Week 10 Lecture 15 2024 PDF

Week 10 Lecture 14 Keto Diet – What’s the evidence?  Keto Diet: Ketogenic Diets reduce the intake of refined sugars and increase proportion of protein and fat to the diet. Purpose is to increase ketogenesis, a product of fatty acid oxidation in the liver. Americans get roughly half thei...

Week 10 Lecture 14 Keto Diet – What’s the evidence?  Keto Diet: Ketogenic Diets reduce the intake of refined sugars and increase proportion of protein and fat to the diet. Purpose is to increase ketogenesis, a product of fatty acid oxidation in the liver. Americans get roughly half their daily calories from carbohydrates, with about 80% of those carb calories coming from added sugars and refined grains — think soda, candies, bagels, pastries and pizza crust. It is known that the Mediterranean diet has important beneficial effects as it is not just a diet but a real lifestyle. Numerous studies have been conducted in recent years to investigate other types of nutritional interventions, such the ketogenic diet (KD) and the very low-calorie ketogenic diet, as medical nutrition therapy for diabetic disease and obesity.  When carbohydrate stores are significantly decreased or fatty acid concentration increases, there is an upregulation of the ketogenic pathway and an increased production of ketone bodies. Ketoacidosis can occur if too many ketone bodies accumulate, such as in cases of uncontrolled diabetes. Activation of adipose tissue lipolysis promotes ketogenesis in the liver by activating the transcription factor PPARalpha. Most organs and tissues can use ketone bodies as an alternative source of energy. The brain uses them as a major source of energy during periods where glucose is not readily available. HMG-CoA reductase is the rate controlling step in cholesterol biosynthesis and the target of Statin drugs. HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled. HMG-CoA reductase is activated by insulin, inhibited by glucagon and oxysterols. Oxysterols are derivatives of cholesterol and accumulate when there is excess cholesterol. When oxysterol levels are high they will also block LDL-receptor mediated endocytosis. When energy levels are low in the cell and [ATP] is decreased, AMPK will be activated and will lead to inhibition of HMG-CoA reductase. HB_GLIC: glycosylated hemoglobin PEP_C: C-Peptide GPT,GOT, GGT: Liver enzymes  PCOS- Polycystic ovary syndrome PCOS is the most common female endocrine disorder in reproductive age, and is characterized by a phenotypic heterogeneity and is associated with a broad spectrum of long-term metabolic and cardio-vascular complications. What exactly causes PCOS is still not clear, but one of the factors that may play an important role in this syndrome seems to be IR. Up to 70% of the patients with PCOS presents IR, and in most cases, this is linked to overweight and obesity. In particular, the typical abdominal distribution of adipose tissue in women with PCOS could actually be considered both a cause and an effect of the disease state in these patients, because if, on the one hand, hyper-androgenism seems to favor an increase of visceral fat, on the other, it seems to represent an important pathogenetic factor in the development and progression of the PCOS in susceptible women. Cincione IR, Graziadio C, Marino F, Vetrani C, Losavio F, Savastano S, Colao A, Laudisio D. Short-time effects of ketogenic diet or modestly hypocaloric Mediterranean diet on overweight and obese women with polycystic ovary syndrome. J Endocrinol Invest. 2022 Nov 19. doi: 10.1007/s40618-022-01943-y. Epub ahead of print. PMID: 36401759. Women who have PCOS may experience: irregular menstrual cycles – menstruation may be less or more frequent due to less frequent ovulation (release of an egg) amenorrhoea (no periods) – some women with PCOS do not menstruate, in some cases for many years excessive facial or body hair growth (or both) acne scalp hair loss reduced fertility (difficulty in becoming pregnant) – related to less frequent or absent ovulation mood changes – including anxiety and depression obesity sleep apnea. Approximately 75% of patients with PCOS are overweight or frankly obese, while central obesity is observed in both normal and in overweight of PCOS patients. Previous studies showed that overweight and/or obesity may be related to metabolic abnormalities in patients with PCOS, such as increased IR and exacerbation of hyper- androgenemia.  The KD is a nutritional protocol characterized by a carbohydrate intake reduced to about 30 g per day or 5% of total energy intake, a high intake of fats and a moderate amount of protein. The reduction of dietary intake of carbohydrates causes a reduction of the amount of blood glucose and therefore also of the concentration of insulin. To date, the evidences for the effects of KD in PCOS are scarce. In a pilot uncontrolled study, the authors have investigated the effect of a very-low-calorie ketogenic diet (VLCKD) in 11 patients with PCOS for 24 weeks. They aimed to investigate the association between PCOS with KD in overweight and/or obese women with PCOS, and evaluate the possible beneficial effects on ovulatory dysfunction, compared to a standard, balanced hypocaloric diet such as Mediterranean diet (MD) This study was carried out in patients with PCOS attending the University Medical Service of Dietetic and Metabolic Diseases of the Faculty of Medicine and Surgery of the University of Foggia, from January 2021 to July 2021. The study was performed in 144 PCOS patients with overweight or obesity. The subjects were enrolled at the outpatient Endocrinology clinic, and included 144 treatment-naïve women that were affected by PCOS attending the Outpatient Clinic of the Unit of Endocrinology in our Department. Thus, a group of 73 patients completed treatment with a KD, and the other group of 71 patients completed treatment with balanced hypocaloric MD. Eligible patients were those with a diagnosis of PCOS classified by the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) diagnosis. This includes the presence of two of the three features of hyper-androgenism (either clinical (hirsutism by elevated Ferriman–Gallwey score)) or biochemical (elevated testosterone or free androgen index), oligomenorrhea (interval between two menstrual periods more than 35 days), or amenorrhea (no vaginal bleeding for at least six months) and the presence of polycystic ovaries on ultrasound scan (≥ 12 follicles measuring 2–9 mm in diameter, or ovarian volume > 10 mL in at least one ovary). The inclusion criteria for all groups were: premenopausal women who were overweight or obese (until BMI 49.9 kg/m2), aged 18–45 years (fertile age), a lack of underlying metabolic disease (type 2 diabetes, hypertension, diagnosed anemia, or any other metabolic disease requiring a special diet). The exclusion criteria for all groups were the following: The exclusion criteria for all groups were the following: Age < 18 years and > 45 years, Menopause (defined as amenorrhea for ≥ 3 years or amenorrhea for ≥ 1 but < 3 years and plasma follicle- stimulating hormone concentrations elevated to the postmenopausal range), Pregnancy or lactation in the past 6 months, Kidney, liver or heart disease, Gout or hyperuricemia, Hyperandrogenism and/or biochemical hyper-androgenemia, oligomenorrhea due to secondary etiologies as per the Endocrine Society Clinical Practice Guidelines and previous publications including endocrine disorders (congenital adrenal hyperplasia, androgen-secreting tumors, Cushing’s syndrome, hyperprolactinaemia, thyroid dysfunction and adrenal disorders) , Pre-existing systemic or psychiatric disease, Use of medications that impact carbohydrate metabolism (oral contraceptive pills, metformin, anti- epileptics, anti-psychotics and glucocorticoids), Specific nutritional regimens or hypocaloric diet in the last three months, Occasional or current of use of drugs that could influence fluid balance, including non-steroidal anti- inflammatory drugs, diuretics, laxative use. Dietary treatment protocol A group of patients with overweight or obesity (n = 73, middle age 33.44 ± 5.68 years, BMI 33.44 ± 5.68 kg/m2) followed a therapy program based on a modified KD protocol defined here as “mixed ketogenic”, with total duration of 45 days. Another group (n = 71, middle age 33.55 ± 4.91 years, BMI 33.55 ± 4.91 kg/m2) followed a therapy program based on a balanced hypocaloric MD. Ketogenic Diet The “mixed ketogenic” diet included a daily protein intake, in part, isolated whey protein powder derived from milk with a high biological value and complete amino acid composition profile with near-zero carbohydrates and fat content, and partly from animal protein sources, such as meat, fish, or eggs. The whey protein powders adopted are isolate milk whey protein enriched with free essential acids and plant protease (Aminexem, Named, Italy). The average nutritional values for two bags of isolate milk whey protein powder enriched with a specific mixture of essential free amino acids contained protein powder 31 gr, carbohydrates 1,2 gr, fats 0,4 gr, essential free amino acid 17,8 g, equivalent to a value of 57% of EAA, where the highest content in EAA found in nature has an EAA of 46–47%, isoleucine 2,69 gr, phenylalanine 0,69 gr, leucine 4,08 gr, lysine 3,58 gr, methionine 0.50 gr, threonine 1,52 gr, tryptophan 0,32 gr, histidine 1,81 gr, leucine isoleucine 4,08 gr, isoleucine 2,69 gr and valine isoleucine 2,58 gr, vitamin D 50, thiamine 1,12 mg, riboflavin 1,4 mg, vitamin B6 1,4 mg, and plant protease, papain 250 mg with enzymatic activity 50.000 TU, tyrosine unit/mg/min, bromelain 250 with enzymatic activity 250 GDU, gelatin digestion unit, for a total of 133 kcal for two bags. A protein intake of 1.1–1.2 g/kg/die ideal body weight was used. The maximum allowable intake of daily carbohydrates was set at 30 g, the total daily caloric intake was established at around 600 kcal; thus, the diet was a very-low-calorie ketogenic diet, this induced a drastic reduction of calories aimed at obtaining weight loss mainly from the FM. The lipid component was set to 30 g/day, mainly consumed in the form of extra virgin olive oil in the amount of 10 g taken during the evening meal, to which the lipid quotas contained in meat and fish and in oil-dried nuts and oilseeds were added. It is essential to highlight that the KD is not balanced from the point of micronutrients, and for this reason, multivitamin and multi-mineral supplements were administered throughout the mixed KD period to avoid nutritional deficiencies. So the nutritional intervention was integrated with a daily multi-mineral multivitamins to avoid deficiencies: one caplet each morning of the multivitamin multi-mineral supplement (Multicentrum, GlaxoSmithKline S.p.A. Verona, Italy) which contains Molybdenum 50 mcg, Magnesium 120 mg, Calcium 200 mg, Phosphorus 105 mg, Zinc 5 mg, Iron 3.75 mg, Iodine 100 mcg, Manganese 2 mg, Potassium 3 mg, Copper 0.5 mg, Chromium 40 mcg, Selenium 30 mcg, Niacin 20 mg (as niacin equivalents), Vitamin A 800 mcg, Folic Acid 200 mcg, Biotin 62,5 mcg, Vitamin C 80 mg, Vitamin E 24 mg (as alpha-tocopherol equivalent), vitamin K 30 mcg, Pantothenic, Acid 7.5 mg, Vitamin B6 2.1 mg, Vitamin B2 2,1 mg, Vitamin B1 1,8 mg, Vitamin D3 10 mcg, Vitamin B12 3 mcg. Moreover, patients were asked to consume no less than 2 L of water/day and take as supplements potassium and magnesium, six tablets per day, for a total of 300 mg of potassium and 113 mg of magnesium (Polase, GlaxoSmithKline S.p.A. Verona, Italy). Mediterranean diet The MD diet was rich in whole grains (pasta, bread, and whole wheat), eggs, poultry, fish, vegetables, legumes, fruits and olive oil as the main condiment, and low in red and processed meat, according to the Mediterranean-style diet pyramid [27,28,29]. The initial assigned energy intake of the MD diet was determined based on the individual’s habitual energy intake evaluated by a nutritional visit by qualified nutritionist during a face-to-face interview, adjusted for body weight and clinical judgment of the nutritionists, to take care of a possible underreporting, common in overweight/obese individuals. The energy distribution of macronutrients was composed of approximately 55% carbohydrates (especially whole wheat), 25% fat (PUFA from olive oil, almonds and pistachios) and 20% protein (especially fish and legumes). The caloric intake was 500 kcal less than the individual daily caloric requirement, and dietary profiles were calculated on the basis of the portion sizes recommended by the Italian Recommended Dietary Allowances. Moreover, all participants were asked to maintain their normal physical activity during the study, although adherence to recommendation was not recorded. Adherence to MD was evaluated by the nutritionist through counseling every 2 weeks and reinforced by phone calls every 2–3 d.