Category Archives: Obesity

Chondroiton Sulfate and Glucosamine is effective in moderate-to-severe knee osteoarthritis.

lo res cartilage structure copy GlucosamineCombined chondroitin sulfate and glucosamine on Knee osteoarthritis

The MOVES trial tested whether chondroitin sulfate (CS)  plus glucosamine hydrochloride (GH) has comparable
efficacy to celecoxib after 6 months of treatment in patients
with painful knee osteoarthritis.

MOVES study for Chondroiton Sulfate and GH  < LINK to study

  • The trial tested 606 patients with moderate-to-severe knee osteoarthritis (OA) based on a WOMAC (Western Ontario and McMaster osteoarthritis index) scale >301 (range is 0-500). Treatment with 400 mg of CS and 500 mg GH three times a day was compared with the effects of Celocoxib 200 mg once a day for 6 months.
  • The results: Both treatments were equally effective. For CS/GH Vs.  Celocoxib, both treatments resulted in decreasing pain by 50% as well as joint swelling.
  • In summary: Using either Celocoxib or GH/CS had equal effect in decreasing joint stiffness, pain, functional limitations, and joint swelling after 6 months in the treatment of OA of the knee.
  • Be certain to obtain your GH/CS from a trusted source which can be checked on line at Consumer Lab  or the US Pharmacopeia.
  • Side effects of Glucosamine may be an increase in glucose levels, so be careful if you are diabetic. Also if you have an allergy to shellfish, Glucosamine can be derived from materials in shellfish, so again be careful.
  • Recommended daily doses of Glucosamine is 1,500 mg ans 1,200 mg of chondroiton.
  •  Glucosamine, Chondroitin Sulfate, and the Two in Combination NEJM  GAIT trial < link to gate trial. A prior study in the New Englandd Journal of Medicine had shown results hinting that CS/GH work best in moderate-to-severe disease, but not so much is lesser OA pain.In the study discussion, it was noted:  Analysis of the prespecified subgroup of patients with moderate-to severe pain demonstrated that combination therapy significantly decreased knee pain related to osteoarthritis, as measured by the primary outcome or by the OMERACT–OARSI response rate. We did not identify significant benefits associated with the use of glucosamine or chondroitin sulfate alone. Although the results for glucosamine did not reach significance, the possibility of a positive  effect in the subgroup of patients with moderate-to-severe pain cannot be excluded, since the difference from placebo in the OMERACT–OARSI response rate approached significance in this group. Treatment with chondroitin sulfate was associated with a significant decrease in the incidence of joint swelling, effusion, or both. We did not find an increased risk of ischemic cardiovascular events among patients who received celecoxib or among patients with diabetes who received glucosamine, but this study was not powered to assess these risks… Our finding is that the combination of glucosamine and chondroitin sulfate may have some efficacy in patients with moderate-to-severe symptoms.
  • Be certain to lose weight and exercise.  Obesity places huge stress on knees and ankles and hips. Supplements should complement these steps.

 

Insane Medicine – Liraglutide (Saxenda) for weight loss!!

  • Liraglutide is a glucagon-like 1 peptide that has been available for diabetes management for a few years and now has an added FDA approval for weight loss management!!
  • There are more options for weight management as of now!
    There are more options for weight management as of now!

    obesity-big

  • To date, Phentermine/topiramate ER (Qsymia) is the most effective drug available. Locaserin (Belviq) is another approved drug for weight loss, but it is less effective.  However, it is better tolerated. Other options such as Xenical are helpful, but it prevents absorption of food and can cause excessive bloating and gas in some patients. Contrave (Wellbutrin and Naltrexone) is also effective but has neuropsychiatric effects.
  • Liraglutide is used to treat type 2 diabetes at a dose of 1.8 mg a day. It is injectable. The weight loss form of the drug is a dose of up to 3.0 mg a day injected. The amount of weight loss varies as the dose approaches the upper limit of 3 mg a day.
  • Liraglutide decreases appetite and therefore energy intake, which is how it causes weight loss. It also delays gastric emptying. Used as an adjunct to physical exercise and dieting, it has resulted in up to an 8 kg body weight loss over the 56 week course of treatment [ −8.0±6.7% (−8.4±7.3 kg)].
  • Liraglutide treatment was associated with reductions in cardiometabolic risk factors, including waist circumference, blood pressure, and inflammatory markers. Fasting lipid profiles were also improved as well. The combination of weight loss and improved glycemic control probably contributed to the observed reductions in the prevalence of prediabetes and the delayed onset of type 2 diabetes.
  • Side effects include an increased incidence of gallstones, which commonly increase with weight loss.  Nausea and constipation (or diarrhea) has been reported. Rarely, pancreatitis and kidney failure has occurred. The FDA has required a boxed warning about the risk of thyroid C-cell tumors in the package insert, and in patient’s with a family history of Multiple Endocrine Neoplasia Type 2 or medullary thyroid carcinoma, this treatment is to be avoided.
  • Treatment is started at 0.6 mg injected a day and increased weekly by another 0.6 mg until a total of 3 mg a day is injected. At 16 weeks, if a 4% body weight loss is not achieved, therapy should be stopped. Total cost per month is about $1000.00!
  • For patients who have a BMI>30 (Body mass index) and are not diabetic, or have a BMI>27 with a risk factor, such as hyperlipidemia or diabetes, Saxenda is a consideration for weight loss.
  • Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems

    Liraglutide has effects on a number of metabolic systems
    Liraglutide has effects on a number of metabolic systems

Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to methylglyoxal stress

A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management

Liraglutide (Saxenda) for Weight Loss

http://ajpgi.physiology.org/content/302/2/G225

Insane Medicine – Akkermansia muciniphila and the Gut biome

  • The bacteria in your gut create a huge ecosystem or biome that has major effects on your overall health. More and more studies are demonstrating this, including the one below.
  • The gut microbiota diversity and function plays a role in the development of obesity and metabolic ailments.
  • Akkermansia muciniphila is a mucin-degrading bacteria found in the mucus layer of the intestine that has been found to help improve your metabolic status by increasing insulin sensitivity and glucose regulation.
  • Obese individuals and those with Type 2 diabetes differ from leaner individuals in the constitution of their gut micobiome and the microbial gene richness. It has been found in mice that higher levels of  mucin-degrading bacteria (Akkermansia muciniphila) are inversely associated with body fat and glucose intolerance. In other words, these bacteria help improve glucose metabolism and improve overall metabolic health.
  • The article below demonstrated that Akkermansia muciniphila, when increased in the gut, resulted in healthier metabolic status in obese people. This was accomplished by caloric restriction, which then resulted in increased microbial gene richness ( a good thing) and improved glucose homeostasis and blood lipids. Following a FODMAP diet also increased Akkermansia muciniphila in the gut.
  • The higher the Akkermansia muciniphila bacteria levels are in the gut, it seems that you will have better glucose metabolism, better waist-to-hip ratios, lower fasting glucose levels, better triglyceride levels,  and better fat distribution.
  • Increasing amounts of fat in the form of fat hypertrophy is a proinflammatory condition and is associated with bad cardiometabolic risk. This inflammatory risk is measured through insulin levels, interleukin-6, lipopolysaccharide levels, and C reactive protein levels in the blood stream. Caloric restriction leads to increased Akkermansia muciniphila and other healthy bacteria, which increases the overall microbial gene richness. These bacteria lower the inflammatory markers through their metabolic activity. This results in better metabolic outcomes.
  • How does this all occur? Akkermansia muciniphila ferments waste products into other items that other beneficial bacteria species can feed on. Short chained fatty acids are one of those items as well as acetate, which becomes an anorectant when absorbed in the body. In other words, you eat less.
  • The key here is that the gut biome plays a tremendous role in our overall health, and caloric restriction results in a  boosting of the healthy richness of our gut biome, which is probably a key part of overall health!

KEY study in GUT :  http://gut.bmj.com/content/early/2015/05/22/gutjnl-2014-308778.full.pdf+html

Akkermansia

 

 

 

http://www.gutmicrobiotaforhealth.com/akkermansia-as-a-target-for-obesity-authors-explained-1496

 

http://www.biotanutrition.com/2015/01/17/akkermansia-muciniphila-a-biomarker-of-healthy-gut/

 

Dao M, Everard A, et al. Akkermansia muciniphilaand improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut.2015. 

Gut Bacteria and Food Allergies:

  • Gut bacteria also seem to play an integral role in other aspects of our health including food allergies. The presence of Clostridia in our gut appears to be protective against food allergies by causing the release of Interleukin-22 from gut cells, thereby decreasing permeability of the gut to allergens, which cause allergic reaction. Without gut permeability, the antigens cannot create an allergic immune response. Food allergies have been increasing in recent times due  to modern dietary and hygienic practices, which disturb our natural gut biome.High fat diets, antibiotics,  and formula feeding have all affected our gut bacteria, some of which protect us against food allergies. In a study, it was shown that germ-free mice and mice treated with antibiotics both reacted to peanuts, however, when clostridia was introduced, the reaction went away! This demonstrates how Clostridia decreases food allergies.  The study, “Commensal bacteria protect against food allergen sensitization,” was the source of this information.
  • Clostridia protects against Food Allergies

Insane Medicine – Even older people should watch their diet

Successful aging requires continued effort for the best outcome. Do you want to live to one hundred and be bed-bound or live to one hundred and be active? Successfully aging people need to consider healthful behaviors to maintain their independence and health. Conditions that affect people over sixty can be modified and lessened by nutritional strategies:

  1. Cardiovascular diseaseHigh blood pressure, cholesterol/triglycerides, and obesity are modifiable by diet and medication. Weight control allows for better mobility, less pain, and fewer heart attacks. Obesity is associated with sleep apnea, as well, which reduces quality of life because it makes you fatigued in the day time and generally weak.
  2. Cerebrovascular Disease: Such as strokes and dementia are impacted by high blood pressure and diet. First off, quit smoking to decrease your risk of dementia and stroke. Decrease your sodium intake to decrease your blood pressure (1500 mg of sodium a day is about right for an average diet.) Use herbs and spices to flavor your foods. Foods such as cold cuts, cheeses, breads, pizza, pasta dishes, snack foods, and soups have higher levels of sodium, so beware. Consider following the DASH diet: http://www.nhlbi.nih.gov/health/health-topics/topics/dash  and http://health.gov/dietaryguidelines/2015-scientific-report/ 
  3. Diabetes Control: Diabetes affects everything from your eyes to your kidneys. There is a four-fold increased risk of death from heart disease or stroke if you are diabetic. Take your medicines, track your hemoglobin A1C (sugar control measure) and eat  food with a low glycemic index. Eat food with less fat and avoid high-sugar content items, but include more vegetables and whole grains to maintain glucose control. It takes a lot of effort if you are diabetic, so don’t let diabetes take your life one leg at a time!
  4. Cancer: Get your recommended screening examinations. Also, maintain a healthy weight since obese people have higher risks of cancer!
  5. Chronic Kidney Disease: Another disease modifiable by diet control – CKD risk is increased if you have hypertension, diabetes, obesity, or cardiovascular disease. A healthy diet and physical activity will maintain your weight and blood pressure, minimizing aging’s impact on your kidneys!

Suggestions:

  • Eat bright colored vegetables (carrots, brocolli) and deep colored fruits (berries) for phytochemical, healthy support.
  • Chose whole, enriched, fortified grains and cereals, i.e. whole wheat bread.
  • Chose low and non-fat dairy products: Yogurt and low-lactose milk
  • Use herbs and spices to add flavors to meals
  • Lots of fluids: no sodas
  • Exercise

Insane Medicine – Dietary Review!

I wanted to generalize some overall health information in this particular blog and incorporate items that are important for increasing successful strategies for aging and maintaining your health.

  • Remember that circulation is important in your body because it provides energy and sustains life in the various tissues. Regular exercise is a way to keep your body maximally conditioned. Your circulation delvers oxygen and nutrients to your body and at the same time allows toxins to be removed as it passes through the liver, kidney, and lymph systems. So be certain to keep moving and exercise to maximize your health.
  • Eat more plant foods. As a result of doing this, you take in less fat and will increase your fiber intake. This allows more protecting antioxidants to be incorporated into your body. Ingesting more fiber allows for better waste removal, and less fat intake results in a decreased tendency for your blood to thicken and clot, thus decreasing cardiovascular risk. The large amount of protecting agents in plant-based diets results in less inflammation in the body and less cellular damage.
  • Choose plant foods with strong flavors and with bright colors. Have a healthy fat focus in your diet. Chose your beverages you drink wisely, in other words, stop drinking sodas! Try your best to allow your stomach to be empty  and have ‘hunger pains’ for at least two thirty minute periods each day.
  • Remember that the body evolved in a world where salt, sugar, and fat were scarce and are like addictive drugs. Be careful to avoid choosing processed foods when possible and not adding salt and sugar to your meals. Avoid sodas ( which are high in sugar content)! Even noncaloric beverages may be increasing our desire for sweet food and spurring increasing rates of obesity.
  • Fructose in our foods has been a source of increasing weight gain in our society. Fructose and glucose (both sugars) have a differential effect on the brain. Glucose will reduce activation of brain regions that are involved in appetite, motivation, and reward and will increase our sense of satiety and decrease our food seeking behavior. Fructose does not do this. It is sweet, but it makes us want more! Corn sweeteners (fructose) have correlated with rising obesity.
  • Plant-based foods give us phytochemicals which act as protectors. Plant-based foods give smell, taste, and fragrance to our diet. They have an antioxidant effect. Kale, cabbage, broccoli, and  arugula have a sulfur based mustard taste that increase detoxification enzymes in the body. You should get 5-9 servings of colorful, flavorful vegetables in your diet each day – five servings for smaller people and at least nine servings if you are a big person. How much is a serving for vegetables? One-half cup cut up is equal to a serving, in general, for vegetables (for raw spinach, a whole cup is equal to a serving)
  • So again – look for colorful vegetables, as they have higher levels of phytochemicals in them, For example, zucchini has a green outside but mostly colorless interior, and therefore is a poorer choice of a vegetable. Instead, go for the carrots, spinach, broccoli, and yellow squash as options, since they have more color to them and therefore more protective phytonutrients! You will find higher levels of Vitamin A in deep orange vegetables such as carrots. The carotenoids and retinol in these vegetables impart the orange coloring and give the protective qualities of these vegetables.  Cruciferous vegetables have a big, strong flavor with sulfur components. They have powerful antioxidants in them and include arugula, broccoli, brussel sprouts, cauliflower, kale, kholorabi, radish, rutabaga, and turnips. Citrus fruits are high in Vitamin C, which helps fight infection. They also have an antihistamine/anti-allergic effect as well as anti-oxidant effect, which protects cell membranes and DNA in the body from oxidative damage. Vitamin C is important in the production of collagen component of connective tissues such as tendons and ligaments.
  • Eating up to nine servings a day of vegetables was associated with 24% less obesity in one study. Why? Because you eat less of other fatty foods.
  • Fiber rich foods  are very important in the diet. Vegetables, fruits, beans, whole grains are all rich sources of protective nutrients and phytochemicals and have a lower glycemic load as well. Eating foods with high fiber content results in less obesity since people who consume high-fiber foods feel more full. Likewise, higher fiber meals cause increase transit through the gut and decrease carcinogen exposure. This results in less colon cancer risk! Soluble fiber decreases cholesterol levels while fibrous food will increase the amount of protective gut bacteria.
  • We will be discussing the gut biome over time in this blog. Your gut has a population of bacteria that live and thrive but also help us maintain homeostasis. Alterations in the gut biome (bacterial population) can result in inflammation and disease. Immune compromise can occur if the gut biome is altered or destroyed. It turns out that soluble fiber is a food source for these necessary gut bacteria to remain healthy, and hence us as well.
  • We need 25 grams of fiber every day. A rule of thumb is one gets 2 grams of fiber per vegetable/fruit serving, so 5 servings of vegetables equals 10 gm of fiber.
  • Whole grains are a good source of fiber. One slice of whole grain bread is equal to a serving. A cup of cooked oatmeal is considered a serving. A thought for increasing fiber content is to use wheat berries, which cook like brown rice. Adding sunflowers to them can make a nutritious bundle.
    Wheat berries cook like brown rice and taste great when mixed with sunflower seeds!
    Wheat berries cook like brown rice and taste great when mixed with sunflower seeds!

    Cooked beans, peas , and lentils have 6 gm of fiber per half-cup of cooked item. They are excellent sources of fiber.

    Consider adding mung beans, which are bean sprouts that cook like lentils, in a dish with some olive oil, salt, and pepper and placing it over pasta.
    Consider adding mung beans, which are bean sprouts that cook like lentils, in a dish with some olive oil, salt, and pepper and placing it over pasta.

     

  • Always be certain that you check to see if a bread item is whole grain. Check the ingredient list. You want whole, sprouted, or malted wheat or whole grain on the label. Beware if it says wheat flour, for that is the same as white flour.
  • Put as many vegetables on your salad as possible. Lettuce has very little fiber.
  • Be certain to take in 5-10 grams a day of soluble fiber out of the 25-35 grams of fiber that is needed. Soluble fiber lowers cholesterol levels and feeds the healthy gut bacteria to support our immune system. An orange (medium) has 3-5 grams of soluble fiber, while a half cup of beans has 3-5 grams. Two tablespoons of ground flaxseed has 1.5 grams of soluble fiber. Flaxseed can be ground into flaxmeal.
  • Of note, a high fiber diet provides a low glycemic load, which is great for diabetics, but particle size of the fiber source is important. For example, old fashioned or scottish oats are best for fiber sources, whereas smaller particle sized grain products lose the fiber benefits. It turns out the glycemic index is higher in small-particles of grains (they get absorbed easier).
  • Higher glycemic-load foods are associated with chronic diseases. As people absorb more carbohydrates and gain weight, their insulin level increases in response, which promotes increased fat storage, thereby leading to the need for more insulin to control blood  sugar. This results in diabetes over time. Also cancer is more common in obese individuals as insulin-like growth factor (IL-GF) drives cancer growth. IL-GF is involved in glucose metabolism. A diet with a low glycemic load would include non-starchy vegetables except potatoes. Whole grains are high in glycemic load and make diabetes more difficult to contol. Pasta, rice, potato, and virus have high glycemic loads and are not as healthy. Fruit has high fiber content and a LOW glycemic index. High fat foods also have lower glycemic load. So aim for foods with lower glycemic indices as they allow for better body sugar control.
  • Fats affect inflammation in the body. High body fat content, especially abdominal fat,  is linked to cancer risk, diabetes, arthritis, Alzheimer’s disease, and autoimmune disorders. In an anti-inflammatory diet, one wants to avoid excess fat.  Decrease your fatty food intake, especially fried foods and fast foods. Decrease your dressings and mayonnaise on your foods. Decrease the amount of sweets in your diet, especially cookies and cake. Eat more fish and seafood (not fried) at least 2-3 times a week, except for farmed salmon, which should be eaten only once a month. Avoid sweetened beverages and limit foods with sweeteners. Eat more vegetables, fruits, whole grains, and beans.
    Beans are good!
    Beans are good!

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    Use extra virgin olive oil to toss in your vegetable or salad to allow easier coating of the leaves with your favorite dressing. By doing that, you will use less dressing and spread it out evenly!
    Use extra virgin olive oil to toss in your vegetable or salad to allow easier coating of the leaves with your favorite dressing. By doing that, you will use less dressing and spread it out evenly! Less dressing=Less fat!

     

  • Fat balance is important in your diet. Avoid the pro inflammatory fats, such as omega-6 polyunsaturated fats (PUFA) such as corn, cottonseed, soy, safflower, and sunflower oils, which are high in omega-6 oils. decrease your meat intake and decrease fish intake that are fed these products such as farm-grown salmon! Omega-3 PUFA are anti-inflammatory. and are present in flaxseed oil. Also, pasture-fed livestock (‘grass-fed’) have less omega-6 fatty acid in them. Avoid livestock that are fed grain or corn at any time, since that increases the amount of proinflammatoy PUFA in them. ‘Grass finished’ livestock means that the livestock ate grass until they are butchered. Choose grass-fed products only!
  • Some fat-health guidelines include avoiding fat soluble contaminants by eating food items lower on the food chain, such as smaller animals (fish) and avoiding farmed salmon. Eat only organic products. Avoid saturated fats, present in processed foods and dairy products or red meat. Avoid rancid fats by limiting aged cheese and meat (deli meat) in your diet. Chose healthy fats, which increase satiety and help absorb fat soluble vitamins. Healthy fats include avocados, olive oil, sardines, nuts, seeds, and olives.  Larger animals have more time to get contaminants in them. Chicken and sardines, which are lower on the food chain, live short lives. low in the food chain, and accumulate less toxins. Don’t eat fats that are solid at room temperature,. Avoid processed foods and meats (deli meats)
  • Rancid fats add oxidative stress to your body.Increase your monounsaturated fat intake such as avocado and olive oil, which are heart-healthy.  It was found that people who eat less saturated fat and more monounsaturated fats in their diet have better cognitive performance and verbal memory over time!
  • Osteoporosis prevention: Increase the following: exercise, calcium intake, vitamin D, protein and potassium . They all help build healthy bones! Protein is needed to build the bony matrix. Avoid caffeine (>300 mg a day) and avoid smoking and excessive sodium intake. Avoid being too thin. These factors all impact bone health in negative ways. Excessive sodium in the diet causes the kidneys to waste calcium in the urine. Be certain to get 1200 mg of calcium a day in the diet. For example, 1 or 2% no-fat milk has 300 mg of calcium per cup, while yogurt has 250 mg in 6 ounces. Please note that not all tofu has enough calcium in it, so check the labels. Also, corn tortillas (traditional mad with lime) has calcium in it ( fiver per day provides a lot of calcium)
  • Calcium bioavailability in the diet depends on the source of the calcium. There is calcium carbonate, calcium citrate, calcium malate, calcium phosphate, calcium gluconate, and calcium lactate. Tums has calcium carbonate in it and excessive use can decrease digestive enzymes and increase bloating gas production as a result, so avoid excessive tums. Avoid calcium from dolomite, bonemeal, and oyster shells (they have lead contaminants in them). Calcium mixed with Vitamin D and magnesium is an excellent supplement for bone health, especially as a 2:1 ratio (calcium 500mg/magnesium 250 mg). People absorb calcium better in small quantities through the day rather than a single large bolus. Be aware that calcium interacts with many medications and interferes with absorption of some medications, such as tetracyclines, biphosphonates, aspirin, and others. Some medications deplete calcium, such as aluminum antacids, steroids, anticonvulsannts, which deplete calcium supplies in the body. Calcium mixed with thiazide diuretics can lead to high, toxic blood levels of calcium in some people. Of note, a study recently suggested that calcium supplements may increase the risk of heart disease in some people by depositing in the coronary vessels. This appears to be not true.
  • Vitamin D is also an important component to bone health and body health. Deficiency in this vitamin has been associated with Alzheimer’s disease, autoimmune disorders, stroke, and musculoskeletal decline, among other things. Optimally, blood levels should be 30-80 ng/ml. The RDA for vitamin D in people aged 50-71 is 400 IU/day and for those over 70, the RDA is 600 IU/day. You can take up to 4000 IU/day safely per some sources. Vitamin D3 is the most active form of Vitamin D. Vitamin D is neccessary for optimal calcium and magnesium absorption in the gut. Our western style diet results in a high acid intake that leaches our bones. Chronic low grade acidosis in the body with our acidic diet, leads to bone derangement, especially in people with poor kidney function.
  • The shift to eating a better acid-base balanced diet can be made by including more plat foods in your diet (they are rich in alkaline materials). Consider this to boost bone health.
  • The recommended intake of protein is .4-.6 gm of protein per pound of weight. The average protein intake should be 55-100 gm per day. Protein content is high in beans, peas, and lentils (7 gm in a half cup) and high in poultry, fich, and lean meat (7 gm in 10 oz meat). Consider eating nuts and seeds for protein supplementation ( 7 gm in  1/4 cup, especially pumpkin seeds, which have 18 gms!)

Insane Medicine – New future treatment for obesity –

Insane Medicine: incretins and dpp
Incretins and DPP . GLP-1 stimulates the release of insulin to help lower blood sugar after a meal. It also prevents glucagon release. Glucagon causes the breakdown of glycogen stores in the liver into glucose, thereby raising blood sugar. DPP-4 is an enzyme that inactivates GLP-1.
Action of GLP
Action of GLP – as before, GLp is produced in the stomach in response to food and causes the pancreas to increase insulin production and decreases glucagon expression.
gip and glp actions
Gip and glp actions

Our generally bad diets, high in fat and processed sugar result in obesity and metabolic derangements. As a result of years of insulting foods, the body’s cells reprogram themselves in such a way that even if one exercises and diets well, it remains difficult to lose weight.

Bariatric surgery has been effective in producing significant weight loss and metabolic changes, allowing one to have less appetite, burn more calories, lose fat, and lose weight.

In the diagram above, the body normally responds to a meal by producing GLP-1 and GIP, which act on the pancreas to produce more insulin to lower the blood sugar. GLP-1 also prevents the secretion of glucagon, which is a hormone that causes the production of glucose from fat. In type 2 diabetes, the body does not respond to GLP-1, GIP, or glucagon as it should, so the GLP-1 no longer suppresses appetite or promotes insulin production after a meal. The failure of glucagon to be active in the body results in fat accumulation.  Bariatric surgery has been the only method to boost the effective functioning of GLP-1, GIP, and glucagon.

Researches at the Helmholtz Diabetes Center in Munich, Germany have produces a protein that takes structural pieces of GLP-1, GIP, and glucagon and merges them into a single functional unit.  This drug, when injected into rats, increased glucose lowering, fat burning, and weight loss in obese rats through clear metabolic changes. This resulted in test rats to lose up to a third of their body weight! A pill and no surgery…sounds like a great opportunity!

Insane medicine: Pregnant mothers may need to watch their fat intake during pregnancy – it may affect their children!

Insane medicine - Fat mice get fat by eating fat diets. The effect damages their progeny.
Insane medicine – Fat mice get fat by eating fat diets. The effect damages their progeny.
  • The average American diet has 37% fat content. The recommended amount is 25-35% according to the 2010 dietary guidelines. Four studies have shown the bad impact that high fat consumption during pregnancy has on the fetus.
  • Mice fed 45 % fat diets during pregnancy demonstrated deficits in memory with higher anxiety and depression scores as well! What’s worse is there was epigenetic effect as well – the following generation of mice displayed memory loss and behavioral change as well. Here is the link: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=3527&sKey=f830412f-200d-4363-8e53-e8af37236afe&cKey=f00a8887-5be2-467f-a500-480d7b3bcac8&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
  • A study in rats also showed that the mother’s diet, if high in saturated fat and branched chain amino acids(BCAA), would prime the microglia of their offspring. Microglia are the mmune cells of the brain and will secrete pro-inflammatory cytokines in the hippocampus (a learning center). Also high levels of BCAA compete with tryptophan transport across the blood brain barrier. When there is less tryptophan in the brain, the brain makes less serotonin which then results in anxiety! The pups were found to have depression and anxiety scores that were much higher than pups born to mothers who ate a more fat-restricted diet. Here is the link: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=8d86b6b5-65d9-4dc4-9b97-53b5a5db4027&cKey=529d5e00-6f15-426c-8ee3-c9c61424e666&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
  • Other studies demonstrated that a high fat diet in the pregnant mother causes the down-regulation of oxytocin systems in the brain of offspring and causes anxiety to be prevalant in the progeny. This effect does not occur in the pups of normal fed pregnant female rats. In this study it was found that the fewer numbers of oxytocin-positive neurons within the PVN (paraventricular nucleus), the more anxious the rats were as adults. Oxytocin projections to the brainstem acts as an appetite suppressant,  hence leading to overeating in the progeny of overfed pregnant females. Oxytocin also plays a role in maternal behaviors as well. Mother rats literally groom their daughters to be attentive or neglectful mothers themselves and this is associated with the presence of normal numbers of oxytocin projections. If a rat has fewer oxytocin projections, they will be neglectful parents more likely. Hence multiple pathways of brain function  may be affected in the young of a high-fat diet mother. Here is a link: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=93a801db-9e49-4d58-b917-97948ec69a18&cKey=74611e5c-0fa7-4ff0-9276-b94be31da2df&mKey=54c85d94-6d69-4b09-afaa-502c0e680ca7
  • These effects also occur in primate studies as well – monkeys whose mothers are fed high fat diets have fewer dopamine projections to the nucleus accumbens ‘reward center’ of the brain. As a result, they have a reward deficiency when they eat food and don’t get satiated at a normal level of food. Rather, they  must take in more food to get the same amount of reward as another monkey that came from a normal-fed mother and had normal dopamine projections in the brain. Thus they get fatter.
  • Dietary guidelines recommend a diet of 25-27% fat. See this link for the recommendations of a standard diet:  http://www.health.gov/dietaryguidelines/dga2010/DietaryGuidelines2010.pdf  However, the average person takes in 37% fat or more!! See this link showing how much we really take in:  http://jn.nutrition.org/content/140/10/1832.long
  • We eat more than we think. We need to recognize that our food choices and stress patterns can affect our children through epigenetic mechanisms especially. We can set up our children for failure. These studies are done in standard models for humans and show the impact high fat diets in pregnancy  have on their children: Memory deficits, anxiety, depression, and future weight problems may echo the studies in rat and monkey populations.  The apple doesn’t fall far from the tree, for it seems that overweight parents have overweight children. Food for thought!!
  • http://fatmouse.org/

Insane Medicine – Brown fat may be the anti-fat! Exercise is the key to activate it and lose weight!

Insane Medicine - Brown fat may be involved in glucose and fat metabolism
Brown fat appears to be involved in glucose and triglyceride regulation as well as insulin sensitivity. It’s absence or failure in some people may lead to obesity.

brown fat

  • Our body has three types of adipose (fat) cells: white, brown, and Brite fat. White fat is what we classically refer to as fat.  It has become apparent that fat is not just a storage agent of triglycerides (fat), but that it’s behavior can affect the process of metabolic syndrome in obesity, in which a person has cholesterol/triglycerides issues, and insulin insensitivity. This leads to high cholesterol and diabetes.The paper links below list some theoretical information about how brown fat activation may be a key to weight loss.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579148/

http://download.springer.com/static/pdf/938/art%253A10.1007%252Fs13679-014-0125-8.pdf?auth66=1416110283_90ed8c70da94490ed1b81556e63a5176&ext=.pdf

http://link.springer.com/article/10.1007/s13679-014-0125-8

  • Brown fat (BAT) has been found in humans but seems to disappear by the age of two. It is involved in heat generation (without shivering being the cause of this heat production) Brown fat is stimulated by cold exposure and decreases with age and with weight increases. The higher your BMI (body mass index) the less brown fat you have. Brown fat has a role in glucose disposal and triglyceride clearance by sucking it from the blood stream and generating heat. It generates the heat by ‘uncoupling oxidative phosphorylation” in which the mitochondria (powerhouses of the cell) don’t produce ATP (energy units) as they usually do with their proton energy gradients, but rather generate heat.
  • BAT is activated by cold and causes the cells to take up more glucose to produce heat. Insulin also causes the brown fat to take up glucose. It has been found that capsinoles (found in chili peppers) stimulates thermogenesis in brown fat.
  • Decreased activity of BAT results in metabolic syndrome in which there are glucose homeostasis problems, lack of insulin sensitivity, and poor triglyceride clearance, leading to diabetes and high cholesterol. Again BAT decreases with age but increases with cold exposure and adrenergic stimulus (adrenaline). Brown fat locally produces leptin and interleukin 6 as local hormones and has a substance UCP-1 on it’s surface (white fat does not have this)
  • White fat is the common fat you recognize and acts as a storage tank for triglycerides, producing leptin, adiponectin, and adipokines locally. It does not have UCP-1 on it. It comes from a different origin than brown fat.  Brown fat appears to originate from a myogenic (muscle) precursor!
  • Brite fat is the third type of fat, similar to brown fat in many ways and can convert to brown fat. This process is referred to as browning. This occurs by contact with Irisin, a hormone myokine made in the muscle in response to activity/exercise.  Irisin recruits Brite adipocytes to become brown adipocytes.
  • Brown fat makes up 5% of the basal metabolic rate and may potentially be involved with up to 15% of the daily energy expenditures!

The summary is that brown fat, if it can be turned on, may be a way to decrease weight and reverse glucose intolerance  (diabetes) and cholesterol problems in obese people, who have less brown fat than their thin peers. Current options are: Exercise to turn on the brown fat and increase your intake of capsinoles (chili peppers) which may stimulate thermogenesis. Cold exposure also turns on brown fat, but that is probably unsafe as an option, nor pleasant! Science is working on other solutions as well.

Insane Medicine – Environmental Obesity

Insane Medicine -Some obesitty-causing factors may be environmental in origin
Insane Medicine -Some obesitty-causing factors may be environmental in origin.
  • There are many additional environmental ingredients added to our food that potentially have a bad impact on our health. These additives are used to enhance food flavors or extend their shelf-life. There may be some connection to the increased rates of obesity and these additives.
  • Certainly increased food intake, decrease activity, and increased processed foods have added to the obesity epidemic, there is some indication that environmental chemicals may be a component.
  • Phthalates: Used in food production during processing and production can increase fat storage in humans.
  • Organotins in seafood and shellfish modify fat storage and energy metabolism.
  • Heavy Metals in rice, spinach, lettuce, and some herbs causes endocrine disruption and other metabolic issues.
  • Bisphenol A in polycarbonate bottles and canned food disrupts the endocrine system.
  • Persistent organic pollution in oils, seafood, berries, animal products disrupts sugar and fat metabolism.

BPA is released more from containers when they are heated or an acidic food is placed in them, whereas persistent organic pollutants enter the food chain as animals and plants accumulate the toxic materials ans pass it to others. The bottom line is a disruption of endocrine regulation.

How to avoid the toxins: Never heat items in a plastic container and do not place plastic containers in the dishwasher. Plastic items with the codes 3 (Phthalates), 6 and 7 ( contains BOA) should be avoided. It is best to make your food from scratch to avoid processed foods that may have these items in them as flavorings or to enhance shelf life.