Melatonin, or N-acetyl-5-methoxytryptamine, as some scientists would say, is not just one out of several, it is the circadian hormone, per se. Being produced in the pineal gland, melatonin has been shown to reset, regulate and synchronize the internal clock of our bodies (Arendt. 1987).
In the late evening, when the sun sets and the production of melatonin is no longer suppressed by the light-induced negative feedback on the pineal gland, your natural melatonin production kicks in.
Unfortunately, next to artificial light, which is something you can easily avoid by wearing a blindfold in bed, aging (Karasek. 2004) and metabolic diseases incl. obesity (Reiter. 2012) will also inhibit the increase in serum melatonin in the hours before you go to bed.
Melatonin Supplements Are A Potential Fountain Of Youth
Studies have shown that the natural melatonin production starts to decline by the age of 30 – and that at a pace pretty rapid pace of approximately 2% per year (Sack. 1986). This decline in melatonin, which is still falsely considered to be a simple “sleep hormone” by many medical practitioners, goes hand in hand with a decline in antioxidant defenses. The same decline, of which researchers believe that it is at the heart of the anatomical and functional degeneration organs undergo during when we age. Accoringly, Reiter is spot on, when he points out in a 1994 paper in the peer-reviewed scientific journal Acta Neurobiologiae Experimentalis that the age-induced decline in melatonin production “may well play a significant role in aging processes,” and that its prevention (e.g. by supplementation) “could be prevented” or at least “[delay] the aging process” (Reiter. 1994).
The scientist from the University of Texas in San Antonio also believes that supplemental administration of melatonin may be beneficial in delaying age-related degenerative conditions, particularly in view of the fact that free radical damage has been implicated in a number of neurodegenerative disorders, which may be forestalled by chronic melatonin administration.
Melatonin and the prevention of neurodegenerative diseases
More recently, scientists from the Netherlands Institute for Brain Research supplied further evidence that Reiter’s 20-year old hypothesis may actually be true (Wu. 2005). In their paper in the Journal of Pineal Research, Ying-Hui Wu and Dick F. Swaab report that they were able to show that the disruption of melatonin production is a characteristic feature of Alzheimer’s that can be observed “as early as in the very first preclinical stages” (Wu. 2005) of this debilitating neurological disease. It is thus not surprising that early rodent data suggests that melatonin supplementation can reduce or even prevent both, the normal and pathological aging process of the brain and could thus help you to avoid a whole host of neurological problems we see in the elderly, today (Ramírez-Rodríguez. 2012; Peng. 2013). Many of these hypothetical benefits have already been confirmed for Alzheimer disease, Parkinson disease, Huntington’s disease and Amyotrophic Lateral Sclerosis (Polimeni. 2013).
Melatonin as a Zeitgeber and antioxidant
Whether the benefits are a mere result of the powerful antioxidant capacity of melatonin, of which scientists from the Atatürk University have shown that it they are 10x more pronounced than those of vitamin E (see Figure 1), is something researchers are still debating.
Figure 1: Percentage inhibition of lipid peroxidation by melatonin and
alpha-tocopherol in a linoleic acid emulsion as a marker of the potent
anti-oxidant activity of melatonin (Gulcin. 2002)
What stands out of questions, though, is the fact that at least part of the benefits of melatonin are mediated by its ability to synchronize and reset the central (brain) and peripheral (liver, muscle, fat, etc.) clocks of your body.
This is an important effect, since the loss of synchronicity of central and peripheral clocks has been associated with the whole spectrum of diseases of civilization ranging from “C” as in cancer to “O” as in obesity, almost all of the contemporarily increasing ailments is in one way or another related to the lack of synchronicity of the central and peripheral clocks in our brain and organs tissue.
No wonder, shift work, and even the chronic exposure to bright (specifically blue) light at night have been consistently linked to increased obesity and cancer risks in men and women (Hansen. 2002; Kubo. 2006; Viswanathan. 2007; Antunes. 2010).
The anti-obesity, pro-metabolic effects of melatonin supplements
Rodent studies show that the provision of melatonin supplements can realign the peripheral and central clock and prevent mammals from the negative side effects (Prunet-Marcassus. 2003). In their 2012 review of the literature, F. Nduhirabandi, E. F. du Toit and A. Lochner list 24 experimentally verified metabolic benefits of melatonin supplementation (see Figure 2 ).
Figure 2: Obesity related health parameters that may improve with melatonin treatment
In view of the fact that melatonin has also been implicated as a regulator and controller of brown, i.e. fat burning adipose tissue mass and activity, it is obvious that the pineal hormone is already touted as the most promising “naturally occurring substance with no reported toxicity” that “may serve as a novel approach for treatment of obesity” (Tan. 2011) by researchers all around the world (Bonnefont-Rousselot. 2014; Cipolla ‐ Neto. 2014).
Figure 3: Summary of metabolic and chronobiological actions of melatonin resulting in the regulation of energy metabolism, energy
balance, and ultimately body weight (left); and consequences of the absence or reduction in melatonin production (right; cf. Cipolla-Neto. 2004).
As Cipolla-Neto et al. explain in their review of the negative effects of a lack of melatonin, even the scope of the already known ill health effects is huge (see Figure 3 , right). The same can be said of the health benefits that may be achieved by its specific and well-timed supplementation:
While all of the previously listed benefits have been observed in rodent studies, the unwarranted fear that the use of melatonin supplements could have negative side effects, let alone shut down the natural melatonin production permanently is to blame that corresponding human trials are rare.
General antioxidant activity – Polish scientists found that the provision of 5mg of melatonin approximately 1h before bed for 30 days normalized the age-related decrease in erythrocyte anti-oxidant status and may thus “prolong the lifespan and improve the quality of life of elderly people.” (Kędziora ‐ Kornatowska. 2007). Similar beneficial anti-oxidant effects have been observed by the same researchers in hypertensive subjects and type II diabetics, as well (Kędziora ‐ Kornatowska. 2008; Kędziora ‐ Kornatowska. 2009).
Blood pressure control – In 1998, already, Cagnacci et al. reported significant improvements in artery blood flow, decreased blood pressure, and a reduces stress response in young, healthy women in response to the administration of 1 mg of melatonin. Similar effects have subsequently been reported by Arangio et al. (1999) in young men. More recently, scientists from the Netherlands Institute for Brain Research have been able to show similar benefits in response to chronic supplementation with 2.5mg of melatonin before bed. The supplementation regimen reduced the systolic and diastolic blood pressure in hypertensive men during sleep by 6 and 4 mm Hg, respectively (Scheer. 2004). Similar results have been reported by Ray et al. (2003) who observed that melatonin attenuates the sympathetic nerve responses to orthostatic stress in humans.
Cancer prevention and treatment – Blask et al. observed a rise in markers of tumor suppression in a human volunteer in response to a commercial 3mg preparation of melatonin (Blask. 2005).
Metabolic syndrome – Koziróg et al. (2011) report that comparatively small doses of 5mg/day (rodent studies often use 10mg or more) melatonin improve blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome.
Along with other studies, the previously cited experimental evidence has long convinced our the AgeForce R&D team of the great health benefits of melatonin supplements, which may be significantly augmented by the time-released delivery of melatonin through the skin.
Optimal NO levels will thus protect you from all the potentially fatal secondary diseases (heart disease, stroke, etc.) that have been associated with chronic hypertension (Haynes. 1993; Stamler. 1994).
Some scientists even go so far as to speculate that the natural increase in NO production that occurs with acute and chronic training (Jungersten. 1997) may be partly responsible for the well-known exercise-induced improvements of blood glucose management. The impaired NO production in diabetics, on the other hand, is part of the vicious cycle that makes it so difficult for diabetics to normalize their glucose levels and lose weight.
Nitric oxide is also heavily involved in the differentiation and regeneration of cells of our nervous system; and even though “the precise functions of NO in developing and regenerating neurons remain unclear” (Bredt. 1994), scientists know for sure that reduced nitric oxide levels as they occur with aging, diabetes and several other common ailments promote the progression of cognitive decline.
Men are yet not the only ones whose sexual function critically depends on the presence of sufficient levels of nitric oxide and its influence on the previously discussed production of serotonin and dopamine, as well as its direct impact on the production of fertility hormones via the NO-induced release of the luteinizing hormone releasing hormone aka “LHRH” (Mani. 1994).
Figure 3: The reformulated nitric oxide patch feeds into both pathways, the arginine
NO pathway (classic) and the nitrate NO pathway to maximally boost your NO levels.
By feeding directly and without first-pass in the liver into the “arginine > nitric oxide”- and the “nitrate > nitric oxide”-pathways, the reformulated “Nitric Oxide Booster” Patch induces significantly more pronounced increases in NO production than any of the first generation arginine-only products you may have tried.
Figure 4: 10-km time-trial performance of 10 trained cyclists with (A) individual data and
(B) mean power output after 6 days on either nitrate or placebo supplement (Cermak. 2012).
The corresponding increases in nitric oxide production are profound enough to trigger increases in performance not just in sedentary and moderately trained individuals (cf. Besco. 2012), but also in highly trained individuals whose NO production is naturally elevated (Jungersten. 1997; Cermak. 2012 | cf. Figure 4).
Studies show that every year, “losing weight” is the #1 New Year’s resolution (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:
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:
Figure 2: Brown adipose tissue volume and activity in 5 healthy men after sleeping at
room temperatures of 24°C, 19°C, 24°C and 27°C 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 19°C vs. 24°C, doing it constantly could, as Lee et al. point out, “open avenues to harnessing BAT for metabolic benefits” (Lee. 2014).
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).
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)
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…
…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 traveling.
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:
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.
As mentioned before, some of the protein in your diet may, and in case of those of you who work out, actually should come from protein supplements. 30g of whey protein consumed “right” (5-60min) after a workout, for example, will promote the protein anabolic response of exercise and help you maintain and build lean muscle mass, depending on whether you are dieting or in a maintenance / hyper caloric (=bulking) phase.
Now that you know what it takes to turn your life around, the last advice we can give you is to start today! What is keeping you from starting today? So go to the grocery store, buy fresh foods and make today the first day of your new leaner and healthier life!
Next to its well-known effects on cellular growth and repair, human growth hormone has been shown to have significant beneficial effects on protein synthesis, fatty acid oxidation and body composition.
Declines in growth hormone production affect us all
As early as in the 1960s, scientists discovered that the regular ups and downs of growth hormone are impaired in both obese and diabetic patients (Yalow. 1965).
Figure 1: The natural growth hormone production is significantly reduced with aging (Corpas. 1993)
Obesity and diabetes are yet not the only reasons for our growth hormone levels to drop. Studies have shown that with advancing age, even men and women with no clinical evidence of pituitary pathology develop significant decreases in GH secretion (Corpas. 1993). Against that background it is not surprising that growth hormone therapy is associated with significant improvements in several health-relevant parameters in the aging population:
The latest reviews clearly confirm these earlier studies and highlight that the therapeutic administration of human growth hormone will also prevent the age-induced decline in collagen expression in the musculotendinous tissue and effectively increase tendon and bone strength (Boesen. 2014).
The number of young(er) individuals with suboptimal growth hormone levels increases
Only recently, researchers from the Cedars-Sinai Medical Center observed that there is a growing number of people being diagnosed with what scientists and doctors call “idiopathic GH deficiency in adults” (Melmed. 2013) – a condition, that is characterized by chronically suppressed growth hormone levels in the absence of pathological triggers or external cause of growth hormone deficiency
Just like older individuals, young people who suffer from idiopathic growth hormone deficiency exhibit somatic changes in body composition, total energy expenditure and fatty acid metabolism that occur in response to the absence of adequate growth hormone levels. Changes that are, just as it is the case in older individuals reversible by the means therapeutic growth hormone supplementation. e treatment as it is now available to everyone with AgeForce’s unique transdermal growth hormone patches.
Over the past decade, the list of scientifically confirmed benefits of growth hormone therapy has expanded. As of now, the following benefits have been scientifically confirmed (Carroll. 1998):
While previous research focused almost completely on physiological benefits, the psychological and cognitive benefits of growth hormone therapy have gained more and more attention within the scientific community over the past decade. Van Dam et al. highlight that
“[…b]ased on the available data, one might hypothesize that relative GH or IGF-I deficiency could contribute to the deterioration of cognitive functions observed in the elderly.” (Van Dam. 2000)
Due to the complex interactions between human growth hormone and the neuro-endocrine axis, experts expect to find further neurological benefits in future trials. Only recenty, Nyberg & Halberg speculated that growth hormone “might interact with specific receptors located in areas of the CNS that are associated with the functional anatomy of these behaviours” (Nyberg. 2013) and thus contribute directly to increases in synaptic plasticity and human cognitive capacity in people with and without growth hormone deficiency.