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diets

  • Taking Supplementation Seriously Part IV

    In past articles, we presented the case for insuring nutritional sufficiency of the essential vitamins and minerals through supplementation. There is little debate that these micronutrients are requisite for human survival, and that their supplementation may be an apt course for some. A healthy diet also provides several other nutritionally-beneficial elements which, like the vitamins and minerals, are not always present at optimal levels and thus can potentially benefit from supplementation.

    Here is a list of five dietary supplements that are worth considering as additions to the multivitamin. They are not meant to represent the "best" or "most useful" of the supplement field (which has little meaning given the individuality of metabolism); rather, these choices represent common dietary constituents that primarily function to broadly improve health and well-being (as opposed to addressing a single aspect of it). Each has a defined, critical role in normal human metabolism, and all but one are only obtainable through the diet.

    Omega-3 fatty acids and whey protein are sources of essential fatty and amino-acids, the two remaining classes of essential nutrients after the vitamins and minerals. Fiber supplements provide this oft-deficient dietary macronutrient, which along with probiotic bacteria are a major determinant in intestinal function and the maintenance of healthy gut microflora. Supplementing with the nutritionally non-essential Coenzyme Q10 can augment the levels of this general purpose fat-soluble antioxidant and critical component for cellular energy generation, which may be of particular significance for older consumers.

    Note that this list is a starting point; there are many additional dietary supplements that truly "supplement" the diet with nutrients that are often missing or suboptimal (phytonutrients such as carotenoids, isothiocyanates, and polyphenolic antioxidants are notable examples), as well as several well-studied natural ingredients that address specific health concerns but may not be "normal" constituents of the diet (herbal supplements such as milk thistle or saw palmetto fall into this category).

    Omega-3 fatty acids. Omega-3 fatty acids are long-chain polyunsaturated fatty acids from fish, shellfish, algae, or seed oils that have well-established roles in human nutrition, both as building blocks for the cell membranes of the brain, and as precursors to the human body's own natural anti-inflammatory system. Sufficient intake of omega-3s has been associated with reduced risk of heart disease, may facilitate healthy levels of circulating cholesterol and triglycerides, and may help maintain a healthy heartbeat and blood pressure. A balanced inflammatory response also relies on sufficient omega-3 fatty acids for the synthesis of endogenous anti-inflammatory factors.

    Alpha-linolenic acid (ALA), a constituent of seed oils from flax, perilla, and chia, is an essential nutrient for humans. The principle omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from marine oils are not considered essential to human nutrition (we can make these from dietary ALA), but there is evidence some people may have trouble synthesizing sufficient levels of these fatty acids on their own, making them a good supplement choice. Omega-3 fatty acids from krill (a cold water crustacean) are in a potentially more bioavailable form (phospholipids) and contain high levels of the fat soluble antioxidant astaxanthin. Initial studies of krill oil suggest it may have a more potent lipid-lowering effect than other cold-water fish oils, meriting its choice as an omega-3 source.

    Whey Protein. It's not a capsule, and might be better described as a food product, but whey deserves consideration for increasing the amount of high-quality protein and essential amino acids in the diet. Whey protein is the "soluble" protein fraction from milk, and is commonly sold as a concentrate (most often about 70 percent protein with very low amounts of milk sugar or fat) or isolate (>90 percent protein, usually fatand lactose-free ), as well as in flavored pre-mixes or ready to drink beverages. Diets which are higher in protein have been associated with better glycemic control, normalized blood lipids, and have been shown to promote greater fat reduction, thermogenesis, and energy expenditure than high carbohydrate or high fat diets. Protein can also be more satiating than other macronutrients. "Fast proteins," like whey, are quickly digested and absorbed, which results in large, rapid increases of amino acids in the bloodstream following a meal, signaling fullness. Compared to other common protein supplements (soy, casein), whey exhibits superior appetite suppression when taken with a meal as 25 percent of total calories.

    Many of the health benefits of whey have been attributed to its high concentration of branched chain amino acids (BCAAs), a group of three nutritionally essential amino acids (leucine, isoleucine, valine). BCAAs serve as muscle fuel (which is why whey is often considered a “sports” supplement), but they may also stimulate the bodies basic satiety response. BCAAs also aid in fat loss, preserve lean body mass, and may help to lower insulin levels following a meal.

    Probiotics: Probiotics are living microorganisms, which upon ingestion in sufficient numbers, exert health benefits beyond general nutrition. Probiotic bacteria and yeast can reside on the surfaces of mucosal tissues (such as the gastrointestinal or upper respiratory tract) and provide a living barrier to environmental insults. Probiotic bacteria function in a variety of ways; they can inhibit the growth or block the attachment of rival pathogenic bacteria, they can improve the barrier function of mucosal membranes (providing protection from pathogens or toxins), they bolster immune function, produce vitamins, and enhance mineral absorption. Probiotic bacteria can play significant roles in systemic detoxification by trapping and metabolizing harmful dietary compounds or heavy metals. The production of the short chain fatty acids by probiotic bacteria in the intestines (from the fermentation of dietary fiber) improves the detox function of the liver and skin; this may also contribute to some of the anti-carcinogenic properties of dietary fiber.

    Probiotic supplements come in a myriad of forms and formulations, encompassing a wide variety of bacterial species and potency (probiotic potency is expressed in colony forming units—CFU—which is a measurement of the number of bacteria per serving.) A good starting point for general health maintenance would be a multi-strain product (having more than one type of bacteria) at a moderate potency (3–10 billion organisms); this is similar to the probiotic intake from a diet that contains fermented foods.

    Fiber Supplements: Fibers are polysaccharides (complex carbohydrates) that are indigestible by humans, yet have some significant roles in general health maintenance. The bulk of fiber and its resistance to digestion lend it satiating properties in the stomach; these same properties also cause it to increase the bulk of stool and hasten the transit of digested food through the intestines. This increase in gastric motility helps to minimize exposure of colonic epithelial cells to potential carcinogenic compounds or other dietary toxins. Dietary fibers can bind up bile acids and cholesterol, and prevent them from being re-absorbed; this facilitates the body’s ability to rid itself of excess cholesterol. Some fibers can also be specifically digested (fermented) by beneficial colonic bacteria into short chain fatty acids (like lactate or butyrate), which have their own health benefits throughout the body. Fermentable or prebiotic fibers (such as inulin and fructooligosaccharides) are available as supplements as well and are an appropriate complement to probiotics.

    There is convincing evidence that fiber intake reduces the risk of colon and breast cancers and cardiovascular disease; it has also been associated with healthy body weight, serum cholesterol levels, blood sugar control, and blood pressure. Unfortunately, the overwhelming majority of adults in the United States do not get the daily recommended intake of fiber, which is 38 grams/day for men 19–50 (30 grams/day for men over 50) and 25 grams/day for women 19–50 (21 grams/ day for women over 50). Even a modest increase to 20 grams a day from average current dietary levels has been estimated to reduce the rate of colorectal cancer by 40 percent. The fiber in our diets is heterogenous, containing several types of gums, pectins, lignans, cellulose, beta-glucans, fructans, and digestion-resistant starches. A good choice in fiber supplements would contain a mixture of multiple fiber types.

    Coenzyme Q10. Despite being the only member of the list that isn’t a nutritionally essential nutrient or a major component of the diet (young, healthy people can make sufficient CoQ10 for their metabolic needs), the potential health benefits of CoQ10 merit its consideration as part of a supplement regimen, especially in older consumers. CoQ10 is a fat-soluble substance that is an essential component of the energy production system in cells. It is found in each cell in the body, but is particularly concentrated in tissues which have large energy requirements (like the heart). There are also substantial amounts of CoQ10 in the blood, protecting circulating lipids (LDL and HDL) from oxidative damage. Supplemental CoQ10 has been the subject of numerous studies, particularly in applications for improving cardiovascular health (as in subjects with chronic heart failure, exercise-induced angina, or hypertension); it may also be protective of the cardiovascular system in diabetics. CoQ10 continues to be the subject of academic research, and is beginning to find acceptance as a supplement amongst mainstream medical practitioners.

    The average diet contains only a small amount of CoQ10, which is generally poorly absorbed (by some estimates, as little as two to three percent of dietary CoQ10 is absorbed). Variability in absorption also appears to be age-dependent; case reports suggest decreased fractional absorption in older patients. Several "enhanced absorption" strategies and products have been developed to overcome this hurdle, with improved uptakes verified by clinical data. Recently, the second naturallyoccurring form of CoQ10 (ubiquinol) has been introduced into the supplement market (CoQ10 supplements have typically been in the form of ubiquinone.) Ubiquinol is absorbed more efficiently than ubiquinone, especially in individuals who have difficulty absorbing CoQ10.

  • Carbohydrates are the most abundant biomolecules on our planet and in our food supply. They exhibit some of the largest differences in their metabolism by different members of the animal kingdom. At one extreme, herbivores can almost completely break down dietary plant material with the help of beneficial bacteria that dwell within their gastrointestinal tract; at the other extreme, true carnivores can’t process most dietary carbohydrates. Humans fall somewhere in between; we derive a great deal of nutrition out of some dietary carbohydrates, but are unable to process others.

    In our diets, digestible carbohydrates consist of sugars and starches, while the indigestible carbohydrates are the fibers and resistant starches1. Dietary sugars are predominantly monosaccharides (sugars consisting of a single unit, such as glucose and fructose) or disaccharides (sugars consisting of two monosaccharides linked together, such as sucrose and lactose). Starches are long chains (polymers) of many linked monosaccharide molecules, usually glucose.

    Monosaccharides are the preferred form by which sugars are absorbed from the intestines, therefore, starches and disaccharide sugars (sucrose, lactose) must be broken down by digestive enzymes before assimilation. Starches are fairly easily digested by the action of pancreatic enzymes, while disaccharide sugars are degraded by enzymes that dwell on the surface of the small intestines. The familiar lactose maldigestion (“lactose intolerance”) experienced by many individuals actually results from the lack of one of these intestinal enzymes (lactase, the enzyme that breaks down lactose into glucose and galactose).

    Fibers and resistant starches are carbohydrates as well. Like starches, fiber is composed of polymers of linked monosaccharide sugars. Unlike starches, however, fibers and resistant starches are not used as a source of calories; humans lack the necessary enzymes to break down resistant starches and fibers, therefore, they are not absorbed. Some soluble fiber and resistant starch is broken down by intestinal bacteria, the rest passes through the gastrointestinal tract intact.

    The majority of dietary carbohydrates are obtained from plant sources (fruits, vegetables, grains). In contrast to animal tissues, which are held together by mostly proteins, plants cells are held together by cellulose and lignin, two types of dietary fiber. The edible portions of plants are usually those that contain large amounts of storage carbohydrates, such as the kernels of grains (which store starches) or fruits (which store sugars). Smaller amounts of carbohydrates are found in animal products; carbohydrates constitute only about one percent of the mammalian body2.

    ROLES OF DIETARY CARBOHYDRATES AND FIBER IN NORMAL METABOLISM
    Although they do not have the diversity in human metabolism as do proteins, dietary carbohydrates and fibers still have a number of fates:
    Fuel Source and Fuel Storage.

    As versatile as humans are in obtaining energy from a variety of macronutrients, the preferred energy source in our metabolism is the carbohydrate glucose. Under normal conditions, the brain uses glucose as an energy source almost exclusively, and most other tissues rely heavily on it. To accommodate the body’s need for glucose, most sugars and starches can be converted into glucose as they are absorbed and distributed amongst various tissue following a meal. Additionally, some amino acids from digested protein can also be converted into glucose (in true carnivores like cats, this is where most glucose comes from).

    Unlike other cellular energy sources (amino acids and fatty acids), glucose can be converted into energy in the absence of oxygen (anaerobic glycolysis). This makes glucose a critical source of quick energy during times when oxygen is scarce, such as during intense exercise.

    Glucose can also be stored for later usage, in the form of glycogen (“animal starch”). Glycogen is abundant in the liver, which stores about a day’s worth of glucose in order to provide enough energy to fuel the brain during periods between meals. Glycogen is also used to store glucose for use in muscles, which rely on it for quickly generating energy. If the dietary intake of carbohydrates exceeds what is needed for immediate energy and glycogen reserves, then the excess is converted to fat for long-term storage.

    Precursors to other biomolecules. Carbohydrates are used to make other important biomolecules. These include: glycosaminoglycans (such as chondroitin, keratin, and hyaluronic acid), important constituents of joints and connective tissues; nucleic acids (DNA and RNA are partially constructed from the sugar ribose); as well as other amino acids and fatty acids for making new cellular proteins and cell membranes.

    Stimulation of digestion. Fiber, despite its non-nutritive value, still has evolved important roles in human physiology. The bulk of insoluble fibers helps digested food to move more easily through the intestines and be readily eliminated from the body. Soluble fibers and resistant starches can provide a source of energy for intestinal bacteria, which themselves provide a number of health benefits, including the stimulation of immunity, protection from pathogenic bacteria, and enhanced absorption of minerals from the diet. Prebiotics, a subset of soluble fiber, have gained attention in recent years in their ability to be selectively fermented by gut flora for a diversity of potential health-promoting benefits3.

    SPECIFIC HEALTH BENEFITS OF CARBOHYDRATES AND FIBER
    Many of the health benefits realized by modifying carbohydrate intake involve altering patterns of consumption: reducing intake of sugars, and increasing intake of fiber. For example, recent emphasis on increased intake of whole grains (which contain significantly more fiber, phytonutrients, and protein than do refined cereal flours) has resulted from several studies which suggest that its consumption may reduce the risk of certain cancers, diabetes, and cardiovascular disease4. Fiber intake, in particular, has been the subject of thousands of studies in humans and animals, in part for its ability to successfully reduce the risk of several diseases by different mechanisms:

    Reducing Chronic Low-level Inflammation. In contrast to the conspicuous inflammation that is characteristic of an injury or infection, chronic low-level inflammation can progress unnoticed. This potentially silent affliction has been associated with the progression of several diseases, including cancer, diabetes, cardiovascular, and kidney diseases. In an analysis of 7 studies on the relationship between weight loss and inflammation, increased fiber consumption correlated with significantly greater reductions in C-reactive protein (CRP), one indicator of low-level inflammation5. In these studies, daily fiber intakes ranging from 3.3 to 7.8 g/MJ (equivalent to about 27 to 64 g/day for a standard 2000 kcal diet) reduced CRP from 25–54 percent in a dose-dependent fashion. The Women’s Health Initiative Study also found significant inverse relationships with dietary soluble and insoluble fiber (over 24 g/day) and certain markers of chronic inflammation6.

    Promoting Healthy Blood Pressure. It is not clear how dietary fiber reduces blood pressure, but many studies have observed this trend. Fiber, when taken with a meal, may by reducing the glycemic index of foods and lowering the response of insulin following a meal (insulin may play a role in blood pressure regulation). Soluble fibers may also increase mineral absorption (such as calcium, magnesium, and potassium; all important for healthy blood pressure) by feeding intestinal flora, which lowers intestinal pH and establish a favorable acidic environment for mineral absorption7. Whatever the cause, at least thirty randomized, controlled clinical trials examined the effects of fiber in both hypertensive and normotensive patients. Across all participants, increased fiber intake demonstrated modest average reductions in systolic (1.13–1.15 mm Hg), and diastolic (1.26–1.65 mm Hg) blood pressure89. Amongst hypertensive patients, the average blood pressure reductions were much larger: A significant average reduction in both systolic (-5.95 mm Hg) and diastolic (-4.20 mm Hg) blood pressure was observed over 8 weeks in trials where hypertensive participants increased their daily fiber intake9.

    Promoting Healthy Levels of Blood Lipids. High-fiber diets have been associated with lower prevalence of cardiovascular disease (10). When included as part of a low-saturated fat/low cholesterol diet, dietary fiber can lower low-density lipoprotein cholesterol (LDL-C) by 5–10 percent in persons with high cholesterol, and may reduce LDL-C in healthy individuals as well10. Dozens of controlled clinical trials have shown the cholesterol-lowering potential of dietary fibers including soluble oat fiber, psyllium, pectin, guar gum, b-glucans from barley, and chitosan3,12,13.

    Soluble fibers lower cholesterol by several potential mechanisms (3). They may directly bind cholesterol in the gut, preventing its absorption. The high viscosity of soluble fiber and its ability to slow intestinal motility may help to limit cholesterol and fat uptake as well. Fiber can also increase satiety, which can limit overall energy intake14,15. Lowering Uric Acid. Elevated blood uric acid (hyperuricemia) is a risk factor for kidney disease, cardiovascular diseases, and diabetes; it is also a primary cause for gout16. Fiber intake may lower blood uric acid levels. A significant inverse relationship between fiber intake and hyperuricemia risk was established by analyzing dietary fiber intake data from over 9000 otherwise healthy adults participating in the National Health and Nutrition Examination Survey (NHANES) from 1999–2004. Based on these data, participants with high fiber diets (over about 19 grams fiber/day for the average 2000 kcal diet) had a 55 percent reduction in hyperuricemia risk compared to those on lower fiber diets (<9.2 g fiber/day)17. While these mechanisms for this reduction is unknown, dietary fiber may reduce the absorption of purines from the diet, one of the inciting factors for hyperuricemia.

    HOW MUCH CARBOHYDRATES AND FIBER SHOULD I BE GETTING?
    The amount and composition of carbohydrates in the “ideal” diet is amongst the most heavily debated topics in nutrition. There are scientifically-substantiated merits to both the “low-carb” and “low-fat, high-carb” diets in terms of reducing disease risk and maintaining a healthy body mass index (these will be discussed in greater detail in a future article). The common ground between the two schools of thought is that the average Western diet probably contains too little fiber, and too much refined grains and added sugar. A low-fiber/high-sugar diet, when coupled with excessive caloric intake, has been associated with significant increases in the risk for a number of ailments, including obesity, insulin resistance/type II diabetes, and cardiovascular disease.

    As mentioned previously, the benefits of dietary fiber are numerous. The average daily fiber intake in the American diet, based on data from 2007–2008 NHANEs survey, is about half of the 28 grams/day recommendation by the Institute of Medicine (IOM). Significant numbers of people consume even less than the national average. The highest intakes of dietary fiber are associated with the lowest disease risks; for several observational studies, the greatest risk reductions required intakes exceeding the IOM recommendations.

    In contrast, the American diet contains no shortage of refined grains or sugars. The U.S. Department of Agriculture estimates average grain consumption at about 33 percent more than 6 oz./day recommended in its Dietary Guidelines for Americans. Most of this grain is refined; the same group estimates Americans consume only one-third of the recommended 3 oz./day of whole grains18,19.

    Analysis of data from the last NHANEs survey (2007–2008) determined that Americans consume an average of 120 grams/day of total sugars (about 30 teaspoons), most of which are added sugars. This amounts to approximately 480 kilocalories of energy per day. Most of these sugars come from sweetened carbonated beverages (~37 percent); other top sources include desserts and fruit drinks (fruitades and fruit punches). While arguments can be made that it is the added fructose or corn syrup are particularly dangerous to health (there is evidence that supports and refutes this hypothesis), or that sugar is additive and contributes to overeating (animal models may support this claim), added sugar clearly contributes a significant amount of calories to the average diet, and in many cases displaces essential nutrients20,21.

    To read the series on Macronutrients:

    References:

    1. Fardet A. New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutr Res Rev 2010 Jun.;23(1):65–134.
    2. Engelking L. Textbook of Veterinary Physiological Chemistry. Updated 2nd ed. Burlington, MA: Academic Press; 2011.
    3. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999 Jan.;69(1):30–42.
    4. Higgins JA. Whole grains, legumes, and the subsequent meal effect: implications for blood glucose control and the role of fermentation. J Nutr Metab 2012;2012:829238.
    5. North CJ, Venter CS, Jerling JC. The effects of dietary fibre on C-reactive protein, an inflammation marker predicting cardiovascular disease. Eur J Clin Nutr 2009 Aug.;63(8):921–33.
    6. Ma Y, Hébert J, Li W, Bertone-Johnson E. Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Nutrition 2008;
    7. Greger J. Nondigestible carbohydrates and mineral bioavailability. J Nutr 1999.
    8. Streppel MT, Arends LR, van t Veer P, Grobbee DE, Geleijnse JM. Dietary fiber and blood pressure: a meta-analysis of randomized placebo-controlled trials. Arch Intern Med 2005 Jan.;165(2):150–6.
    9. Whelton SP, Hyre AD, Pedersen B, Yi Y, Whelton PK, He J. Effect of dietary fiber intake on blood pressure: a meta-analysis of randomized, controlled clinical trials. J. Hypertens 2005 Mar.;23(3):475–81.
    10. Badimon L, Vilahur G, Padro T. Nutraceuticals and atherosclerosis: human trials. Cardiovasc Ther 2010 Aug.;28(4):202–15.
    11. Anderson J, Randles K. Carbohydrate and fiber recommendations for individuals with diabetes: a quantitative assessment and meta-analysis of the evidence. J Am Coll Nutr 2004.
    12. AbuMweis SS, Jew S, Ames NP. -glucan from barley and its lipid-lowering capacity: a meta-analysis of randomized, controlled trials. Eur J Clin Nutr 2010 Dec.;64(12):1472–80.
    13. Baker WL, Tercius A, Anglade M, White CM, Coleman CI. A meta-analysis evaluating the impact of chitosan on serum lipids in hypercholesterolemic patients. Ann Nutr Metab 2009;55(4):368–74.
    14. Brighenti F, Casiraghi M, Canzi E. Effect of consumption of a ready-to-eat breakfast cereal containing inulin on the intestinal milieu and blood lipids in healthy male volunteers. Eur J Clin Nutr 1999; Pages 726–33.
    15. Li S, Guerin-Deremaux L, Pochat M, Wils D, Reifer C, Miller LE. NUTRIOSE dietary fiber supplementation improves insulin resistance and determinants of metabolic syndrome in overweight men: a double-blind, randomized, placebo-controlled study. Appl Physiol Nutr Metab 2010 Dec.;35(6):773–82.
    16. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: The National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 2011 Oct.;63(10):3136–41.
    17. Sun SZ, Flickinger BD, Williamson-Hughes PS, Empie MW. Lack of association between dietary fructose and hyperuricemia risk in adults. Nutr Metab 2010;7(1):16.
    18. Grotto D, Zied E. The Standard American Diet and its relationship to the health status of Americans. Nutr Clin Pract 2010 Dec.;25(6):603–12.
    19. U. S. Department of Agricuture USDOHAHS. Dietary Guidelines for Americans 2010. 2011 Jan.;:1–112.
    20. Avena NM, Rada P, Hoebel BG. Sugar and fat bingeing have notable differences in addictive-like behavior. Journal of Nutrition 2009 Mar.;139(3):623–8.
    21. Berner LA, Avena NM, Hoebel BG. Bingeing, self-restriction, and increased body weight in rats with limited access to a sweet-fat diet. Obesity (Silver Spring) 2008 Sep.;16(9):1998–2002.

  • The official start of summer is just around the corner. Many people might find themselves entrenched in diet and detox programs to shed those extra pounds for tank top confidence. My tried-and-true Fat Flush Plan offers daily detox, healing foods, metabolism-revving spices, calming rituals, and more that has helped thousands around the world find lasting success. When you're at home, sticking to your healthy eating plan is easy, with the right weekly preparation. But, what about when you're traveling or enjoying a dinner out? I have found that times like these can be the most challenging for folks and are a venerable time to "fall off the wagon." In this preview from my book, The NEW Fat Flush Plan—a full update of The New York Times Best Seller—I share my tips to make three popular genres Fat Flush-friendly while dining out.

    ITALIAN FOOD

    This is the cuisine where, at least in the type of Americanized Italian food in the United States, you have to watch to not overdo carbs such as pasta, beans, and that delicious garlic bread. Thus you might want to have the server take the bread basket away as soon as you sit down. If you are really hungry, then order an appetizer right away. Grilled Portobello mushrooms or an artichoke (hold the breading) is a tasty starter. You may want to indulge in a Caesar salad, which is perfectly Fat Flush legal. Just ask for it without croutons and get the dressing on the side. And if you have a taste for anchovies in the Caesar dressing, go for it! They are high in the omega-3s, although a bit on the salty side. The best news at an Italian restaurant is that you usually can get a wide variety of delicious, colorful veggies that are not as easily available elsewhere, such as zucchini, peppers, cauliflower, eggplant, and spaghetti squash. In addition, you can typically get a leafy green, such as spinach or escarole, here as well. Sautéed with onions, fresh garlic, and a little lemon in olive oil or chicken broth, these vegetables are out of this world and very Fat Flush friendly.

    And oh yes, there's that cheese—the mozzarella, ricotta, and provolone. For those of you on the Lifestyle Fat Flush eating plan, keep them to a tasty minimum and use them as a condiment, please. You can even have your pesto (that sensational combination of olive oil, garlic, basil, pine nuts, and Parmesan cheese) and eat it too. Ask for it on the side so that you can enjoy a couple of tablespoons slowly and deliberately. Do not overlook the veal dishes (the Marsala, piccata, or scaloppini), which are usually quite outstanding in the finer Italian restaurants. Watch to make sure you are adhering to high-quality oils like olive oil, and learn to lemonize by ordering several lemon wedges that can help emulsify excess oil.

    CHINESE FOOD

    Things are really simple when you go to Chinese restaurants. Just find out which dishes can be made to order and request no MSG, sugar, salt, or soy sauce. If you must, you can always add your own soy sauce at the table. If the oil is anything other than sesame or peanut oil (and there's no allergy to peanuts), then order your food steamed. I always request a stir-fry that uses chicken broth and is made from such combinations as beef, chicken, seafood, or tofu with snow peas, water chestnuts, bean sprouts, broccoli, scallions, bamboo shoots, and bok choy (Chinese cabbage).

    If you are in the Lifestyle phase and want a good vegetarian meal, try Buddha's Delight, a mix of vegetables and rice cellophane noodles that can be stir-sautéed in vegetable broth. Buddha's Delight can be modified for any Fat Flush phase by omitting the noodles. You can have tofu added to the dish with a side of steamed veggies topped off with scallions, garlic, and a bit of Chinese fivespice powder, a delightful mixture of unique spices related to cinnamon. Most of the soups offered in a Chinese restaurant are made with lots of cornstarch—including egg drop soup—so it is best to skip the soup course. On the Lifestyle Fat Flush, lo mein dishes—cellophane or mung bean noodles with some chicken, beef, shrimp, or other kinds of seafood—also might be appealing. Just remember that those oyster and black bean sauces are loaded with salt, which can result in boggy, watery tissues. Try a bit of the hot mustard, minced garlic, scallions, and even some Chinese five-spice powder instead. As for the fortune cookie—by all means have fun and open it. Read your fortune, and then leave the cookie behind. Also, try eating with chopsticks. It may help to slow you down and enhance your digestion as a result.

    MEXICAN FOOD

    You may want to select such entrées as chicken, shrimp, or beef and eat them without the tortilla unless you are on the Lifestyle Fat Flush. Look for main dishes with fish, chicken, or beef that can be prepared with onions, tomatoes, and peppers (such as Veracruz snapper), or look for dishes that can be sautéed in olive oil with a touch of garlic. If you are on the Lifestyle Fat Flush, a tasty Mexican soup (such as black bean soup) would be a great way to start your meal. If not, then how about some guacamole (loaded with the healthy monounsaturated fats) with lots of fresh lemon or lime juice? Salsa is probably your best all-over topping. Use the sour cream and cheese as condiments, with just a dollop or a few sprinkles here and there for flavor. If you are fortunate enough to locate an authentic Mexican restaurant, such foods as squash blossoms, jícama, and chayote cactus are treats for the palate. If you happen upon a restaurant on the other end of the American-Mexican food spectrum, like Tex-Mex, you can order a beef, chicken, or seafood fajita with extra vegetables, and if you are not yet in the Lifestyle Phase, eat your fajita without the corn tortilla. Be sure, as always, to watch the kind of oil that the restaurant uses to cook the fajita meat and veggies, and ask them to use as little oil as possible.

    To take back your health and reach your goals, at home or away, pick up your copy of The New Fat Flush Plan.

     

  • It is New Year's resolution time and one of the perennial resolutions for many Americans is, "this year I am going to lose weight and keep it off."

    Literally two thirds of Americans are overweight or worse, so there are a lot of such resolutions being made. Like gym memberships, however, there are far more resolutions initially undertaken than followed through. Nevertheless, this time around things can be different. One key is that the weight loss strategy adopted should also be one that can be continued as a normal everyday diet pattern. There is no reason that this should not work as long as realistic goals are adopted. Life, as the observation goes, is a marathon, not a sprint. Moderate, yet well thought-out changes in the diet regarding the ratios of protein, carbohydrate and fat can yield durable results over a span of three to six months. Similarly, care in terms of the timing of food intake, consumption of fiber and phytonutrients, and so can yield big rewards.

    High Protein Beats High Carbohydrate During Weight Loss

    Let's start with the initial weight loss goal. Ads for diet products and programs often promise "ten pounds in ten days," but such promises, even were they true, are never lasting. The body resists extreme changes and, in the end, the body always wins. A better approach is to coax the body in the desired direction so that it becomes more metabolically flexible and thus can burn fat for energy rather than storing it. This means overcoming roadblocks such as poor blood sugar control dieting-induced loss of lean tissue. The protein-to-carbohydrate make-up of meals is important here. Indeed, this ratio and not the amount of fat in the diet is determining.

    Realistically, reducing energy intake by approximately 500 calories per day is sufficient for many dieters initially to experience weight loss of 1 – 2 pounds per week. The catch is that weight loss based only on restricting calories has a poor record for improving impaired glucose tolerance and typically leads to a loss of the more actively calorie-metabolizing lean body tissues. A study with obese subjects published in the journal BMJ Open Diabetes Res Care demonstrates that this need not be the outcome of dieting.1 One hundred percent of obese adults using a high protein (HP) moderately calorically-restricted diet, but not those on a similarly restricted high carbohydrate (HC) diet achieved a return to normal glucose tolerance in addition to benefits in their markers for cardiovascular and inflammatory health. On the HP diet there was an increase in the percentage of lean body mass and a decrease in the percentage of fat body mass with weight loss whereas the HC diet led to a decrease in the percentage of lean body mass along with a decrease in the percentage of fat body mass. The change in glucose tolerance/blood sugar levels and the improvement in the percent lean body mass demonstrated with higher protein intake and restricted carbohydrate intake are highly desirable outcomes. The key was substituting protein for carbohydrate calories.

    For this study, researchers randomized 24 women and men with elevated fasting glucose levels in the pre-diabetic range to either a HP diet (30 percent protein, 30 percent fat, 40 percent carbohydrate; n=12) or a HC diet (15 percent protein, 30 percent fat, 55 percent carbohydrate; n=12) for a study lasting six months. All meals were provided to these subjects for the six months. At the start of the study and at its conclusion, tests were performed to determine oral glucose tolerance and serum insulin levels as well as a variety of other parameters indicative of metabolism and inflammation. X-ray scans were conducted to determine body composition in terms of the percentage of lean and fat tissue.

    The differing diets led to dramatically different results. According to the authors of the paper, on the HP diet 100 percent of the subjects exhibited remission of their pre-diabetes to normal glucose tolerance whereas only 33.3 percent of subjects on the HC diet exhibited this remission. Moreover, the high protein arm subjects exhibited significant improvement in (1) insulin sensitivity (p=0.001), (2) cardiovascular risk factors (p=0.04), (3) inflammatory cytokines (p=0.001), (4) oxidative stress (p=0.001), and (5) increased percent lean body mass (p=0.001) compared with the HC diet.

    In terms of the findings likely to be of particular interest to most dieters, it should be pointed out again there was an increase in the percentage of lean body mass and decrease in the percentage of fat body mass with weight loss on the HP diet. In contrast, there was a decrease in the percentage of lean body mass with weight loss on the HC diet although the percentage of fat body mass did decline as expected. Importantly, both metabolic parameters and inflammation markers were improved only on the high protein / reduced carbohydrate, moderately calorically restricted diet.

    Doesn't Eating Fat Make You Fat?
    Keeping weight off after a diet is the real challenge. The fact that in dieting it is mostly the caloric restriction that leads to weight loss and not diet specifics has been known for decades.2 For instance, in 1996 a study was published that compared diets much more disparate than the one described above.3 Forty-three obese adults were randomly assigned to receive diets containing 1,000 calories/day composed of either 32 percent protein, 15 percent carbohydrate, and 53 percent fat or 29 percent protein, 45 percent carbohydrate, and 26 percent fat. There was no significant difference in the amount of weight lost. Nevertheless, just as in the study above, fasting plasma glucose, insulin, cholesterol, and triacylglycerol concentrations decreased significantly in patients eating low-energy diets that contained 15 percent carbohydrate, but neither plasma insulin nor triacylglycerol concentrations fell significantly in response to the higher carbohydrate diet.

    A more recent study looked at moderate energy intake on a very high-fat, low-carbohydrate (73 percent of energy from fat, 10 percent of energy from carbohydrate and 17 percent of energy from protein) or low-fat, high-carbohydrate (30 percent of energy from fat, 53 percent of energy from carbohydrate and 17 percent of energy from protein) diet for 12 weeks.4 Unlike most modern diets, these were diets involving only minimally processed carbohydrates and fats. Despite expectations, the high fat diet did not raise LDL cholesterol; however, it did raise HDL cholesterol. According to one of the co-authors of the study, "the very high intake of total and saturated fat did not increase the calculated risk of cardiovascular diseases." "Participants on the very-high-fat diet also had substantial improvements in several important cardiometabolic risk factors, such as ectopic fat storage, blood pressure, blood lipids (triglycerides), insulin and blood sugar."5

    Therapeutic diets usually restrict either carbohydrates or fats. If fats are restricted, then the diet will tend towards an increased protein content. Most dieters will find that in the early stages, this high intake of protein will reactivate the thyroid and make life easier. There is plenty of clinical evidence to the effect that high protein snacks reduce calorie intake more than do snacks of carbohydrate, fat or alcohol for overweight individuals accustomed to the usual American mixed diet. And increasing protein intake to 25 percent of calories clinically has been demonstrated to increase both weight loss (by 75 percent) and fat loss (by 57 percent) more than was found on a protein intake of 12 percent. Still, eating protein is not a panacea (too much is too much6) and protein needs to be matched with goodly intakes of fruit and vegetables as well as the avoidance of refined carbohydrates for best results. Moreover, decades of research, as indicated above, demonstrates that carbohydrates need to be replaced by protein for best results.

    Does Gut Bacteria Play a Role in Weight Regain?
    Preserving lean tissue and improving various metabolic parameters certainly help to make dieting results more stable and lasting. An additional factor, one seldom considered, is the role of gastrointestinal bacteria in weight maintenance. Human experiments have demonstrated that changing the diet to artificially induce blood sugar regulation issues surprisingly quickly results in changes in the gut microbiome that cause these bacteria to release more calories from food than normally would be the case, for instance, by digesting supposedly indigestible fiber. Similarly, it is well established that individuals who are overweight, obese and/or diabetic often have substantially different gut microflora than individuals who are lean.7 Therefore, so-called yo-yo dieting and recurrent obesity might be at least influenced by the microbes found in the gut.

    A recent report in Nature casts further light on an aspect of this issue.8 As observed by one of the authors, Dr. Eran Elinav from the Weizmann Institute of Science in Israel, "we've shown in obese mice that following successful dieting and weight loss, the microbiome retains a 'memory' of previous obesity." Co-author Professor Eran Segal elaborated, "this persistent microbiome accelerated the regaining of weight when the mice were put back on a high-calorie diet or ate regular food in excessive amounts." One of the findings of this research is that the post-diet gut biome destroys certain flavonoids from the diet that influence energy metabolism. This interferes with energy release from fat. In post-dieting mice this leads to an accumulation of extra fat when they are returned to a higher-calorie diet. Experimentally, according to the paper, "flavonoid-based 'post-biotic' intervention ameliorates excessive secondary weight gain." This suggests that microbiome-targeting approaches may help with weight regain.

    Putting It Together
    Diets similar to the 30 percent protein, 30 percent fat, 40 percent carbohydrate diet described above have been proposed for several decades.9 In addition, the role of phytonutrients now is strongly supported. Both these aspects of good meal planning need to be addressed. A simple approach to meals is to make sure that roughly one third of the plate is covered with a protein source and one half or even two thirds of the meal plate is covered with the lightly cooked vegetable of your choice (salad does not count here; corn and carrots are counted as carbohydrates). Always eat this vegetable serving, which should be at least two cups of vegetables. Eat protein before eating any carbohydrates in the main meal for better digestion and better appetite control. (Classic European, Chinese and Japanese meal planning often arranges protein courses before carbohydrate courses.) Remember that vegetables are perfectly good carbohydrate sources and may well be consumed in the place of concentrated carbohydrates, such as rice and potatoes. Dieters also should consider supplementing with probiotics in conjunction with prebiotics. Finally, as noted in previous TotalHealth articles, when meals are eaten may be as important and what is eaten; never skip breakfast and avoid eating late in the evening or before bedtime.10

    References
    1. 1. Stentz FB, Brewer A, Wan J, Garber C, Daniels B, Sands C, Kitabchi AE. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial. BMJ Open Diabetes Res Care. 2016 Oct 26;4(1):e000258.
    2. 2. Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, Williamson DA. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009 Feb 26;360(9):859–73.
    3. 3. Golay A, Allaz AF, Morel Y, de Tonnac N, Tankova S, Reaven G. Similar weight loss with low- or high-carbohydrate diets. Am J Clin Nutr. 1996 Feb;63(2):174–8.
    4. 4. Veum VL, Laupsa-Borge J, Eng Ø, Rostrup E, Larsen TH, Nordrehaug JE, Nygård OK, Sagen JV, Gudbrandsen OA, Dankel SN, Mellgren G. Visceral adiposity and metabolic syndrome after very high-fat and low-fat isocaloric diets: a randomized controlled trial. Am J Clin Nutr. 2016 Nov 30. pii: ajcn123463. [Epub ahead of print]
    5. 5. University of Bergen. "Saturated fat could be good for you, study suggests." ScienceDaily. ScienceDaily, 2 January 2017. www.sciencedaily.com/releases/2016/12/161202094340.htm.
    6. 6. Rietman A, Schwarz J, Tomé D, Kok FJ, Mensink M. High dietary protein intake, reducing or eliciting insulin resistance? Eur J Clin Nutr. 2014 Sep;68(9):973–9.
    7. 7. Zhang Q, Wu Y, Fei X. Effect of probiotics on body weight and body-mass index: a systematic review and meta-analysis of randomized, controlled trials. Int J Food Sci Nutr. 2015 Aug;67(5):571–80.
    8. 8. Thaiss CA, Itav S, Rothschild D, Meijer M, Levy M, Moresi C, Dohnalová L, Braverman S, Rozin S, Malitsky S, Dori-Bachash, M. Kuperman Y, Biton I, Gertler A, Harmelin A, Shapiro H, Halpern Z, Aharoni A, Segal E, Elinav E. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature. 2016 Nov 24. doi:10.1038/nature20796.
    9. 9. Sears B, Ricordi C. Anti-inflammatory nutrition as a pharmacological approach to treat obesity. J Obes. 2011;2011.
    10. 10. Sellix MT. For Management of Obesity and Diabetes: Is Timing the Answer? Endocrinology.2016 Dec;157(12):4545–9.
  • Few people are surprised when told that it is relatively hard to lose weight in the fall heading into winter and relatively easy to lose weight in the spring. This is not just a matter of Thanksgiving, Christmas, New Year’s and the Super Bowl, although the grouping of these holidays hardly helps. Our bodies exhibit metabolic changes in preparation for the winter months and then tend to reverse at least some of these changes as the next year progresses. Hibernation is the classic example of these changes, but seasonal fluctuations in metabolism are shared by a quite large proportion of all mammals in temperate climates, including humans. More surprising to most of us is the fact that similar fluctuations in energy use and storage are tied to the twenty-four hour (circadian) cycle, as well, and these fluctuations are so strong that they may be more important than the usual dietary suspects — the amounts of carbohydrate, fat and protein in the diet — that typically are the targets of dietary advice.

    The Day/Night Cycle Exists Even For Genes
    A few years ago, a team of researchers experimented to learn if circadian rhythmic patterns apply to human fat tissue.1 In this particular case, they wanted to know if genes related to cortisol metabolism exhibited such rhythms in adipose tissue. (Cortisol is sometimes called the “fight or flight” hormone; it also plays a large role in weight gain.) Sure enough, the scientists found rhythmicity in cells from both men and women and in fat cells both from under the skin (subcutaneous) and around the abdomen (visceral deposits), with the amplitude of the circadian rhythmicity being greater in the visceral fat tissue genes.

    Yet another circadian pattern involving cortisol is important for weight gain in those under mild chronic stress, including the stress associated with diabetes. Under normal circumstances, the body tends to have a period of time during inactivity — our sleep cycle — in which cortisol levels in the blood exhibit a prolonged “trough” of reduced presence. Mild stress may only slightly elevate the total daily glucocorticoid level, yet still alter the way in which tissue receptors respond. In an animal model, healthy animals after several days of added glucocorticoid (via pellets under the skin) showed reduced adrenal and thymus weight, i.e., adrenal exhaustion and reduced immune response, and elevated insulin levels.2 This would seem to be similar to early stage Metabolic Syndrome as the animals struggle to regulate the excess sugar being released into the system by the glucocorticoid. In diabetic animals, insulin levels drop dramatically with continued glucocorticoid challenge, which means that the ability to regulate blood sugar also drops. Conversely, food intake and blood triglycerides increase in diabetic animals versus controls. Chronic exposure to cold in this model has the same type of effect as does added glucocorticoid, including the same disruption of the circadian rhythm of reduced glucocorticoid during the rest period. As the authors of this study observe, “studies in man suggest that perceived chronic stress also flattens the amplitude of the circadian cortisol rhythm by elevating trough and reducing peak levels; subjects who reported increased stress were abdominally obese, hyperinsulinemic and hypertensive.”

    With the foregoing evidence in mind, it is easy to grasp that activities such as exercise and meal timing may play significant roles in body weight and health. Hunger levels, the ability to dispose of meal calories and the degree of metabolic response, including metabolizing excess calories, all respond to stress levels and the timing of activities.

    Calorie Storage Depends On Meal Times
    It has been known for several decades that the composition of the initial meal of the day tends to set the body’s response to food intake later in the day. Not eating breakfast, for instance, tells the body that it should reduce energy expenditures and conserve in the face of famine conditions. Eating refined carbohydrates and sugars causes an insulin release that blocks fat metabolism, forces the body to rely on stored glycogen for energy and leads to energy peaks and valleys, the blood sugar “roller coaster.” Protein breakfasts including either fat or carbohydrates tend to even out energy levels and retain what is known as “metabolic flexibility,” the ability to harness either glucose or stored fat for fuel as needed.

    A good example of the meaning of meal timing in practice emerged recently in several trials using animal models. Mice and rats are extremely sensitive to the level of fat in their diets, in part because their natural diets are very low in fats. Unlike humans, both animals eat more or less continuously during their waking periods of activity. Either high- or low-fat diets spread throughout their normal 12-hour feeding period exercise limited effects on food intake and energy usage. Under these conditions, the animals generally adjust consumption and expenditure to maintain balance and metabolic parameters within normal ranges. Feeding a high-fat meal at the beginning of the feeding period does not alter metabolic flexibility and, again, the animals adjust. However, the same high fat meal taken at the end of the animals’ waking period leads to increased “weight gain, adiposity, glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia” independent of either total or fat-derived calories.3 The major surprise, one that runs counter to common assumptions, is this finding: “We report that high fat feeding at the transition from sleeping to waking appears to be critically important in enabling metabolic flexibility and adaptation to high carbohydrate meals presented at later time points. Conversely, high carbohydrate feeding at the beginning of the waking period dramatically impairs the metabolic plasticity required for responding appropriately to high fat meals presented at the end of the waking period.” In other words, the standard American breakfast of sweetened cereal or other refined carbohydrate products impairs the ability of the body to properly metabolize fats eaten later in the day.

    Other researchers have found similar results. Again in a mouse model, one group found that a diet sufficiently high in fat to induce weight gain and related changes if fed ad libitum did not lead to such changes if restricted to a limited feeding period.4 Not caloric restriction or fat restriction, but a restricted feeding period led to favorable results. “Timed restricted feeding provides a time cue and resets the circadian clock, leading to better health.” Simply put, a timed high-fat diet resets circadian metabolism and prevents obesity in this mouse model despite the high-fat content in an animal that normally consumes very little fat.

    What About Humans?
    A number of recent clinical experiments have confirmed the findings from these animal models as being applicable to humans, with increased protein consumption at breakfast proving to be especially helpful. For instance, in overweight/ obese, “breakfast-skipping” late-adolescent girls, breakfast, and especially a high protein breakfast led to better appetite control, better regulation of food intake and reduced evening snacking compared to not eating breakfast even though in this short study (one week) there was no change in total energy intake.5

    Another study, this one in overweight and obese adults, found that both a low-carbohydrate breakfast (not specifically high in protein) and a high-protein plus carbohydrate breakfast led to impressive weight loss over a period of 16 weeks (15.1±1.9kg and 13.5±2.3 kg, respectively) when followed in conjunction with reduced energy intake. After the diet ended, subjects were tracked for a further 16 weeks. As is found commonly in such models, there was significant weight regain in the lowcarbohydrate only breakfast group compared to the protein plus carbohydrate arm.6 This finding should surprise no one in that it is easier to add protein to more “normal” meal patterns than it is to radically reduce carbohydrates. Low-carbohydrate diets tend to lead to considerable rebound as dieters return to their normal eating habits. People who have increased their protein consumption along with changing other eating habits find it easier to continue some version of their new eating pattern.

    Yet another study, this one restricted to overweight and obese women, found that in a restricted calorie diet (~1,400 kcal) the results were significantly better at the end of 12 weeks in the women who ate a large breakfast (700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) as opposed to a large dinner (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner).7

    Eating breakfast, especially one that is higher in protein, has been found again and again to be superior to skipping breakfast or eating a breakfast built around carbohydrates. The shake out in meal composition revolves much more around the role of protein than fat because fats actually play a somewhat neutral role. As one paper’s title runs, “Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids.”8 The primary difference is that in those who are overweight or obese, as opposed to in individuals who are lean or normal weight, fat has less satiating power than does protein.9 Otherwise, as long as high-fat consumption is not a marker for generally poor eating and exercise habits (low consumption of fruits and vegetables, low consumption of fiber, high consumption of sugars and refined carbohydrates), fat consumption, after 60 years of controversy, has not been shown to be innately a threat to health.10 Just remember that the foods eaten at breakfast tend to determine the body’s ability to retain metabolic flexibility later in the day. Breakfasts that container significant fat do not tend to interfere with the ability to metabolize fat rather than store it later in the day, breakfasts built around carbohydrates do, and protein is the great equalizer.

    Conclusion
    Whether it concerns mice or men, the timing of meals is important. Eating more at breakfast and less at the evening meal leads to better appetite control and better metabolic functioning along with better weight control. Eating more protein and fewer carbohydrates at the morning meal, likewise, leads to greater metabolic flexibility later in the day. The standard American breakfast of cold, sweetened cereal is a very poor choice for control of appetite, energy levels or body weight. Fats are a largely neutral in this picture, although they certainly can replace a good portion of carbohydrates, especially if more protein is consumed. The old adage to “breakfast like a king, lunch like prince and sup like a pauper” turns out to be good advice. Best of all, changing the timing and size of meals is free!

    References
    1. Hernandez-Morante JJ, Gomez-Santos C, Milagro F, Campión J, Martínez JA, Zamora S, Garaulet M. Expression of cortisol metabolism-related genes shows circadian rhythmic patterns in human adipose tissue. Int J Obes (Lond). 2009 Apr;33(4):473–80.
    2. Dallman MF, Akana SF, Bhatnagar S, Bell ME, Strack AM. Bottomed out: metabolic significance of the circadian trough in glucocorticoid concentrations. Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl 2:S40–6.
    3. Bray MS, Tsai JY, Villegas-Montoya C, Boland BB, Blasier Z, Egbejimi O, Kueht M, Young ME. Time-of-day-dependent dietary fat consumption influences multiple cardiometabolic syndrome parameters in mice. Int J Obes (Lond). 2010 Nov;34(11):1589–98.
    4. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012 Jun 6;15(6):848–60.
    5. Leidy HJ, Ortinau LC, Douglas SM, Hoertel HA. Beneficial effects of a higher-protein breakfast on the appetitive, hormonal, and neural signals controlling energy intake regulation in overweight/obese, “breakfast-skipping,” late-adolescent girls. Am J Clin Nutr. 2013 Apr;97(4):677–88.
    6. Jakubowicz D, Froy O, Wainstein J, Boaz M. Meal timing and composition influence ghrelin levels, appetite scores and weight loss maintenance in overweight and obese adults. Steroids. 2012 Mar 10;77(4):323–31.
    7. Jakubowicz D, Barnea M, Wainstein J, Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring). 2013 Dec;21(12):2504–12.
    8. Luscombe-Marsh ND, Noakes M, Wittert GA, Keogh JB, Foster P, Clifton PM. Carbohydrate-restricted diets high in either monounsaturated fat or protein are equally effective at promoting fat loss and improving blood lipids. Am J Clin Nutr. 2005 Apr;81(4):762–72.
    9. Brennan IM, Luscombe-Marsh ND, Seimon RV, Otto B, Horowitz M, Wishart JM, Feinle-Bisset C. Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men. Am J Physiol Gastrointest Liver Physiol. 2012 Jul;303(1):G129–40.
    10. Schwingshack L, Hoffmann G. Comparison of effects of long-term low-fat vs high-fat diets on blood lipid levels in overweight or obese patients: a systematic review and metaanalysis. J Acad Nutr Diet. 2013 Dec;113(12):1640 – 61.
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