on treatment withdrawal. Bariatric surgery is not within the scope of this article.
The PronoKal PnK Method
The PronoKal PnK Method uses a very low-calorie ketogenic diet plus lifestyle modification to achieve rapid weight loss through a loss of fat. Muscle
is maintained by the individualised protein intake, supplementation with 100% of daily requirements of vitamins