Phase4 Pharmaceutical - AgeForce R&D Div.

Studies show that every year, "losing weight" is the #1 New Year's resolution (Kassirer. 1998).

• "They buy low-calorie and low-fat foods, deny themselves desserts, drink only artificially sweetened beverages, join commercial weight-loss clubs (and buy their special and especially expensive prepared meals), visit fat farms, take diet pills of one sort or another, submit to liposuction, and exercise obsessively to burn calories. Every new remedy is greeted with a wave of enthusiasm, from amphetamines and thyroxine in the 1960s to Olestra, fenfluramine and phentermine (fenphen), and sibutramine in the 1990s. The goal is to reach the elusive American ideal to be slim, fit, and forever young" (Kassirer. 1998).

Does what Kassirer et al. describe in their 1998 article sound remotely familiar? If so, this research paper is for you, assuming you have the desire and the discipline!

99% Of The People Who Make New Year's Resolutions Make One That that Includes Losing Weight

"Expend more energy than you consume!" That sounds easy. Unfortunately, the "calories in" vs. "calories out" equation has more than the often-cited two parameters intake and expenditure. And due to the subtle, yet complex ways by which energy intake and energy expenditure directly and indirectly influence each other, losing weight is much harder than any of the shiny articles in the men's and women's magazines would suggest.

We want to be honest with you: Those of you, who have acquired a significant amount of unwanted body fat, are usually not going to be able to achieve ambitious weight loss goals within one year. Against that background it is important that you realize that a "new year's resolution" is not going to suffice.

Make Your New Year's Resolution a New Life's Resolution!

Rather than with a new year's resolution, your next and last weight loss program should thus start with a "new life's resolution". And one thing cannot be debated: Unless you are not willing to make an ongoing commitment, you are not going to shed that belly and keep it off for the rest of your life. Shocking?

OK, with that being said, let's see what Ongoing commitment, desire, and discipline entails:

#1 Stick to regular sleeping habits and get 6-8 hours of sleep every night!

Studies show significant correlations between obesity and a lack of sleep or, to be even more precise, a lack of regular sleep patterns (Penev. 2014; Coughlin. 2014). 7-8h per night and being in bed at a fixed time that does not change from one day to another is thus what you should aim for in the future - and that's not just because this may decrease your appetite reduce your desire for sweet and salty junk foods by (62% | Tasali. 2014), but also because your life could depend on it, as the significantly increased mortality risk in show.

Figure 1: A 2009 meta-analysis indicates that sleeping less than 7h per night has repeatedly been shown
to be associated with up to 100% increased mortality risk (Gallicchio. 2006).

For many of us sticking to regular sleep patterns can be hard, though; and that is not just, because it requires not hanging out in front of the television for hours. To help you stick to your new sleeping routine we have thus compiled a list of tips:

• Rituals, like brushing your teeth 10 minutes before you go to bed, or changing into your pajama will help you to stick to the routine.

• Sleeping in a pitch-dark room and using earplugs will help you to improve your sleep quality.

• Having a low temperature in your sleeping room 19 C and a blanket are optimal according to sleep experts. A recent study from the National Institute of Diabetes and Digestive and Kidney Diseases even indicates that sleeping in cold bedroom can even improve your glucose metabolism and increase the amount and activity of metabolically active brown fat in your body and may thus help you lose weight in the long(er) run (Lee. 2014).

Figure 2: Brown adipose tissue volume and activity in 5 healthy men after sleeping at
room temperatures of 24C, 19C, 24C and 27C for one month, each,
consecutively respectively (Lee. 2014)

And while the increase in BAT volume and activity returns to normal level after one months of sleeping at 19C vs. 24C, doing it constantly could, as Lee et al. point out, "open avenues to harnessing BAT for metabolic benefits" (Lee. 2014).

If all these tips still do not help, you can still use one of our melatonin patches before. The AgeForce Melatonin patches will help you maintain an optimal circadian rhythm and restore the circadian rhythmicity the day after a night, where you have failed to stick to your regular sleeping pattern.

#2 Get off the couch and take the 10,000+ steps a day approach to a leaner self

Table 1: A blueprint for standard and advanced training routines

You do not have to become a marathoner or start every day with a 10-mile jog. If you have been a lazy couch potato for at least 10 years, start by using a step-counter. Make sure you get in at least 10,000 steps a day. If you fail your goal on two days in a row, make up for the missing steps by an extended walk in the park.

While being more active, taking the stairs and walking to the office, instead of taking the bus are important, doing all that is not enough to develop the physique most of us are dreaming of. The logical next step is thus to embark on a workout program with three workout days for beginners and five workout days for advanced trainees.

Both routines require less than 1h of your time on three or five days of the week and are designed to promote the reduction of body fat while maintaining or even increasing the amount of lean mass.

The conservation and / or increase of lean mass makes the difference between short-term, non-sustainable weight loss that leaves you lighter, but not sexier or healthier, and long-term, sustainable fat loss that leaves you lighter, sexier and healthier for both men and women (Ravussin. 1988; Stiegler. 2006). The incorporation of strength training into your weight loss routine is thus not facilitative. It is obligatory.

The same goes for high intensity interval training (HIIT), of which numerous of studies have shown that it will ramp up your metabolism, improve your glucose management and promote fat over simple weight loss in both, lean and obese individuals (Buchhei. 2013; Sloth. 2013; Karstoft. 2013). In addition, working out intensely (resistance training and HIIT) has another important advantage: High intensity exercise like running curbs the cravings and reduces the energy intake of the trainees compared to low-to-moderate intensity exercise.

Figure 3: Effects of exercise duration and intensity on energy intake; exemplary study results from Larson-Meyer et al. (2012) While both, high intensity exercise (running) and low intensity exercise (walking) will expend additional energy (EE), the latter induces an increase in energy intake (AEI) that is larger than the amount of energy that was expended during the walk.

As the data from Larson Meyer et al. (2012 | see Figure 3, right) indicates, running will thus effectively reduce the energy balance (REI) by 193kcal, while walking, despite increasing the energy expenditure by 333.83kcal will increase the post-workout ad-libitum energy intake to an extend that will completely negate the benefits. Specifically for those of you who are still huffing and puffing like crazy during the HIIT session on Monday (3-Day Protocol) the steady state cardio session on Friday will be a highly effective tool to improve their overall conditioning and to give their body a change to burn the circulating free fatty acids and triglycerides. In fact, a 2014 study by Keating indicates that obese individuals will see greater changes in body composition with steady state vs. high intensity interval training (Keating. 2014).

And even for those of you who are lean and fit already, there may be some room for steady state "classic" cardio training in your regimen. You should be aware though that HIIT is the more time-efficient fat burning exercise; and that it has the important advantage of being scalable even for the fittest of you. In contrast to steady state cardio, where you cannot increase the duration and/or intensity infinitely, there is always room for pedaling faster and/or doing a another interval with HIIT training without running the risk of running yourself into the ground (literally).

#3 Don't "diet"! Change your diet forever!

Now a lack of exercise is one thing, the most common reason people do not achieve their weight loss goals however is a different one: It is "dieting". This may sound absurd at first, but the whole concept of "going on a certain diet" to lose weight temporarily is intrinsically flawed, because it implies that you would be allowed to go back to your previous eating habits, when the unwanted extra-weight is lost. This, however, is not going to happen... unless you want to ruin your results and end up fatter and unhealthier than before.

In fact, Successful dieters usually do not change their energy intake drastically. They determine their baseline requirements by tracking their overall energy intake for two weeks and reduce the number of kcal they consume on a daily basis by 25%-30%. So, if you have counted calories for two weeks ending up at an intake of 28,321 kcal (total), your average daily energy intake before the switch is 2022.93 kcal/day and your new target intake would be 75% of that, i.e. 1517.2 kcal/day.

Do not trust any of the thousands of quacks on the Internet who will be telling you that you do not have to cut your energy intake to lose weight.

Even if you are following a ketogenic diet, the weight loss will not occur magically and without a reduction in energy intake. A reduction which is, in case of this particular high fat diet, induced by a general decrease in appetite and, more importantly for most dieters, the inability to eat all those foods that have previously been promoting the unconscious overconsumption of energy like cookies, candy, pies, pizza, fries, burgers, etc. The same overconsumption of energy that is responsible for the unwanted belly fat you see, when you are trying to look at your feet.

Figure 4: Even in obese subjects a moderate energy restriction (-30%) is more effective than a severe one, because the amount of body fat that's lost per calorie you don't eat is higher and the nitrogen and consequently, the lean mass loss is reduced (Sweeney, 1993)

Consume a whole foods diet with a high amount of protein and the right macronutrient composition for your current weight status and activity level

This does not mean, though, that how much you eat was the only thing that counts. On the contrary, what you eat does matter! It does of course make a difference if you are living on Twinkies and Dingdongs all day or eating a whole-foods diet with a relatively high content of high quality protein sources like lean meats, chicken, fish, dairy, eggs and if you want to protein powders. At the same energy intakes, the latter will have you lose more fat and less muscle than the Twinkies + Multivitamin supplement diet Mark Haub used to lose 27 pounds back in 2010.

Now, "high protein" does not mean that 50% or even more of your energy intake should come from protein, but it does mean that each of the meals you consume should contain 30-40g of high quality protein, i.e. protein with a high amount of essential amino acids, such as fish, meat, dairy, eggs, soy, chicken, etc. By sticking to this rule of thumb and consuming three square meals a day, you will be able to fix your average protein intake at a minimum of 90-120g per day and to...

• Increase the satiety response to each of the meals you consume,

• Improve the post-prandial glucose utilization,

• Raise the postprandial increase in resting energy expenditure, and

• Trigger an increase in protein synthesis,

• Help conserve muscle mass while you are dieting,

...Furthermore the "30-40g rule" will give you some orientation in terms of which foods to eat and how to combine them.

What about fasting? It depends on your ability to use fatty acids as fuel, whether or not you are going to benefit from intermittent or alternate day fasting. If you want to give it a try, there are two variants of fasting you should keep in mind: (1) Intermittent fasting, where you usually skip breakfast (+optimally lunch) and follow a 18h fasting, 6h feasting diet, as well as (2) alternate day fasting, where you eat ad-libitum (=as much as you want, while keeping an eye on not pigging out) on one day and stick to 800kcal with at least 100g protein (total) in three square meals on the other day. Both can work, but there is still a paucity of evidence that would confirm that intermittent fasting or alternate day fasting are necessarily superior to "regular" dieting.

A meal that consists of nothing else but salad leaves with a surprisingly high carbohydrate + high fat "yogurt dressing", for example, is a "no-go" for anyone following this simple rule of thumb. Buying the same salad with a simple vinaigrette dressing (vinegar + oil) and adding a can of tuna on top, however, would be a good and easily obtainable lunch for anyone who has no access to quality foods at work or while travelling.

Figure 5: Overview of possible dietary macronutrient compositions for sedentary obese,
slightly chubby, active and athletic, active individuals (please read the text for elaborations).

Another thing to take into consideration with every meal you consume is the macronutrient distribution. For the sedentary obese person, who may suffer from chronic inflammation and diabetes, as well, it is best to cut out carbohydrates completely, until he has lost enough weight to qualify as "overweight" and / or takes up an intense exercise regimen.

The ketogenic diet is thus a "diet" in the classic sense. When a certain amount of weight is lost and a certain degree of regular physical activity is reached, the formerly obese person would reintroduce carbohydrates into his / her diet, while increasing the intake of satiating, muscle building protein. For the slightly chubby, but active and the athletic, active individual, the dietary composition is thus given in form of threshold values and the recommendation to satisfy the rest of his / her daily energy requirements with carbohydrates. How does that work? Let's consider the following two examples:

Who	Obese, sedentary man	Chubby, active woman	Athletic, active man
Daily kcal goal	2000kcal	1,750kcal/day	3,000kcal/day
Body weight	210kg	70kg	90kg
Protein	60g	105g	198g
Fat	188g	90g	120g
Carbohydrates	15g	130g	282g

Table 2: Example of how the recommendations in figure would turn out for three different individuals

You should be aware though that the above recommendations are nothing, but a rule of thumb. Some people may function better on high fat, low carbohydrate diets, even when they are already lean and highly active. For the majority of people, switching back to a "regular" diet that does not exclude any of the three main macronutrients is yet the more practical and more sustainable solution. If that does not work for you, experiment with different macronutrient ratios.

#4 Take supplements but choose wisely!

Our recently reformulated Fat Burning Weight Loss patch, with our latest formula upgrade, will help you to keep your appetite in check. It will boost your metabolism and thus produce the same results on a small energy deficit you would otherwise see, only if you starve yourself; and most importantly the new formula, which contains hoodia, higenamine and yohimbine, will ensure that the weight you lose is fat and fat, only! In that, the addition of yohimbine will help you to finally tap into the stubborn deep abdominal fat around the abs (for men) and on the buttocks (for women).

#5 Start today, not on New Year's Eve!

Now that you know what it takes to really lose weight and keep it off, the last advice we can give you is to start today! So go to the grocery store, buy fresh foods, start exercising and, or working out, and be sure to order your Fat Burning Weight loss patches for your new leaner and healthier life!

References:

Buchheit, Martin, and Paul B. Laursen. "High-intensity interval training, solutions to the programming puzzle." Sports medicine 43.5 (2013): 313-338.

Coughlin, Janelle W., and Michael T. Smith. "Sleep, obesity, and weight loss in adults: Is there a rationale for providing sleep interventions in the treatment of obesity?" International Review of Psychiatry 26.2 (2014): 177-188.

Gallicchio, Lisa, and Bindu Kalesan. "Sleep duration and mortality: a systematic review and meta‐analysis." Journal of sleep research 18.2 (2009): 148-158.

Karstoft, Kristian, et al. "The Effects of Free-Living Interval-Walking Training on Glycemic Control, Body Composition, and Physical Fitness in Type 2 Diabetic Patients A randomized, controlled trial." Diabetes care 36.2 (2013): 228-236.

Kassirer, Jerome P., and Marcia Angell. "Losing weight--an ill-fated New Year's resolution." The New England Journal of Medicine 338.1 (1998): 52.

Keating, Shelley E., et al. "Continuous Exercise but Not High Intensity Interval Training Improves Fat Distribution in Overweight Adults." Journal of obesity 2014 (2014).

Lee, Paul, et al. "Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans." Diabetes (2014): DB_140513.

Penev, Plamen D. "Shortened Sleep Time and Obesity." Treatment of the Obese Patient. Springer New York, 2014. 113-120.

Ravussin, Eric, et al. "Reduced rate of energy expenditure as a risk factor for body-weight gain." New England Journal of Medicine 318.8 (1988): 467-472.

Sloth, Martin, et al. "Effects of sprint interval training on VO2max and aerobic exercise performance: A systematic review and meta‐analysis." Scandinavian journal of medicine & science in sports 23.6 (2013): e341-e352.

Stiegler, Petra, and Adam Cunliffe. "The role of diet and exercise for the maintenance of fat-free mass and resting metabolic rate during weight loss." Sports Medicine 36.3 (2006): 239-262.