Metabolic Health Panel

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1 Metabolic Health Panel

2 Dear Mr. James Galwin, Your sample has arrived for analysis in our laboratory and has been evaluated according to the latest scientific findings and the highest standards in laboratory quality. The analysis of your data was subsequently assessed by our staff members and authorized by our head of laboratory. With this, we submit to you your personal report which we generated for you individually. We thank you for your trust and would be happy to hear your questions and suggestions in order to continuously improve our services. We hope that the analysis fulfills your expectations. Best regards, Your HealthBioCare Team 1

3 Index Basic Principles: Nutrigenomics: DNA and Nutrition What are genes and how are they regulated? What is personalized nutrition? The Metabolic Health Panel: Metabolic Typing Genetic Markers: Single-Nucleotide Polymorphisms Epigenetic Markers: Methylation and Micro-RNA Your Results: Overview of All Gene Variants/SNPs Nutrition and Lifestyle (According to Your Survey Data) Genotyping (Single-Nucleotide Polymorphisms) Your Metabolic Type Your Genetic Risks Nutricosmetics Epigenotyping (Methylation und MicroRNA) Overall Methylation Inflammatory Response Your Prognosis for Weight Loss and Weight Maintenance Epigenetic Status of Your Metabolic Regulation Summary of Your Analysis Results General Information and Recommendations 2

4 Basic Principles: DNA and Nutrition What are genes and how are they regulated? Our genetic information is saved in chromosomes. Chromosomes are comprised of a double-strand DNA which is coiled around histone proteins and located in the nucleus of the cell. DNA, the genetic code, consists of four different nucleotides which are the main building blocks of DNA (A, G, C, and T). These building blocks repeat billions of times in a specific sequence. Genes are sections of DNA where the blueprint for proteins is located. They are read in the cell nucleus. Based on this information, the corresponding protein is then formed. Digestive enzymes as well as muscle tissue are built from these proteins. Small deviations in the sequence of these main building blocks within a gene can affect the function of the protein. One type of genetic variation is called an SNP which is short for single-nucleotide polymorphism. SNPs represent about 90% of all genetic variations in the human genome and are either inherited or are randomly formed. Each is individually distinct and remain for life. SNPs are important in terms of health as they can affect many areas such as metabolism as well as increase or reduce the risk of certain diseases. 3

5 Epigenetics accounts for the mechanisms of gene regulation that can be influenced by environmental factors, diet, and lifestyle. One of the most important mechanisms of gene regulation is DNA methylation. This is a process by which genes can be switched on and off. The activity of genes can thereby be strengthened or weakened. An example of this is the degree to which an enzyme is built. Epigenetic modifications like the methylation in regulatory regions of the genes can change over the course of one s life. External factors such as the environment as well as internal influences such as the specificities of one s diet greatly affect the rate of influence of methylation on metabolism and many other areas of our bodies. With a change in one s lifestyle (diet, exercise, and stress levels), gene activity can not only be actively changed but also acquired. What is personalized nutrition? The research field of nutrigenomics, which is concerned with the interaction between genes and nutrition, has been a focus of modern nutritional science in an effort to create and secure long-term individual nutrition recommendations. We all carry unique gene expressions which influence the functions of metabolism. Therefore, we differ strongly in metabolic capacities as individuals. Depending on genetic conditions, there are also be differences in our needs for macronutrients (proteins, fats, carbohydrates) and micronutrients (vitamins, nutrients, trace minerals). It is scientifically proven that being overweight can be inherited up to 70%. People with a higher genetic precondition have more difficulty in maintaining a healthy body weight or in losing weight. Specific gene variants may cause a strong feeling of hunger or low levels of satiation. In this case, the risk increases for one to gain weight in an effort to attain a good balance of energy. The efficacy of exercise related to body weight is also influenced by SNPs. It is possible through modern gene diagnostics to determine your metabolic type on the grounds of your individual genetic characteristics. It is important to consider the genetic and epigenetic aspects collectively. Therefore, measurement of gene regulation is an additional pillar of the Metabolic Health Panel. Your genes are not your destiny. Our diet has a strong influence on our gene regulation (epigenetics). 4

6 Through the combined analysis of genetic and epigenetic markers, we can assess your risk for obesity and diabetes. Your analysis results offer indications such as how easy or how difficult it is to lose weight and attain a stabilized, healthy body weight through calorie reduction, modulation of macronutrient intake, and by incorporating specific types and durations of exercise. This is the basis for your individual nutrition and exercise recommendations. Metabolic Typing By analyzing twenty-three gene variants (SNPs) and various epigenetic markers (three of methylation and two mirnas), we assign you to one of four metabolic types: Carbohydrate Type: It is possible to metabolize carbohydrates well, but there are difficulties in digesting protein and fat. Fat Type: : Fat is metabolized well, and you can achieve a desired weight with the right intake and lipid composition in your diet. Protein-Type: Proteins are digested well, and one can lose weight with protein rich foods. Balanced Type: All three macronutrients (carbohydrates, fats, and proteins) metabolize equally well. In addition to classification into a respective metabolic type, all analyzed SNPs are evaluated individually and contribute to your personalized nutritional recommendations. These recommendations also include information on appropriately corresponding exercise. 5

7 Epigenetic Markers Not only can epigenetic markers be used to detect various diseases early on, but they can also predict weight loss. Interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) are important inflammatory biomarkers. Additionally, those who are overweight and those who are at a healthy weight differ in methylation patterns of these genes. Long interspersed nuclear element 1 (LINE-1) is a marker for BMI, diabetes, insulin resistance, cardiovascular disease, and cancer. Some studies show that the methylation of LINE-1 can predict the risk of the metabolic syndrome before clinical symptoms appear. MiRNAs are short RNA segments of nineteen to twenty-four nucleotides and have a variety of regulatory tasks in the body. The body s cells specifically target mirnas, which can be used as biomarkers for certain diseases, for metabolic processes, and as signal molecules in cell-to-cell communication. 6

8 All analysed SNPs at a glance Gene FTO (Fat mass and obesity associated gene) MC4R (Melanocortin 4 Receptor) TCF7L2 (Transcription factor 7-like 2) PPARG2 (Peroxisome proliferator activated receptor gamma 2) FADS1 (Fatty acid desaturase) IL-6 (Interleukin 6) Your Variant Significance A/G A polymorphism in this gene is related to obesity. Research shows that carriers of the variants have a BMI that is 0.4 kg / m² / allele higher. Appetite, satiety and eating behavior are affected. T/T This gene regulates energy balance via the hypothalamus and is related to obesity. It is also involved with the leptin system which influences food intake. A SNP increases BMI by 0.25 kg/m²/allele. C/C TCF7L2 is a key component in blood sugar levels. The rarer Tallele causes an increase in TCF7L2 expression, reduces insulin secretion, and is therefore responsible for a higher risk to develop diabetes. People with this genetic variation can counteract this effect by reducing fat and increasing fiber in their diet. C/G This gene is closely related to the development of obesity, heightened fat reserves, and insulin sensitivity. Studies show that in this SNP, an increase in carbohydrate intake can lead to obesity. C/T FADS1 is in the enzyme family involved in ω-3 und ω-6 lipid metabolism, as it results in a double bond to form eicosapentaenoic and arachidonic acids. Carriers of this gene variation usually have elevated levels of triglyceride and low levels of HDL (good cholesterol). There is also an increased risk for coronary heart disease, therefore one should strongly avoid high fat intake. G/G This gene encodes a cytokine that is involved in inflammatory processes and immune stimulation. Carriers of the risk allele have a larger waist circumference and a higher risk for obesity. 7

9 Gene Your Variant Significance A/A This gene plays an important role in the availability of tryptophan. This neurotransmitter is needed for the production of the happiness hormone, serotonin, which in turn affects appetite and mood. A/A Variations in this gene lead to a decrease in the leptin signal which subdues the positive effects of leptin such as satiation and energy expenditure. ADRB3 (Adrenergic receptor B3) A/A This gene is involved in fat metabolism. This gene variation comes with excess fat accumulation, therefore attention should be focused on fat reduction. TFAP2B (Transcription factor AP2ß) A/A TFAP2B is a gene that is expressed in fatty tissue. In carriers of this SNP, a high intake of fat is more effective in achieving weight loss than a low-carb diet. SLC6A14 (Solute carrier family 6 member 14) LEPR (Leptin receptor) ACE (Angiotensin-converting enzyme) UCP1 (Uncoupling Protein 1) APOA5 (Apolipoprotein A5) PLIN (Perilipin) C/C This effects the renin angiotensin aldosterone system (RAAS) which converts angiotensin I to angiotensin II (vasoconstrictive) and deactivates bradykinin (vasodilative) in those with high ACE activity. This is beneficial for the genotype DD in weightlifting but not for genotype II which is related to endurance sports. A/A This thermogenin appears in the mitochondria of brown adipose tissue and is responsible for the production of warmth generated by tremors. USP1 is associated with obesity and diabetes. A/A The gene codes apolipoprotein which is expressed in the liver and is important for triglycerid metabolism. Studies have shown that carriers of this variant can lose weight more easily with a high-fat diet. C/C PLIN is important for the development and the controlled reduction of fat reserves in the body. 8

10 Gene LPL (Lipoproteinlipase) ACTN3 (Alpha-actinin 3) MTHFR (Methyltetrahydrofolatreduktase) CG (Vitamin-D-binding Protein) Your Variant LPL is an enzyme which cleaves triglycerides. SNP carriers show lower triglyceride levels despite an increased fat intake. G/G T/T This gene connects structural proteins of the muscle fibers. Mutations of the gene result in shortened fibers. Non-carriers of the mutation possess fast twist muscle fibers, while mutation carriers are better suited for endurance sports. G/A MTHFR is necessary for the regeneration of methionine from homocysteine. Methionine is an essential amino acid and is important for various processes in the body. A genetic mutation causes a reduction in the enzymatic activity of the MTHFR, resulting in an increased need for folate and B vitamin. G/T SOD2 (Superoxide dismutase 2) A/G AQPR (Aquaporin) NADPH (Nicotinamide-AdenineDinucleotide-Phosphate) MMP1 (Matrix metalloproteinase-1) Significance C/T CG is the main carrier of vitamin D3. With this SNP, the concentration of protein is reduced and, thus, so is that of the vitamin. There are many radicals in the body which must be detoxified by complex methods. In people with this genetic variation, radicals have a longer duration of stay in the body, which is why it is even more important to have a healthy diet rich in antioxidants. AQPRs are proteins which serve to transport water through the cell membrane. This path is impaired in SNP carriers who are then prone to have dry skin. This is a coenzyme which is involved in the numerous redox reactions of the metabolism of the cell. G/G T/G MMP1 is an enzyme which is a part of collagenase. An additional G allele in certain individuals provides a protective effect on the breakdown of collagen. 9

11 Name Date of Birth Analysis Number Date James Galwin Analyzed Parameters Nutrition Lifestyle Genotyping Metabolic Type Excercise Type Health Risks Nutritional and Metabolic Factors Nutricosmetics Epigenotyping (Methylation and MicroRNA) Overall Methylation (DNA stability) Inflammatory Response Your Prognosis for Weight Loss and Stabilization Your Epigenetic Status of Metabolic Regulation 10

12 Evaluation of Your Nutrition and Lifestyle Survey Nutrition Fruits and Vegetables Dairy Products Fish Meats and Cured Meats Whole Grains Fluids Your diet has been compared with the WHO-based recommendations. The results of each food group are shown using a traffic light system. Sweets Your diet is not balanced. Reduce your meat intake to under six portions per week. Furthermore, increase your fiber intake, for example by consuming more whole grains. Lifestyle BMI Nutritional Balance Exercise Susceptibility to Infection Smoking Stress Your lifestyle is a little unbalanced. Try to integrate more exercise into your daily life. 11

13 Genotyping Results 12

14 The analysis of your gene variations indicates that your metabolic health type is suited the most likely to: Balanced. Your Results in Detail Gene Your Genotype Effects on the Metabolism Nutritional Recommendations TCF7L2 Wildtype Regulation of insulin secretion; No increased risk for increased fasting blood sugar levels or for developing Fat-rich foods do not cause you any health problems. diabetes ARDB3 Wildtype Regulation of fat accumulation and lipolysis rate (fat loss); In your case, fat is not excessively stored, however pay attention to your energy balance and to the quality of the fats you eat. MC4R Wildtype Involved in the regulation of energy balance and appetite; Frustration/stress eating No Tendency for frustration/stress eating; Even so, try to snack less often. Incorporate foods that can increase your metabolic rate and support satiation: High fiber intake, high protein intake, green tea, chili, and ginger. Nutritional supplement: glucomannan FTOrs99 Heterozygot Involved in energy homeostasis and body temperature; Neuroendocrine regulation of appetite, hunger, and satiation; Energy consumption while at rest and during exercise; Slight tendency to be overweight due to reduced satiation and simultaneously slightly reduced metabolic rate. Moderately increased risk for positive energy balance and weight gain. PPARG2 Heterozygot Regulates fat storage and insulin sensitivity; Tendency Follow your recommendations for carbohydrate intake. to be overweight when carbs account for >49 E% of You are prone to increased fat storage with a high intake your diet; Exercise yields better results of carbs. 13

15 Gene Your Genotype ApoA5 Wildtype Regulates apolipoprotein which is essential for triglyceride metabolism Keep with the fat intake recommendations of your metabolic type. TFAP2B Wildtype Expressed in adipose tissue; Fat to carbohydrate ratio No impact. Keep with the nutritional recommendations of your metabolic type. LPL Wildtype Enzymes cleave triglycerides Follow the recommendations of your metabolic type. Pay careful attention to your fat intake. Effects on the Metabolism Nutritional Recommendations 14

16 Balanced Type Those with a balanced metabolism can keep with the recommendations of the DACHguidelines. We recommend a diet that is based on the general regulations. The distribution of macronutrients is as following: carbohydrates and fiber should make up the majority of your diet with at least 50 %, fats should make up %, and proteins should be %. However, make sure to prioritize quality over quantity. Try to gradually eliminate simple carbohydrates and instead consume more complex carbohydrates. Fats 25% Proteins 25% Carbohydrates 50% These provide your body all the essential vitamins and minerals that are lost in processed flour when the outermost shell of the grain is removed. Also increase your intake in fruits and vegetables. They also contain complex carbohydrates, provide important nutrients and are a good source of energy for your gut bacteria, which keeps your metabolism in balance. 15

17 Example: A healthy man who weighs 80 kg and who has a PAL (physical activity level) of 1.4 (nearly exclusively sedentary activity, with little leisure activities) has an energy supply of calories (kcal). Of these, carbohydrates should account for 1265 kcal = 308 g, fats (of which are 2.5 % ω-6 and 0.5 % ω-3 FA) should be 690 kcal = 76 g, and 354 kcal = 86 g of protein. To achieve weight loss, a reduction of 500 kcal is recommended, but the amount of protein should not be further reduced. Examples of food groups which are well tolerated: Every vegetable, potatoes, every fruit, avocado, olives, plantbased oils, soy products, common fish (mackerel, salmon, herring, etc.), fermented cow s milk products, sheep s and goat s milk products, traditional grains, rice, rye bread, buckwheat, oats, quinoa, amaranth, nuts, seeds, seedlings, sprouts, eggs, mushrooms, legumes (beans, etc.), meat (game meat and poultry), salad 16

18 Quality of Carbohydrates Glycemic Index and Glycemic Load The speed and strength of our blood sugar increases depending on the type of carbohydrates involved, among other things. Different foods such as whole grain bread or white bread affect the body s blood sugar reactions in different ways. What is the glycemic index? The glycemic index (IG) is a measurement for the rise of blood sugar after an intake of foods that contain carbohydrates. A good comparison is the increasing effect glucose has on blood sugar levels. Glucose is processed fastest in the blood and is assigned as a value of 100. A glycemic index of 60 means that the rise in blood sugar levels triggered by consuming food is only slightly more than half as strong as that of glucose. The value always refers to 50 grams of carbohydrates in the food. What is glycemic load? The glycemic load (GL) not only includes the type of carbohydrate but also takes into account the amount of carbohydrates per serving of food. It refers to a total of 100 grams of food. Vegetables such as carrots, artichokes, asparagus, and tomatoes have a low GL. Foods such as baguettes, bread rolls, and pasta have a high GL. The glycemic load (GL) can be used as a guide to assess the quality of carbohydrate-rich foods. The body s blood sugar levels and insulin response, however, are highly dependent on the composition of your microbiota (bacterial communities in the gut), so this new scientific measurement can be used only as a guideline. The consumption of foods with lower GL, such as whole wheat bread with full grains, whole grain pasta and rice, legumes, and fresh fruit is beneficial. Proteins and fats must not necessarily be avoided if in this category. Glycemic Index Glycemic Load Up to 55 is low Up to 10 is low is mid-range is mid-range 70 and above is high 20 and above is high Calculation of GL: Glycemic index x grams carbohydrates per portion of food/100 = glycemic load 17

19 Quality of Fat: The essential fatty acids linoleic acid and alpha-linolenic acid are very important. These cannot be produced by the body and should therefore be absorbed from foods in our diet, as they also produce substances, such as prostaglandins, which are important for the immune system. Prostaglandins are transmitters in our body which determine blood pressure, blood clotting, salt and water balance, and even the tendency towards inflammation among other things. We need prostaglandins which encourage inflammation so that we can fight infection. Furthermore, we also need prostaglandins which can slow down inflammation. We must have a reasonable balance of both, and both types of prostaglandins are determined by the composition of fatty acids in our diet: Metabolic pathway of essential fatty acids The fatty acids linoleic acid and arachidonic acid belong to the group of omega-6 fatty acids. Alpha-linolenic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) belong to the omega-3 fatty acids. Too much linoleic acid and arachidonic acid along with simultaneous low levels of omega-3 fatty acids (ALA, DHA, and EPA) cause an imbalanced ratio between omega-3 and omega-6 fatty acids. This imbalance causes inflammatory diseases. This means, that the consumption of less omega-6 and more omega-3 fatty acids has beneficial effects. High Amounts of Linoleic Acid Found In: Sunflower oil 65 % Thistle oil 75 % Corn germ oil 59 % Grapeseed oil 71 % Sesame oil 45 % Alpha-linolenic acid nevertheless has a serious limitation: It must first be converted into EPA and DHA by the enzyme FADS1. This enables the production of the anti-inflammatory prostaglandins. If you have a mutation of the gene FADS1 (which is responsible for this conversion), it is advised to supplement your diet with fish oil capsules. Most fish oil capsules contain 500 mg of fish oil and about 150 mg of pure omega-3 fatty acids. You must take six capsules to get about one gram of omega-3 fatty acids. This is the absolute lowest limit to achieve therapeutic benefits of omega-3 fatty acid. To achieve an anti-inflammatory diet, you should shift the balance between omega-3 and omega-6 fatty acids in favor of omega-3 fatty acids. The ratio should be 1:1 to 1:3 in order to curb inflammation. To achieve this: Eat a portion of fatty fish at least two to three times a week. Take one to two tablespoons of linseed oil each day (add in a soup, salad dressing, dips, etc.). Alternatively, you can use hemp oil. Do not cook with linseed or hemp oil. Cook at high temperatures with coconut oil. Olive oil can also be used when you wish. Omega-3 Fatty Acid Content in 100 g of Different Fish: Herring 2040 mg Tuna 1380 mg Salmon 750 mg Mackerel 630 mg Eel 260 mg Trout 140 mg Other Low Fat Fish <100 mg 1 Fish Oil Capsule (1/2 g) 133 mg 18

20 Quality of Protein: What are proteins made of? Proteins are comprised of a variety of amino acids, which are divided into two groups: essential and nonessential. Nonessential amino acids can be formed by the body independently, and in contrast, it is necessary for essential amino acids to be supplied in our diet. The human body requires over twenty-one amino acids. Of these, eight are essential. The standard measurement for evaluating the quality of a protein is referred to as its biological value (BV). This indicates how efficiently a protein from our meal can be converted into an endogenous protein. The key for a high BV is to have a high density of the eight essential amino acids in your diet. The BV will drop if a few of these amino acids are scarce. To set a measure in the evaluation of the BV, chicken egg was assigned as a value of 100. This does not mean that 100% of proteins are converted to body protein, but it is a reference value by which other proteins are measured. On average, animal proteins score better. HOWEVER: Potatoes, soy, and hemp are also three plant-based foods in the top ten of biological value and can be cleverly integrated into your diet. The value of a single protein is limited only by the low content of a single essential amino acid. In the case of grains this would be lysine, tryptophan in corn, and methionine in peas. BV is significantly increased if one supplements with plant-based food that has just this amino acid in excess. In legumes, for example, the amino acid methionine is limited and is thus responsible for a relatively low BV. Corn, millet, amaranth, and rice, however, provide large amounts of methionine and can complement legumes very well to increase BV. Proteins and Insulin Response In terms of the metabolic effect, the impact of insulin from foods is more significant than the impact of blood sugar. In addition to carbohydrates that have a high glycemic index, animal protein is also significantly insulinogenic. The most effective insulin function is achieved mainly by the combination of carbohydrates with a high GI (sugar, white flour) and animal protein from meat and dairy. Plant protein results in a lower insulin response. Insulin as Addictive Substance A resistance to insulin causes the body s cells to become resistant to the effectiveness of insulin to regulate blood sugar levels, though hyperinsulinemia increases other effects of insulin: Insulin has a strong anabolic effect and can promote not only lipid metabolism disorders and obesity, but can also promote the development of cancer. A high intake of animal-based food products in combination with carbohydrates that have a high GI correlates closely with the development of insulin resistance, hyperinsulinemia, obesity, metabolic syndrome, diabetes, type II diabetes mellitus, and cancer. Insulin also increases cholesterol synthesis, sympathetic tones (pulse and elevated blood pressure), and tryptophan levels in the brain which can promote the synthesis of serotonin and melatonin. Losing weight with hyperinsulinemia has a similar effect as overcoming an 19 addiction. In the context of both, healthy aging and cancer prevention, it is therefore necessary to reverse insulin resistance.

21 Proteins and Insulin: The Food Insulin Index The food insulin index (FII) specifies the effects of various foods on insulin levels and considers the function of proteins. The relationship between protein intake and insulin increase is still widely unknown. Insulin is not only important for the absorption of sugar in the cells, but also for the absorption of amino acids. In a similar way to carbohydrates, there are proteins that circulate rapidly and less rapidly in the blood. Animal-based protein from dairy is a fast protein which also triggers a particularly high increase in insulin. Animal-based protein from dairy and meat contains a large amount of glutamine and leucine which trigger high insulin secretion. For example, a steak would be responsible for the release of 27 % more insulin than pasta. Use the food insulin index to compare some foods in relation to 1,000 Kilojoule (kj) Food (1000 kj) Weight (g) Glycemic Index Glycemic Load Food Insulin Index Avocados 112 g Brown Rice 148 g Fish 333 g Fruit Yogurt 260 g Skim Milk 690 ml Mars Bar 54 g Pasta al dente 200 g Pasta with lentils (2000 kj) 27 g Protein, 63 g KH Steak 158 g Steak + Potatoes (2000 kj) 52 g Protein, 40 g KH Tofu Grape Sugar 59 g Walnuts 35 g White Bread 97 g White Beans 281 g

22 Cleverly Combination of Plant-Based Protein As a rule of thumb, if you can combine the following three groups of foods in one meal (even without animal-based protein), you will optimally acquire all the essential amino acids and keep your FII low. (The supplemental effect of protein lasts for four to six hours. It is therefore not mandatory to consume the complementary proteins at every meal.) Combine: Grains, rice, and pseudograins Legumes and soy products (tofu, tempeh, etc.) Nuts and seeds In the case that one of the three in the groups is missing, you can upgrade your plate with potatoes (or sweet potatoes) and plenty of vegetables. Vegetables provide valuable amino acids, although not in such a high quantity as the mentioned food groups. The following list provides examples of how to put this theory into practice with sample dishes: Whole grain pasta with lentil bolognese and cashew parmesan Peas in rice with cashew parmesan Vegetable curry (use almond cream instead of coconut milk) with tofu and brown rice Kitchari (mung beans and basmati rice) with gomasio (sesame salt) Chili sin carne (corn and/or beans) with spelt seitan Lentil dahl (with almond milk) with rice, etc. 21

23 Influence of Genes on Movement and Exercise Genetics and Exercise: Which Exercise Type Are You? Some are successful with endurance sports while others are better suited to and will gain greater health benefits from strength training or a combination of both. By assessing the variations of the gene ACE and ACTN3, we are able to assign you to different exercise types. Through a specific variation in the gene FTO, we can evaluate, how physical movement effects your body weight. An alteration (SNP) in the ACE gene leads to a decrease in gene activity. ACE is part of the bradykinin-aldosterone system. Less activity results in a reduced conversion rate of angiotensin I to angiotensin II, which functions as a vasoconstrictor and narrows the blood vessels. When bradykinin increases in the body, the blood vessels widen, and more oxygen-rich blood is delivered to working muscles. This genotype is advantageous for endurance sports since oxygen-rich blood enables the muscles to work more efficiently and for a longer amount of time. The ACE gene is active in those with the wild type genotype in the ACE gene, and therefore those in this group will benefit from strength training. 22

24 We can also draw conclusions about your exercise type by analyzing the gene ACTN3. Human muscle tissue is sorted into two categories. Slow-twitch (red) muscle fibers are heavily supplied with blood. This optimal oxygen supply has a positive effect in endurance sports, however these slow-twitch fibers are indeed slow and do not generate a lot of power, therefore fast and powerful movements are limited. On the contrary, fast-twitch (white) muscle fibers have less oxygen and tire sooner. They can, react quicker and more forcefully, rendering these fibers capable of fast and powerful movement. The gene ACTN3 is generally active in white muscle tissue. With the SNP in this gene, functions of the white muscle tissues decrease and so does the capability for fast movements. Carriers of this variant benefit more from endurance sports and less from power and sprint training. General Benefits of Physical Exercise: Physical activity is an important protective factor in the prevention of a variety of diseases and obesity. Regular exercise contributes to a balanced energy level as it results in the additional consumption of energy. In addition, it promotes the release of hormones, of which some can lower blood-sugar levels. Muscles absorb from the blood the majority of glucose and fat in our diet and keep blood-sugar and triglyceride levels in balance. HDL cholesterol is cardio-protective and is enhanced by exercise. In this way, one can adhere to a personalized diet and exercise plan to prevent diabetes and other common diseases. When we exercise, different happy hormones are released which can prevent and relieve conditions such as depression, chronic pain, osteoporosis, and much more. 23

25 Exercise Type Analysis of Your Gene Variations According to Your Exercise Type in Detail: Exercise Type: Influence of sport on body weight Endurance Gene Your Gene Variation ACE C/C Endurance sports such as jogging, Nordic walking, biking, and swimming ACTN3 T/T Endurance sports such as jogging, Nordic walking, biking, and swimming Physical Activity The results of your analysis for the ACE and ACTN3 genes reveal that regular exercise in the form of endurance sports like jogging, Nordic Walking, and swimming is beneficial with your genetic makeup. The reason for this is that less angiotensin converting enzymes (ACE) are active, and thus, more bradykinin is produced which acts as a vasodilator and enables more oxygen-rich blood to reach the muscles. If you are a beginner, start small. Try to start with 30 minutes of fast walk three times a week. The pace can and should be increased gradually. IMPORTANT: In the case that you are severely overweight, it is important to start with light intensity and endurance sports. These are gentler for the joints. After a period of healthy weight loss, one can then change to power training and exercises which correspond to your personal exercise type. 24

26 Genetic Risks: Diabetes, Obesity, Nutritional and Metabolic Factors Diabetes is a metabolic disease caused by an abnormal elevation in bloodsugar levels. In type II diabetes mellitus, the pancreas produces insulin, but not in sufficient quantity. In addition, with this disease, the cells in the body can often be resistant to insulin. This means that insulin can no longer optimally perform the vital task of transporting sugar from the blood into the cell. The sugar then, remains in the blood and can cause damage to nerves and small vessels. Risk factors for developing diabetes are: genetics, obesity with mostly visceral abdominal fat, and a flawed nutrition and lifestyle among other things. Obesity is the result of many factors. First, genetic conditions play an essential roll. Disturbed hunger and satiation systems, as well as cravings, often lead to an increased consumption of calories, which are stored immediately in the body in the form of adipose tissue. Genetic risk can be identified through the analysis of gene variations. Further factors, such as environment (friends, occupation, etc.), lack of exercise, and a poor diet can cause weight gain. Unfortunately, obesity opens the door to a variety of other very serious diseases, such as blood pressure, impaired blood lipids, and in extreme cases, arteriosclerosis, diabetes, and coronary heart disease. In addition, one s wellbeing and social life can also suffer. 25

27 Our analysis informs you about your genetic predisposition for these diseases and helps you to prevent and reduce your risks with proper metabolic diet and exercise. For you, we have examined gene variations which influence body weight, obesity, the yo-yo effect, eating habits, diabetes, dyslipidaemia (blood lipids), ω-3 und ω-6 fatty acid metabolism, HDL-cholesterol, oxidative stress, and salt sensitivity. Analysis of Your Gene Variations in Detail: Disturbed Hunger/Satiation Snacking Ravenous Hunger Difficulty in Losing Weight Difficulty in Maintaining Weight Your results show that you have no or very little gene variants that affect your eating habits. That means that from a genetic point of view, you are likely to have balanced eating behavior. Nevertheless, having a sweet tooth, craving processed foods, or snacking often are behaviors that can be created out of habit. Therefore, when you experience a hunger attack, try these tips: drink water, chew gum, snack on nuts, or opt for a piece of fruit or a vegetable. These tips will help you wean your boy off of sweet and/or greasy foods. 26

28 Diabetes Risk Obesity Risk The combination of more genes can predict your genetic risk for diabetes and obesity. Your analysis shows that you have just a low predisposition. Nevertheless, try to integrate a lot of exercise and a healthy lifestyle into your everyday routine. Vitamin Intake Vitamin D Folate and Vitamin B Polymorphisms in our genes suggest an additional need for vitamin D, folate, and/or vitamin B. Take care to include an increased intake of these vitamins in your diet. Sources of vitamin D include the sun (exercise in the fresh air), dairy products, fish, eggs, and mushrooms. Sources of folate and vitamin B are leafy green vegetables, legumes, traditional grains, and animal products 27

29 ω-3 and ω-6 Conversion Carriers of FADS1 SNPs unfortunately have difficulty with forming fatty acids out of ω3 and ω-6 fatty acids. For you, it is advised to supplement your diet with fish oil capsules or a vegetarian alternative in order to provide important substances like eicosapentaenoic acid and docosahesaenoic acid. Blood Lipids Sensitivity to Salt Your analysis shows that you have no genetic predisposition to have a disturbed balance in blood lipids. However, if you still have high cholesterol, high LDL levels, and low HDL, it is most likely diet-related. Pay attention to the types of fats you consume. Reduce consumption of products with processed fat since they contain many saturated and trans fats and raise the risk for disease later on. Consume fats from plant-based sources such as olive oil, avocados, nuts, and healthy fats from animal products such as white meat and fish. These have less cholesterol and contain w-3/w-6 fatty acids. An increase in vegetable consumption helps to reduce LDL and increases HDL. 28

30 List of Genes and Gene Variants Used to Calculate Individual Risks Gene Your Genotype Meaning: IL-6 G/G Diabetes, blood lipids, Omega-3 and 6 fatty acid metabolism; Obesity, weight loss, weight stabilization, Appetite, hunger and satiation, stress eating TCF7L2 C/C Diabetes, obesity, weight loss ARDB3 A/A Diabetes, weight loss MC4R T/T Diabetes, obesity, weight loss Appetite, hunger and satiation UCP A/A Diabetes, obesity PPAR gamma C/G Diabetes, obesity, appetite, hunger and satiation FTO A/G Obesity, appetite, hunger and satiation SLC6A14 A/A Obesity, appetite, hunger and satiation, stress eating TFAB2P A/A Obesity LEPR A/A Weight loss, appetite, hunger and satiation; Weight stabilization PLIN C/C Weight loss FADS1 C/T Omega-3 and 6 fatty acid metabolism APOA5 A/A Blood lipids, weight loss LPL G/G HDL metabolism, blood lipids MTHFR G/A Genomic DNA methylation (increased amounts of genes which are turned off), elevated homocysteine levels; Formation and repair of DNA GC G/T Immune system, bone formation ACE C/C Salt sensitivity 29

31 Nutricosmetics Blemishes on the skin, wrinkles, dryness, and elasticity are complex processes which are 60% reliant on genetics while your lifestyle and environmental factors account for the remaining 40%. Our goal is to provide you with individualized care and individual anti-aging program matched to your skin condition by analyzing the polymorphisms of the genes IL-6, AQPR, MMP1, NADPH and SOD2. Gene Your Genotype Used to assess: IL-6 G/G Skin Elasticity MMP1 Skin Elasticity AquaP T/G C/T Dryness of Skin NADPH G/G Antioxidants SOD2 A/G Antioxidants Skin Elasticity Elasticity is affected mostly by pro-inflammatory processes. Take care to get a sufficient intake of ω-3 and ω-6 fatty acids in your diet. Sources of ω-6-fs are: sunflower oil, safflower oil, maize-germ oil; walnuts as well as meat and liver. Sources for ω-3 are: fish, linseed oil, rapeseed oil, nuts, and chia seeds. The following also provide anti-inflammatory effects: turmeric, ginger, cinnamon, and cayenne. A protein deficiency can also cause the connective tissue to slacken. In this case, focus on fish, lean meat, nuts, legumes, milk, and dairy products. 30

32 Dryness of the Skin Dehydration dries our skin and can lead to a loss of its vitality. Take care to drink at least 2 liters every day. Water or unsweetened tea (green tea is especially beneficial) is the best. Pay also attention to your salt and sugar consumption. Salt is often added to meat and sausage, prepared sauces, and snack foods. Opt for herbs to use as seasoning. Antioxidants Your analysis shows that your detoxification of radicals is in balance. Free radicals attack and damage the cells. Antioxidants in your diet help to catch radicals and to prevent cell damage. To maintain and support your good status, incorporate the following foods into your meal planning: fruits and vegetables which provide valuable antioxidants (vitamin C and E, carotenoids, selenium, zinc, and polyphenols) such as berries, citrus fruits, spinach, apples, broccoli, tomatoes, garlic, grapes, nuts, legumes, and green tea. 31

33 Epigenetic Analysis 32

34 Methylation Gene regulation is influenced by DNA methylation among other things. The binding of a small molecule in the methylation group on DNA can turn genes on and off. These epigenetic markers also work as predictive biomarkers for weight loss. They can help to explain and predict individual differences in weight loss following energy (kcal) restriction. For example, this is shown in the fact that those who are overweight and those at a healthy weight show differences in their methylation patterns. We measure the methylation rate at specific sites in your genome and use this information to calculate your personal prognosis for weight loss. We also evaluate your health status graphically with the traffic light system. DNA Stability Met. Line-1 LINE-1 refers to the elements of the human genome which are not statically fixed but can change location in the genome. In regard to medicine, the LINE-1 family is of great importance, since some diseases are caused by the activation or inactivation of genes by the LINE-1 element. Those with a higher LINE-1 methylation (green areas) respond well to hypocaloric nutrition and have better antioxidant levels. Those who have lower methylation (red areas) should increase calorie deficit with exercise and proper diet. A higher intake of foods rich in antioxidants or a supplement (for instance, TIMEBLOCK inspired by nature) is also advised. Inflammation Met. TNFa TNF-α has a central regulatory role in inflammation and immune responses since it influences immune cells. A high occurrence of TNF-α in adipose tissue leads to the deterioration of insulin signaling and can contribute to the development of insulin resistance and further weight gain. How well one reacts to a reduced calorie diet depends on the methylation rate of these genes. Those who have a less optimal methylation (red bar) need to reduce energy intake in order to reduce body fat. Increasing your energy turnover through daily exercise and also a high intake of low calorie foods is advantageous to those who do not have optimal methylation. 33

35 Combination of Relevant Makers for Weight Reduction Your levels are in the middle range which is a prediction for successful weight reduction. This means that you can expect steady weight loss with an energy deficit of 30% of your total caloric intake. However, to avoid a decrease in energy expenditure while at rest during calorie restriction, you should maintain a fasting window of at least 5 hours between meals. This gives your body a chance to lose fat. Your last meal of the day should be about three hours before you go to bed so that your body can be in optimal hormonal position to lose fat during the night. Intermittent fasting How does it work? The execution of intermittent fasting is conceivably easy. Periods of normal food intake are followed by intervals when you eat nothing. This deliberately sets the body up to be in a state of no-calorie intake with the goal of reducing fat while protecting muscle mass or even expanding muscle mass. The word intermittent means that food intake is only interrupted and that caloric intake must not be restricted for too long. This stabilizes insulin levels, making it easier to lose weight. Various studies have shown that intermittent fasting protects the immune and cardiovascular systems and possibly slows down the aging process. Metabolism and Fasting: Intermittent fasting does not cause a decrease in metabolism though this myth is often attributed to the practice. 34

36 Health Benefits: Potential health benefits were found mainly by studies on animals. These studies indicate: Longer lifespan Lowered risk for type II diabetes Cardio-protective and neuro-protective effects Better brain function in old age Decreased likelihood for cancer There are two basic types of intermittent fasting which can split off into further varieties. 1: A complete day of fasting per week (5:2 method) This variation calls for fasting on one or two days in a week. On days when you eat, take the amount of macronutrients (proteins, carbohydrates, fats) that we have specified based on your genotyping. 2: Daily fasting periods (16/8 method) The numbers 16 and 8 refer to the two timeframes when you fast and eat. A 16-hour fasting interval is followed by an 8-hour meal phase. Within these eight hours, take the amount of macronutrients (proteins, carbohydrates, fats) that we have specified based on your genotyping. The 8-hour calorie intake phase is followed by 16-hours of fasting. What is allowed while fasting Wasser (mind. 2, 5 Liter) Water (at least 2.5 Liters) Coffee (without or with very little milk, a dash of cream, or alternatively unsweetened nut milks) All types of tea (without sugar) Green tea with a dash of lemon is particularly advantageous since it promotes metabolism. Add a dash of lemon juice to water. The lemon deploys alkaline effects in the body. It is important to support the body with alkaline foods especially when fasting and losing weight. Many toxins accumulate in fatty tissue. When fat is broken down, it gets into the bloodstream and must be detoxified. An example of a time table for a 16/8 plan would be: Fast from 7pm to 11am and eat from 11am to 7pm. This timetable can, of course, be flexible according to your everyday life and wishes, but the 16/8 apportionment must be retained. Simply try out how the periodization works for you personally. It is also possible to switch back to a more normal food intake on weekends. 35

37 Your epigenetic Status of microrna Metabolic Regulation: MiRNAs are short RNA fragments of 19 to 24 nucleotides. These non-coding RNAs have diverse regulatory functions in the body. A good third of human genes are regulated by mirnas. They are, so to speak, the fine-tuning of gene regulation. Cells in the body target mirnas which function as signal molecules in the communication between cells. These small signal molecules, therefore, serve as biomarkers for metabolism. We have determined the blood levels of two mirnas which can be positively influenced by lifestyle. Inflammation-, micronutrient-, and BMI-associated mirna This mirna increases proportionally with BMI in the blood. Increased inflammation and poor zinc and folate levels also increase the amount of these markers in the blood. It is important to strive for a normal BMI if you are in the high or medium status (indicated by red or yellow) and to take care to increase zinc and folate intake. Inflammation, Micronutrients, and BMI-Associated mirna Your level for inflammation-, weight-, and micronutrient-related mirna is in the average range. Try to improve this by slightly increasing your daily activity levels, for instance, opting for stairs instead of an elevator, riding your bike to work, talking a walk, etc. Stick with your personal recommendations for exercise and nutrition in order to reach optimal range for this mirna. In this way, you can experience the positive effects of this mirna on weight loss, metabolic health, and healthy aging. Pay special attention to your zinc and folate intake! 36

38 MiRNA and the Formation of Fatty Tissue All humans have white and brown or beige adipose tissue. The latter provides more energy in the form of heat. Certain mirnas influence whether more brown or beige adipose tissue is formed in comparison to white adipose tissue. Brown and beige fat requires more energy which is then released in the form of heat. This increases your basal metabolic rate. A low blood level of these mirnas reduces the negative influence on energy metabolism in FTO-SNP carriers, as more brown or beige adipose tissue is formed from the white. This promotes weight reduction. With regular exercise, the blood level of this mirna can be lowered. MiRNA and the Formation of Adipose Tissue Your levels for this mirna are in the average range. You can positively influence your metabolism by increasing your daily activity. For instance, opt for stairs rather than the elevator, ride your bike to work, or go on a walk. To improve levels of this mirna, stick to the exercise and nutritional recommendations generated personally for you. In this way, you can experience the positive effects of this FTO-gene regulating mirna on weight loss and metabolic rate. 37

39 General Overview Lifestyle: Metabolic Type: BMI Balanced. Nutritional Balance Fats 25% Proteins 25% Exercise Susceptibility to Infection Smoking BMI: 25,1 Stress Exercise Type: Nutrition: Carbohydrates 50% Fruits and Vegetables Endurance Dairy Products Fish Meats and Cured Meats Whole Grains Fluids Sweets Nutricosmetics: Skin Elasticity Dryness of the Skin Antioxidants Methylation: Combination of Relevant Makers for Weight Reduction Met. Line-1 Met. TNFa MiRNA: MiRNA and the Formation of Adipose Tissue Inflammation, Micronutrients, and BMI-Associated mirna 38

40 Risks: Eating Habits: Disturbed Hunger\Satiation Snacking Ravenous Hunger Difficulty in Losing Weight Difficulty in Maintaining Weight Diabetes/Obesity: Diabetes Risk Obesity Risk Vitamins Intake: Vitamin Intake Vitamin D Folate and Vitamin B Omega-3 and Omega-6: ω-3 and ω-6 Conversion Blood Lipids: Blood Lipids Sensitivity to Salt 39

41 Interpretation of Your Nutritional Status 40

42 The basal metabolic rate (calculated with the Harris-Benedict formula) indicates how many calories a person needs per day if that person is in absolute rest. This value is to be understood as a guideline and varies depending on each body. Certain activities require more calories and are not taken into account. These will be accounted for in your daily energy metabolism. BASAL METABOLIC RATE X ENERGY VOLUME = CALORIC NEED Age: 62 Your Basal Metabolic Rate: 1654 Kcal Your Daily Energy Demand: 2548,8 Kcal The evaluation of your epigenetic markers for weight reduction show that successful weight loss can result from a 20 % energy (kcal) deficit. A 20 % kcal deficit of your energy volume of 2548,8 Kcal is 509,6 kcal/day. Target intake of energy per day during weight loss period: ca. 2116,8 Kcal Macro-Nutrients Intake: Proteins 661,6 Kcal Carbohydrates 1323,2 Kcal Fats 661,6 Kcal BMI (Body Mass Index): Age Normal BMI Female Ideal BMI Female Normal BMI Male Ideal BMI Male ,5-23,9 20,75 18,5-24,9 21, ,5-24,9 21,75 19,5-25,9 22, ,5-25,9 22,75 20,5-26,9 23, ,5-26,9 23,75 21,5-27,9 24, ,5-27,9 24,75 22,5-28,9 25,75 Über 64 22,5-28,9 25,75 23,5-29,9 26,75 25,1 41

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