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Fat Loss

Fat loss is the breaking down of stored fatty acids into usable energy, thus leading to the shrinkage and depletion of adipocytes (fat cells). Lipolysis, or the breaking down of lipids (fats) is a highly regulated process that involves many hormones, signaling molecules, and facilitators. Some factors that promote the breakdown of fat into usable energy are hormones like epinephrine and glucagon and low levels of insulin, meaning the body is low on glucose and requires an energy source.

It is typically known that a caloric deficit is needed to reduce body fat. A caloric deficit means your body is spending more energy than it is consuming. This can trigger epinephrine and cortisol release, lower insulin levels, and subsequently cause the breakdown of fats into energy so that our body can remain functional.

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The Circadian Clock and Metabolism

The circadian rhythm is a complex system influenced by external and internal mechanisms. To ensure every cell in our body is properly tuned, an internal biological clock regulates various physiological processes in a 24-hour cycle.

The circadian clock is regulated by a series of genes and proteins that interact in a complex feedback loop. The most prominent genes involved in the circadian clock are the Period (Per), Cryptochrome (Cry), Brain and Muscle ARNT-like 1 (BMAL1), and Circadian Locomotor Output Cycles Kaput (CLOCK).

BMAL1 and CLOCK form a heterodimer complex that activates the transcription of Per and Cry genes. Once synthesized, Per and Cry proteins form a complex that inhibits the activity of BMAL1 and CLOCK, creating a negative feedback loop that regulates the expression of circadian genes. This feedback loop generates a 24-hour cycle of gene expression that regulates the body’s physiological processes.

Recently, it was found that skeletal muscle metabolism is influenced in some parts by the time-of-day.

The day is often split into rest and active phase. Note here that mice are active during the night, in contrast to humans being active during the day. Nonetheless, exercise during each phase has different effects on skeletal muscle metabolism, whereas the effects of exercise timing on adipose tissue metabolism have not been studied extensively until now.

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Exercise Timing and Adipocyte Metabolism

Our cells depend on the circadian clock, regulated by a transcription-translation feedback mechanism. This clock can be manipulated in part by external stressors like diet and exercise. To truly optimize the benefits of exercise, we can align our physical exercise with our circadian clock. Recent research has concluded that while exercise at different phases does not significantly affect circadian clock genes, exercise does impact metabolism in adipose tissue. Exercise taking place in the early active phase, but not during the rest phase, resulted in a significant increase in serum non-esterified fatty acids (NEFAs). The increase in NEFAs is a powerful indicator of lipolysis, suggesting that exercise during the early active phase significantly increases lipolysis (break down of fats).

The authors also analyzed subcutaneous adipose tissue and found that there was a time-dependent change in exercise response. Some of these changes included activated steroid hormone receptors, glucocorticoid receptors, DNA binding transcription factors, and the fibronectin binding pathway.

To further show that exercise-timing was the correct variable responsible for this increase in lipolysis, the authors controlled for catecholamine levels and feeding status. Both variables did not significantly alter the effect of early active phase exercise on lipolysis, leading the researches to conclude that early active phase exercise can lead to enhanced lipolysis.

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Extrapolation

The data from this research suggest that early active phase exercise can enhance weight loss and possibly help combat obesity and type 2 diabetes. Although the research was performed on mice and the authors explicitly mentioned further investigation regarding the impact of exercise timing on diabetes is required, it may be beneficial to move some of your physical exercise to the early morning.

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Human Data and Conclusions

A human trial conducted in 2019 concluded that despite minimal differences in components in energy homeostasis, participants in the early morning exercise group lost significantly more weight than the late exercise group. While there are lots of variables in this trial, this trend goes hand in hand with the preclinical data discussed earlier.

Although there is promising data suggesting weight loss can be enhanced by exercising in the morning, other studies have shown sex-dependent effects on exercise-timing. Other smaller studies have shown that other factors like sleep quality and blood pressure can be altered by exercising at different times. Altogether, be sure to match your goals with the timing of your workouts and be on the lookout for new trials with larger sample sizes investigating the importance of exercise-timing on our health and fitness goals.

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References

1. https://www.webmd.com/fitness-exercise/news/20220620/best-time-of-day-to-exercise-goals
2. https://www.pnas.org/doi/pdf/10.1073/pnas.2218510120
3. https://www.nature.com/articles/s41598-023-31082-0#Sec2
4. https://www.nature.com/articles/s41366-019-0409-x

Review #12: The Negative Impact of Chronic Stress on Our Health and Easy Ways to Beat it

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Acute vs Chronic Stress

I bet you have been stung by a bee, or been jump scared at a haunted house, or even had your heart sink because you forgot to do that homework assignment. Yes, we have all been there and felt our hands shake, our breathing intensify, and our heart rate increase. These signs are typical in an acute stress response, a response only meaning to last a few minutes, often referred to as the “fight or flight” response. Our body goes from a parasympathetic state into a sympathetic state because of a stimulus that has triggered the release of epinephrine (or norepinephrine), sometimes called adrenaline (or noradrenaline). Epinephrine binds to receptors expressed on target cells and triggers a change in gene expression and cell signaling. With this rapid release of epinephrine, you have rapidly geared up for combat, now ready to run or fight to the utmost of your ability.

Another part of our stress response is much more subtle, and a disguised culprit, named “chronic stress”. This chronic stress can arise from many sources. Some of which include obesity-induced inflammation, type 2 diabetes, anxiety, psychological, and intestinal permeability. This chronic stress can cause hypercortisolemia. The high or slightly elevated levels of cortisol can cause a weakened immune system fatigue, stunt growth, and increase systemic inflammation. Several studies have found that people who report high levels of chronic stress have an increased risk of dying from cardiovascular disease. For example, a large-scale study of middle-aged men and women found that those who reported high levels of work-related stress were more likely to die from cardiovascular disease over a 14-year period than those who reported low levels of stress.

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Evolutionary Advantage of Cortisol

You might think that the release of epinephrine is the more ancient of the stress responses. After all, that spike in epinephrine hits like a truck and can make for some great athleticism. Despite logic, it is actually cortisol that is evolutionarily older. While our ancient ancestors and other mammals were running from predators, evolution selected for a longer acting stress signal. After all, the acute epinephrine response is exhausting and requires lots of energy, and you wouldn’t want to get too relaxed too quickly.

This evolutionary advantage of cortisol may have been useful in our nomadic ancestors, but as we domesticated and became more of a stationary body, the long-acting stress response can be detrimental to our health if it goes unchecked. Don’t get me wrong, cortisol is great. It prevents us from going hypoglycemic in times of exercise and can suppress the immune system in a stressful time. These things are useful today, but the perpetual release of cortisol from anxiety and other stressors can be extremely detrimental.

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Easy Ways to Lower Cortisol

1. Eat a nutrient rich diet
   • The lack of macro- and micronutrients can cause your cells sending stress chemicals, thus increasing cortisol release. Eating enough calories and nutrients is a sure way to reduce stress,
2. Meditation
   • Published research has showed that meditation can significantly reduce saliva cortisol levels, thus reducing stress.
3. Sleep
   • Getting enough sleep is crucial. Sleep is crucial for proper hormone balance, growth, and repair. Without proper repair, your cells release chemicals, triggering a stress response.
4. Family and Friends
   • Social life plays a vital role in your well-being. Being alone too often can cause depressive thinking and cortisol release. This method of reducing stress is highly variable, so be sure to find an appropriate amount of time to spend with family and friends that doesn’t negatively affect your alone time.
5. Exercise
   • Exercise can help to reduce stress and lower cortisol levels. Aim for at least 30 minutes of moderate exercise, such as brisk walking or cycling, most days of the week.

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The Importance of Magnesium

Magnesium is one of Earth’s most abundant elements, with each of us containing about 25g of magnesium in our bodies. 90% of that magnesium is found in muscle and bone tissue, where it plays a vital role in over 300 enzymatic reactions. Some of these reactions include stabilizing ATP, a major player in energy metabolism, DNA and RNA synthesis, and it plays a role in maintaining cellular ionic gradients.

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Magnesium Intake

The recommended daily intake of magnesium is 400-420mg/day for males and 310-320mg/day for females, yet over 20% of the youth in the United States are not reaching this RDI value. During puberty, many changes happen, stimulating bone and muscle growth, meaning micronutrient intake needs to be sufficient. In Taiwan, men and women were consuming only 68%–70% of the recommended dietary reference intake of magnesium.

The recommended dietary intakes (RDIs) for magnesium, like for other nutrients, are established by a group of independent experts called the Food and Nutrition Board (FNB) of the National Academy of Medicine in the United States. However, these values seem to be relatively static and new research is showing the need for higher RDIs for specific nutrients such as magnesium. New research in nutrition found that a daily intake of magnesium at 550mg had better brain health and could lower the risk of dementia.

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Magnesium and Dementia

The link between magnesium and dementia may seem hard to imagine. I mean, how can a simple element contribute to such a horrible and complex disease? Well, earlier research has found that magnesium in the brain plays a crucial role in maintaining neuronal health by limiting oxidative stress, enhancing synaptic plasticity, and lowering neuroinflammation. These findings have led researchers to investigate magnesium levels in a variety of neurodegenerative diseases, metabolic diseases, and cancers. However, nutrition research is quite daunting as it is hard to account for multiple variables and it is hard to get adequate funding for a proper testing scenario. Both together have made nutrition research very controversial and often nonreproducible.

Despite the pitfalls of nutrition research, this article published in the “European Journal of Nutrition” had over 500,000 participants and had quantifiable measurements like blood pressure, gray matter, and white matter lesions.

Overall, the study found that magnesium did not significantly affect blood pressure but did positively impact brain volume. In particular, the authors concluded that magnesium intake upwards of 550mg per day was associated with larger brain volumes and lower white matter lesions. Together, this data shows magnesium intake is higher than the RDI, resulted in a healthier brain compared to participants consuming less magnesium.

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Increase your Magnesium Intake

This is not the only research that supports taking magnesium at ~500mg per day. In fact, several studies have found similar results, albeit with much less evidence. To hear that you should increase your magnesium intake is one thing, but getting enough in your diet is another. The easiest way to go about this is to supplement with magnesium threonate/glycinate, start with 50mg per day and slowly titrate up to your desired dose. If you are not the supplement kind and want to find dietary sources of magnesium, start by incorporating pumpkin seeds, chia seeds, and almonds into your diet.

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What are Migraines?

A migraine is a type of headache that is typically characterized by a severe throbbing or pulsating pain on one or both sides of the head. Migraines can last for hours to days and can be accompanied by other symptoms, such as sensitivity to light, sound, and smells, nausea, vomiting, and fatigue. Migraines can significantly affect a person’s quality of life and productivity.

Migraines are a neurological condition that can be triggered by a variety of factors, including stress, hormonal changes, certain foods, and environmental factors. The exact cause of migraines is not well understood, but it is thought to involve a combination of genetic, environmental, and neurological factors.

There are different types of migraines, including migraines with aura and migraines without aura. Auras are sensory disturbances that can occur before or during a migraine, such as visual disturbances or tingling sensations in the face or hands.

Treatment for migraines typically involves a combination of lifestyle changes, medication, and alternative therapies. Over-the-counter pain relievers such as ibuprofen and acetaminophen can be used for mild-to-moderate migraines, while prescription medications such as triptans and ergotamines are often used for more severe migraines.

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Over-the-Counter Treatments

Migraines are a common neurological condition, and it is estimated that approximately 1 billion people worldwide suffer from migraines. Of those, about 10% experience severe migraines, which are defined as migraines that significantly affect a person’s ability to carry out their daily activities. Women are more likely than men to suffer from migraines, and migraines often start in adolescence or young adulthood. While severe migraines are often treated with prescription medications, mild-to-moderate migraine relief is centered on OTC medications like Excedrin, ibuprofen, or acetaminophen.

These OTC medications are considered relatively safe at recommended doses and dosing intervals but carry significant risks and do not prevent the onset of migraines. Therefore, the need to find safe and preventative compounds is of upmost important.

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Supplements and Migraine Relief

While the pathophysiology of migraines is poorly understood, it is believed that neuroinflammation, proinflammatory cytokine signaling, and mitochondrial dysfunction may be at play. Few studies have been published on using supplements to relieve migraines, but these compounds have some proof of efficacy and are all considered safe. These supplements include coenzyme Q10 (CoQ10), magnesium, and vitamin B2.

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Coenzyme Q10

CoQ10 is a naturally occurring compound found in the body that plays a critical role in energy production within cells. The mechanism of action of CoQ10 is related to its function as a coenzyme in the production of ATP (adenosine triphosphate), which is the primary source of energy for cells. CoQ10 is involved in the electron transport chain, a series of chemical reactions that occur within mitochondria, the energy-producing organelles within cells. In this process, CoQ10 helps to transfer electrons from one enzyme to another, ultimately leading to the production of ATP. By understanding its mechanism, we can see that CoQ10 supplementation targets energy metabolism and mitochondrial function in the pathway of preventing migraines.

Several studies have tested the efficacy of CoQ10 on the severity and frequency of migraines and have found that 150mg significantly reduced the severity and frequency of migraines.

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Vitamin B2

Vitamin B2, also known as riboflavin, is a naturally occurring compound found in lots of food we eat. It is involved in the metabolism of carbohydrates, fats, and proteins, and plays a key role in the production of energy within cells. The mechanism of action of vitamin B2 involves its function as a cofactor for several important enzymes involved in these metabolic processes.

It was found that a supraphysiological dose of vitamin B2 (400mg) reduced the frequency of migraines by nearly 50%. While large population studies have not been performed, this compound is considered well-tolerated and safe, making it a useful supplement for migraine prevention.

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Magnesium

Magnesium is an important element in our diet. Often, even when supplemented, the recommended intake is far from efficacious. Along with many reports that support magnesium as a supplement for reducing the frequency of migraines, recent research has concluded a daily intake of magnesium at 550mg could reduce the risk for certain neurodegenerative disorders.

When choosing a magnesium supplement, it is important to consider its bioavailability. For example, magnesium oxide is found in non-stimulant laxatives because it is poorly absorbed into the bloodstream and draws water into the intestines, thus promoting a bowel movement. Some of the most bioavailable forms of magnesium are magnesium glycinate and magnesium threonate. It should also be noted that your supplemental intake should consider your dietary intake from foods, etc.

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Conclusions

Migraines can be a daunting eventing to deal with, often leaving you with a half productive day and in a miserable haze. Prescription medicine is riddled with side effects and offers relief after migraine onset, but does not aid in preventing the occurrence of migraines. Some supplements, such as magnesium, coenzyme Q10, and vitamin B2, have shown therapeutic promise in many studies and have limited-to-no side effects. Before starting a supplement protocol, be sure to perform your own research, track your intake of nutrients, and, if necessary, ask a specialist for help.

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General Cell Biology

Our cells are powerful bodies with what seem to be a low-level intelligence. These little bodies contain a cell membrane, which separates the extracellular space from the intracellular space, which allows the cell to maintain certain concentrations of different molecules without them diffusing away from the cellular machinery. There are organelles within the cell. These are like organs in our body. The kidneys filter our blood, the heart pumps our blood, and the lungs removing waste and bring in oxygen. These lower-level groups of tissues, put together, constitute an organism. Some organelles include the endoplasmic reticulum for calcium storage, the Golgi body for processing lipids and proteins, the nucleus for safeguarding DNA, and ribosomes for synthesizing proteins. Put together, these organelles make up the cell.

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Energy in the Cell

In many chemical reactions, energy input is required for the reaction to occur. This energy input is necessary to break the chemical bonds of the reactants, which then allows new bonds to form to create the desired products. The amount of energy required to initiate a reaction is known as the activation energy. This activation energy can come from a variety of sources, including heat, light, and can be lowered by enzymes. Once the reaction has started and the activation energy has been supplied, the reaction can proceed on its own, releasing energy as heat or light. Some reactions, such as endothermic reactions, require a continuous input of energy to proceed, while others, such as exothermic reactions, release energy as they proceed. The amount and type of energy required for a reaction to occur depends on the specific reaction and the properties of the reactants involved.

If we zoom out from the chemist’s point-of-view, many biological processes require energy input. The most common energy “currency” in our biological system is adenosine triphosphate (ATP). When the gamma or beta-phosphate is hydrolyzed, energy is released, thus providing energy to reactions that require it.

Energy Production

Taking a step back, we can see that ATP is a source of potential energy for cellular reactions. But how do our cells get ATP? Well, making ATP requires energy input and can occur through two main pathways, substrate-level and oxidative phosphorylation. Phosphorylation is just adding a phosphate group to an existing molecule.

Substrate-level phosphorylation occurs during glycolysis, the breaking down of sugar, and the citric acid cycle. In both instances, a molecule that contains a phosphate group undergoes a reaction in which that phosphate group is directly transferred onto ADP (adenosine diphosphate) to make ATP.

Substrate-level phosphorylation only accounts for about 5% of total ATP production, which means the remaining 95% of ATP comes from oxidative phosphorylation. Oxidative phosphorylation occurs in the inner mitochondrial matrix and shuttles electrons through a chain of complexes, altogether called the electron transport chain (ETC). This creates a proton gradient, in which diffusion of the proton through ATP synthase (enzyme that makes ATP) results in ATP production.

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Mitochondrial Function

Just like a computer infected with a virus, a car without oil, or a phone in low-battery mode, your mitochondria function declines with increased stress, protein availability, and oxidative damage. This decline in mitochondrial function can lead to less efficient ATP synthesis and an increase in reactive oxygen species (ROS) which can lead to DNA damage. This decline in mitochondrial function can come from a recent illness, chronic/acute stress, aging, or a plethora of reasons, including circadian dysregulation.

To combat this decline in mitochondrial function or to optimize ATP synthesis, a variety of compounds can be used. We will break down the roles of each compound individually as it relates to mitochondrial function or ATP synthesis.

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Compounds for Supporting Mitochondrial Function

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Alpha Lipoic Acid

Alpha lipoic acid (ALA) has been shown to upregulate mitochondrial biogenesis, the process by which cells increase the number and size of their mitochondria. This can enhance mitochondrial function and energy metabolism, and has been proposed as a potential strategy to improve mitochondrial function. Furthermore, ALA demonstrated anti-oxidant activity, thus protecting the mitochondria from oxidative damage.

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L-Carnitine L-Tartrate

Carnitine increases the transport of fatty acids into the mitochondria, thus increasing ATP production, not through improving mitochondrial function but by optimizing its ability to use fatty acids.

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Coenzyme Q-10

Coenzyme Q-10 (CoQ10) is involved in the ETC, the key process that generates ATP in the mitochondria. CoQ10 is required for transferring electrons from complex I and II to complex III in the ETC, which is critical for ATP production.

CoQ10 has been shown to stimulate mitochondrial biogenesis. This can enhance mitochondrial function and energy metabolism. CoQ10 levels decline with age and in various diseases, and supplementation with CoQ10 has been shown to improve mitochondrial function and reduce oxidative stress in animal and human studies.

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MOTS-c

Mitochondrial Open Reading Frame of the 12S rRNA-c (MOTS-c) and is a 16-amino acid peptide that is encoded by a mitochondrial gene. This peptide can stimulate mitochondrial biogenesis and has also shown potent antioxidant properties. Interestingly, this peptide can improve insulin sensitivity by AMPK signaling in skeletal muscle.

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Creatine

Creatine is an extremely popular supplement, usually used in the fitness community and is a staple ingredient in almost any worthwhile pre-workout supplements. Creatine acts as ATP storage. During anaerobic exercise, the cell no longer has adequate oxygen supply, therefore the cell depends on alternative forms of making ATP. One such way is through creatine and creatine kinase. By increasing creatine in your skeletal muscle, you allow the muscle to have a little extra ATP during times of physical stress. Creatine has also been shown to prevent structural damage of mitochondria during stress.

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Vitamin B3, NR, NMN, NAD+

NAD is a coenzyme involved in redox reactions, making it vital to energy metabolism. It is directly involved in glycolysis and the citric acid cycle. It also seems that as we age, our NAD+ levels decline, making energy metabolism less efficient. The issue is that NAD+ is a polar molecule, unable to cross the cell membrane without the help of transporters. The equilibrative nucleoside transporter (ENT) family of proteins can shuttle NAD from the blood/lumen into the cell, however, increasing NAD above supraphysiological levels may not yield any beneficial returns in energy because of ENT bottleneck. To overcome this obstacle, we can supplement with primitive forms of NAD, molecules such as vitamin B3, NR, or NMN. These molecules can be transformed into NAD. The evidence behind supplementation of these molecules is shaky, therefore, experimenting with different dosages and combinations of these compounds may yield the best result for you.

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Methylene Blue

Methylene blue has also been studied for its potential therapeutic effects on a range of conditions, including neurodegenerative diseases and mood disorders. It has been shown to have antioxidant and anti-inflammatory properties, and to improve mitochondrial function and energy metabolism.

One of the key mechanisms of methylene blue is its ability to act as an electron carrier in the mitochondrial respiratory chain, which handles the production of ATP. Methylene blue can accept electrons from the respiratory chain and donate them to oxygen, helping to maintain mitochondrial function and energy metabolism.

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Conclusion

Using exogenous compounds such as methylene blue, creatine, CoQ10, and carnitine can support mitochondrial function. By supporting mitochondrial function, energy levels in the cell can be properly regulated, thus enhancing well-being and performance. This list of supplements may serve useful for folks whom are above 40 years of age, or anyone looking to optimize their energy.

Disclaimer

This is not medical advice, as I am not a board certified medical doctor. I do not directly recommend taking any compound without the reader doing their own research, assessing the risks, and when warranted, speaking to their physician.

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Introduction

I have spoken to hundreds of clients, from various walks of life, with different backgrounds and future goals, yet the confusion around losing weight remains the same. Many people think, eat less, lose weight, and yes, in principle, that is correct, but two months down the line, they haven’t lost a pound. The concept of losing weight is easy, but altering your diet is hard. What foods are good? What foods are bad for you? How much should I eat? When should I eat? These questions lie beneath the surface of the iceberg that is losing weight.

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Searching for the “Right” Foods

Many of these questions are inherently hard to answer. An example is food sensitivity. Your cousin may not tolerate a cup of pasta at dinner, but you may have no issues with digesting pasta. There are several factors that make a food “good” or “bad”, some of these are listed below:.

• How do you feel after eating it?
• Is this food nutrient-rich?
• How is this food on a caloric to satiety scale?

Let’s go through an example. An 8oz serving of chicken. Personally, I enjoy eating chicken. It is delicious, plus I do not feel bloated or have any digestion issues after eating it. This food contains lots of protein, B6, B12, and zinc, which are vital nutrients. In terms of calories, 8oz of lean chicken breast is around 350 kcalories and along with some veggies, this fills me up and curves my hunger. According to these results, chicken should be a staple in my diet.

Whenever you are at the store, shopping for your weekly groceries, be sure to ask yourself these questions about the food you are purchasing.

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Change your Palate

On average, the average person eats 7-13 different meals. Think about it. You usually just eat the same 10 meals repeatedly. Why am I telling you this? If you can switch just 5 of those meals to a “healthier” option, you will see significant benefits in your day-to-day life. Instead of just pizza for dinner, eat a small serving of pasta, with a meat, and a side of vegetables or whatever foods you found that work for you (using the section above). As time goes by, you will see the remaining meals slowly turn into healthier options as a positive feedback loop has been initiated. As you eat better, you feel better, thus reinforcing your good eating behaviors.

Journaling

Keeping a food journal can help in two major. First, it will help you make smarter decisions about the food you eat. If you didn’t feel so great after that meal, write it down, so in the future you avoid the food that caused you discomfort. Second, tracking the amount of calories you eat on a daily/weekly basis can help you along the weight loss journey if that is your goal. Keeping your caloric intake steady throughout the week can help stabilize your weight and hunger. This food journal can be broken down into many parts. One example is shown below:

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Concluding Remarks

To summarize, we are all different. We all prefer and react differently to certain foods, therefore, there is no “one diet for all”. Even though personalizing your diet is a daunting task, breaking it down into bite-sized pieces allows for a quick and easy transition with minimal stress. The first step is to ask yourself questions about the food you are eating. They can be as simple as “is this food making me feel good?” The next step is to use those answers to incorporate new meals into your life. Replace the old nutrient-scarce meals with new nutrient-dense and satiating meals. The last step is to track all of this. Keeping a record of what foods you respond well to is important for future planning and to maintain your healthy lifestyle.

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What is the Gut Microbiome?

The gut microbiome is the complex community of microorganisms, including bacteria, viruses, and fungi that live in the digestive tract of humans and other animals. The gut microbiome plays a vital role in digestion and nutrient absorption and also has important interactions with the immune system,the central nervous system, and our endocrine system. The gut microbiome is influenced by a variety of factors, including diet, environment, genetics, and medication use. Research has shown that an imbalance in the gut microbiome, known as dysbiosis, may be associated with a range of health conditions, including inflammatory bowel disease, obesity, and mental health disorders such as anxiety and depression.

Scientists have often referenced this so-called “dysbiosis” or “imbalance in the gut microbiome” but what exactly does that mean? They are talking about an imbalance in the abundance of good and bad bacteria. Herein, good bacteria, also known as beneficial or commensal bacteria, are types of microorganisms that have a positive impact on human health. They play a vital role in digestion, nutrient absorption, and immune system function, and help to prevent the growth of harmful bacteria. Examples of good bacteria commonly found in the gut microbiome include Bifidobacterium, Lactobacillus, and Faecalibacterium prausnitzii.

This good bacteria is in contrast to bad bacteria, also known as harmful or pathogenic bacteria. These are types of microorganisms that can have a negative impact on human health. They can cause infection, inflammation, and damage to the gut lining, and may disrupt the balance of the gut microbiome. Examples of bad bacteria that can be found in the gut microbiome include Clostridium difficile, Salmonella, and Escherichia coli (E. coli).

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The Gut Microbiome and The Brain

The gut microbiome can influence the brain through a complex network of communication pathways known as the gut-brain axis. A connection between the gut and the brain is formed through the vagus nerve, providing two-way communication. The gut microbiome produces a variety of molecules, such as neurotransmitters, hormones, and metabolites, that can directly or indirectly affect brain function.

Research has shown that the gut microbiome can influence a range of brain functions, including mood, cognition, and behavior. For example, studies have found that changes in the gut microbiome can affect levels of neurotransmitters such as serotonin and dopamine, which are important for regulating mood and motivation. Some studies have found links between the gut microbiome and conditions such as anxiety, depression, and autism spectrum disorders.

The gut microbiome can also influence the immune system, which can affect brain function. Dysbiosis, or an imbalance in the gut microbiome, has been linked to chronic inflammation and immune dysregulation, which can contribute to a range of neurological and psychiatric disorders.

Overall, the relationship between the gut microbiome and the brain is complex and multifaceted, and there is still much to learn about the specific mechanisms by which the gut microbiome influences brain function.

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How Can We Promote a Healthy Microbiome?

While this list is non-exhaustive, it contains practical ways to promote a healthier gut microbiome. First on the list should be no surprise. Avoid Antibiotics. These compounds kill bacteria and, while they are extremely beneficial when used in the correct context, they are over-prescribed and kill healthy and bad bacteria alike. Balanced Diet. A well-balanced diet is going to promote a healthy gut microbiome, but what seems to be missing is the fact that diet is extremely personal. There is not a one-diet cures-all. You should experiment with foods rigorously and explore how they make you feel. Exercise. Another keystone to promoting a healthy gut microbiome is by regularly exercising. This can come in many shapes, from resistance training to cardiovascular endurance. The choice is yours. Just stick to it. The last on my list is to avoid alcohol at all costs. This goes hand in hand with managing your diet, but it also seems to be the exception to a lot of my clients. It is not. There are several studies that discuss the negative affects of alcohol.

Here are some other practical ways you can promote a healthy gut microbiome.

• Manage your stress levels
• Get enough quality sleep
• Talk to your physician about pre- and probiotics

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Concluding Remarks

The gut microbiome refers to the micro-organisms and their activity, for example, their structural elements, genomes and metabolites. A dysregulated microbiome can lead to gut inflammation, the release of chemicals that interfere with brain chemistry, and immune issues. Meanwhile, a healthy gut microbiome facilitates adequate nutrient absorption, maintains intestinal linings, and acts to regulate gut hormones. Going from an unhealthy gut to a healthy gut is no easy task but can be accomplished by creating new habits such as eating a personalized diet, exercising, avoiding antibiotics and alcohol, and getting good sleep.

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Reference

1. https://www.nature.com/articles/s41398-023-02325-5
2. https://www.nature.com/articles/s41591-023-02260-4
3. https://www.nature.com/articles/s41598-023-31730-5

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Introduction

Many of us have heard that exercise has profound effects on our well-being. What many of us have not heard is that light exercise may have a direct, beneficial impact on our quality of life. The average American walks nearly 4 to 5 thousand steps or 1.5-2 miles per day according to the Mayo clinic. Considering that only 24% of Americans meet the physical activity guidelines, this average step count is far too low.

Like America, Saudi Arabia’s step count prior to 2020 was a measly 3800 steps per day, awarding them as a top contender in the world’s least physically active nation. To combat this, the kingdom started the “Walking Challenge”, an ingenious nationalistic activity that promoted each person to take 280,000 steps per month, or 9,205 steps per day. This step goal nearly tripled the reported step average.

A recent paper, published in Scientific Reports (2023), found that this increase in daily step count had a positive association with quality of life. This paper highlights the notion that a community project aimed at improving the livelihood of its citizens may benefit several nations across the world, such as America, where obesity rates heave steadily increased in the last decade.

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The Evidence

The current study had 200 employees from a University in Saudi Arabia, with a majority of the participants being female (n=124) in which a questionnaire was filled out before (“Before Challenge”) and after the walking challenge period (“After Challenge”). The duration of the challenge period was 30 days, starting on the first of March and ending on the 31 of March. During this period, participants were asked to walk 280,000 steps, or 9,032 steps per day. After the challenge, participants were asked to fill out an “After Challenge” questionnaire and the health-related quality of life measurement (HQoL) was calculated. It was concluded that walking nearly 10,000 steps per day can significantly increase the subject’s quality of life.

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The Impact

While this article has many shortcomings, including a small sample size and biased distribution of biological sex, it reinforces a positive behavior. The positive association between walking and quality of life further supports the notion that exercise has profound effects outside of physical health. Going to the gym is a hassle, especially for people who may have had a bad gym experience or feel intimidated in that environment. By starting your exercise journey with long-distance walks, your quality of life improves, your mood improves, and over-time, that anxiety about being “too out of shape” for the gym may dwindle away. Exercise is a well-known activity to decrease many health risks, including cardiovascular disease and diabetes. However, as obesity rates continue to climb, it seems as if the public feels disconnected from the importance of exercise. These disconnects can be attributed to a myriad of things, including poor time prioritization, poor availability of nutritious foods, and stress. The good news is that walking is a free, non-time intensive exercise program that can elevate your mood and possibly help motivate you to get into other types of physical activity, such as resistance training.

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Highlights

• As a national vision, Saudi Arabia started the walking challenge, aiming to increase physical well-being by increasing daily step count.
• Participants in the challenge had reported significant improvements in their quality of life when compared to reports taken before the challenge.
• Walking more every day can be beneficial to your life and set you up for success.

Supplement Review #8: Noopept

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What is Noopept?

Noopept is a synthetic compound, structurally similar to pireracetam, a popular nootropic, that was synthesized in Russia in the 1990s. Noopept was found to be a multifaceted cognitive enhancing agent, making it an extremely promising therapeutic for neurodegenerative diseases and cognitive decline. Noopept has a short half-life, with studies reporting no accumulation in the brain 1 hour post-administration, making it a great candidate for daily use. While noopept’s exact mechanism of action is not fully understood, research has concluded that it can (1) increase acetylcholine production in the brain (2) regulate NMDA and AMPA receptors and (3) act as a neuroprotective agent. Through these pathways noopept has been reported to slow the progression of Alzheimer’s disease and other diseases in multiple animal models. Although this compound is used in Russia, there is currently limited human-related research published on its safety and efficacy.

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The Benefits of Noopept

Noopept is a secondary nootropic, a self-defined class of nootropics that acutely improves cognitive performance and provides long-term benefits. This is opposed to a primary nootropic, which only acutely improves cognitive performance. As a secondary nootropic, noopept acts to improve cognitive performance acutely and chronically through many pathways. The first pathway (ranking is subjective) is through increasing nerve growth factor (NGF) and brain-derived neurotropic factor (BDNF) expression in the hippocampus. Ostrovskaya and colleagues found that long-term dosing of noopept, NGF and BDNF expression was higher in the rat hippocampus, the brain structure most associated with the formation, consolidation, and retrieval of memories. By increasing these growth signals in the hippocampus, more neurons may spawn, thus improving recall and increasing your performance. Similar research has also found that noopept administration led to an increase in hippocampal CA1 pyramidal cells, which are the major players in memory consolidation.

Noopept also works to elevate acetylcholine signaling, one of the most prominent chemicals for improving cognitive performance. Furthermore, noopept has been found to increase the density of nicotinic acetylcholine receptors (nAChRs) in the hippocampus. These receptors are important for modulating the activity of ACh in the brain, and play a key role in learning and memory processes.

It has also been shown that noopept can decrease the inflammation of neurons exposed to a pro-inflammatory agent and increase their chance of survival. In an animal model, noopept dramatically reduced inflammatory marker, interleukin-6 (IL-6) to rats given a proinflammatory drug. Taken together, noopept can work to improve acute cognitive processes through increasing acetylcholine signaling and the density of nAChRs in the hippocampus. Noopept also works to improve cognition in the long-term by increasing BDNF, NGF, and reducing inflammation in the brain.

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What to Expect?

As a strictly anecdotal section coming from client and personal experiences, this information may not relate to you as individual variance comes into the equation. It is recommended to take noopept at doses ranging from 10 to 30 milligrams/day orally and 1 to 10 milligrams/day nasally. At these doses, users may report slight stimulation and increased clarity, most likely because of acetylcholine signaling. Many long-term users notice the benefits after 2 weeks of daily dosing. These benefits include a decrease in post-exercise brain fog, a decrease in mental fatigue, and a more motivated feeling towards naturally unrewarding work. These reports should be taken with a grain of salt, and while I may conduct rigorous self-experimentation, these anecdotal reports are completely subjective and subject to bias.

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Can I Combine Noopept with other Nootropics?

The short answer is yes! Of course, there is a more correct way to create “stacks”, or combinations of compounds that yield increased productivity greater than the sum of each individual compound. Noopept can increase acetylcholine signaling, but if you do not have enough acetylcholine available, the positive effect of noopept is blunted. Therefore, noopept is usually supplemented in tandem with CDP-choline or Alpha-GPC.

Along with this, noopept can increase neurogenesis, which requires phosphatidylcholine (PC) and fats to maintain membrane integrity. A powerful neuroprotective/neurogenesis stack is noopept + UMP + DHA + CDP-choline. This stack touches on increasing BDNF with noopept, PC with UMP and choline, and fatty acids with DHA.

There are many ways to create nootropic stacks. The stacks should be tweaked to what you desire as the user. Do you want to be stimulated? Calm? Mentally clear? These factors must be considered when combining nootropics. If you would like to learn more about creating nootropic stacks, reach out to me and get started on improving your productivity.

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