The Science of Weight Loss
Looking for the “Weak Link” that Can Break the Chain
Healthy weight loss always involves an all-around approach.
It’s always a good idea to avoid unhealthy habits – such as smoking, fast food, overeating, being under a lot of stress, and drinking too much – that can bring your hormones and energy out of balance. Look to get regular exercise, enough nutrients, sleep, and follow a healthy circadian rhythm.
Keeping “most” of these things may not be enough, if one big factor if throwing off your balance. It could be chronic stress, sleep deprivation, or constantly doing overtime at your office job without getting any exercise.
But you probably won’t accomplish much if you start going to the gym regularly but keep on working long night shifts and eating fast food before going to bed at 6 am.
Keep a tight ship. There only needs to be one weak link for the chain to break.
When to See a Doctor
These “missing links” are manyfold, and it’s important to realize that you may not be able to consciously affect some of them.
Be it an eating disorder, hormonal imbalance, a mood disorder, or other, it’s important to talk to a qualified healthcare professional who will seek to uncover the underlying causes driving your weight struggles.
The next step is for your doctor to diagnose and treat the underlying condition contributing to your obesity. Afterward, you might need to see a nutritionist, psychotherapist, or run some labs – all depending on the identified cause behind your issues.
Remember, changes in biochemistry are not something that people can change on their own with the approaches listed below. Instead, the factors listed here are meant to reduce support healthy weight loss and general well-being.
Therefore, you may try the additional strategies listed below if you and your doctor determine that they could be appropriate. None of them should ever be done in place of what your doctor recommends or prescribes.
50 Factors that May Support Healthy Weight Loss
In this post, we will explore the science behind various factors that can influence hunger and metabolism.
Some factors may cause us to be hungry and eat more, which makes up one side of the energy balance equation.
Other factors may influence the burning of fat and energy expenditure. This is the other side of the equation.
Complex disorders like obesity always involve multiple possible factors – including biochemistry, environment, health status, and genetics – that may vary from one person to another.
Additionally, some human studies covered in this article deal with associations only, which means that a cause-and-effect relationship hasn’t been established.
A portion of the studies we bring up are highly experimental. For example, they may have been performed only in lab animals, and we can’t apply animal findings to humans.
1) Take Care of Your Circadian Rhythm
Research over the past few decades has recognized the importance of circadian biology in obesity. Scientists think that circadian biology may have a massive influence on energy balance and metabolism .
In lab settings, mice who ate at the wrong time (when it’s dark for humans) gained more weight, despite the absence of any significant differences in calorie intake or activity over the course of the experiment . The authors suspect that their metabolism shifted.
According to another theory, a disrupted circadian rhythm may be why shift workers seem to be at an increased risk of obesity .
Mice deficient in the core circadian CLOCK gene develop obesity. These mice have reduced levels and a flat rhythm of orexin, a neurotransmitter that increases wakefulness and energy metabolism .
Read this post to learn about natural factors that support a healthy circadian rhythm.
2) Get More and Better Quality Sleep
Directly died to circadian patterns, sleep is as important for metabolic health and energy use in the body. Short sleep duration has been independently associated with weight gain in several studies [3, 4].
In one study, short sleep duration raised the risk of obesity in both children and adults .
Scientists think that poor sleep may increase hunger and cravings and disrupt hunger hormones like ghrelin and leptin [6, 7].
Read about factors that can support restful sleep.
3) Reduce Stress
Stress is a known contributor to weight gain. Researchers explain that it increases cortisol and dynorphin, both of which can cause weight gain. It also increases glutamate, which is thought to increase appetite, and decreases NGF and BDNF, which are sometimes viewed as appetite suppressors [8, 9, 10].
According to one unverified theory, stress might also make our brains more “serotonin resistant” , and serotonin suppresses appetite . This hasn’t been proven, though.
Other researchers believe that stress increases dopamine resistance, which may cause people to eat more and require more food for the same rewarding effects .
4) Yoga & Meditation
Yoga increases NGF [14, 15], which might cause us to eat less. It’s also great for physical fitness and mental health. It can help you de-stress and become more mindful, especially combined with meditation and relaxation techniques. Directly tied to its effects on mindfulness, meditation can also help people become less impulsive and more moderate.
Regular exercise is great for overall health and it’s an indispensable part of any healthy weight loss regime.
There’s no one right way to exercise. This depends on your preferences and health status. Stand up and walk more often, get a treadmill desk, bike to work, do yoga… mix it up!
Being active burns calories and jump-starts metabolism. Some studies suggest it also increases BDNF, which supports mental health and might cause us to eat less .
If you’re not sure where to start, it would be a good idea to see a fitness coach to get you started.
One option is high-intensity exercise (HIIT). Some researchers hypothesize that HIIT increases adrenaline (which is supposed to enhance the release of fatty acids from fat tissue ) and Norepinephrine (which might suppress food intake) .
Exercise also increases endorphins, our “happiness chemicals,” which activate mu-opioid receptors and, in turn, suppress appetite . Find out about other factors that may naturally activate opioids.
Aerobic exercise (like walking, running, swimming, etc.) is also beneficial. It has been shown to reduce belly fat in some studies [20, 21].
6) Get More Sun
Scientists are investigating whether MSH, which is increased by sun exposure and helps people tan, can also decrease appetite .
Vitamin D deficiency is suspected to contribute to obesity in some cases, though more research is needed .
UV is hypothesized to decrease obesity in animals independent of vitamin D status .
Sun exposure is also thought to increase nitric oxide, which may help with weight loss and enhance blood flow by stimulating glucose uptake and fatty acid breakdown. It might also activate AMPK and PGC-1a to support mitochondrial health . These mechanisms haven’t been explored in humans.
Besides the amount of sun, some scientists think that the timing of sun exposure may also be important.
In one study, intense light exposure, particularly in the morning, was associated with a lower BMI independent of sleep duration and timing .
Specifically, having a majority of the average daily light exposure above 500 lux earlier in the day was associated with a lower BMI .
In particular, red and green light exposure in the morning for two hours immediately upon waking in sleep-restricted (5 hours/night) people altered the levels of the satiety hormones, leptin, and ghrelin. Red and green light increased leptin and decreased ghrelin , both of which have been linked with reduced hunger following sleep deprivation.
Exposure to at least 45 minutes of morning light (between 6-9 am at 1,300 lux) for 3 weeks in obese women resulted in reduced body fat and appetite. Although encouraging, more research is needed to verify the link between sunlight exposure and weight loss .
7) Block Out Blue Light At Night
Increased light exposure – especially at night – has been associated with obesity in both humans and mice. However, the research is still limited [28, 29].
Nonetheless, even dim light at night is hypothesized to disrupt the circadian clock and increases body weight .
Studies have suggested that 35% of the variance in BMI is caused by light exposure – in particular at night. Large studies need to verify this finding, though .
According to one theory, longer blue light exposure might increase obesity by decreasing energy expenditure rather than increasing food intake .
The authors claimed that light exposure reduced the noradrenergic activation of brown adipose tissue, which has recently been shown to contribute to energy use by converting fatty acids and glucose into heat .
Some people say they wear red glasses before bed to reduce blue light exposure. Others use black tape to cover electronics that emit blue or green light or blackout curtains to prevent street lights from coming in. These techniques have not been scientifically researched yet.
8) Love & Positive Social Interactions
Oxytocin is released when we engage in positive and loving human interactions. It makes us feel closeness and intimacy, and as an added benefit – it might also decrease hunger .
Some researchers think that love also increases NGF, which seems to reduce appetite. Being in love and engaging in positive social interactions also increases endorphins, which activate mu-opioid receptors to suppress hunger [31, 32].
9) Passion & Awe
Being passionate about your work and life may be protective against some forms of overeating, though the research is still scarce. Being in awe or entering any state of mind that is meaningful – and therefore, incompatible with boredom – may have a similar effect.
According to one theory, people who are bored are more likely to overeat or engage in other detrimental and addictive behaviors. In this sense, being bored marks a lack of meaning in the present situation and in life. Eating can be viewed as one distraction, especially when people seek “exciting” but unhealthy foods .
Little is known about the effect of saunas on weight loss, though they are popular. Saunas have been important for various cultures in the past few thousand years. Limited studies suggest that saunas can increase weight loss in overweight people. However, they’re not always safe – especially in people with heart problems – so be sure to check with your doctor first .
1) Get More Protein
Some research suggests that eating more protein instead of other macronutrients may support weight loss, metabolism, and satiety. High-protein diets appeared to increase fat burning and weight loss and reduce appetite in a couple of human studies [35, 36, 37].
2) Fish & Seafood
A couple of studies suggest that consuming more fish, seafood, vegetables, fruits and seeds like chia and flax (which have lots of soluble and insoluble fiber) instead of other foods may support weight loss.
Fish is hypothesized to reduce leptin ; higher leptin is associated with obesity. In young, overweight men, the inclusion of either lean or fatty fish, or fish oil as part of an energy-restricted diet resulted in approximately 1 kg more weight loss after 4 weeks, than did a similar diet without seafood or a supplement .
3) Veggies, Fruits & Fiber
Vegetables are rich in soluble fiber, which has been shown to cause weight loss in some studies [40, 41, 42]. Fiber gets broken down by bacteria in the digestive tract to produce butyrate, which has weight loss effects in animals .
Fruits are good, too. In a study of 91 obese individuals, eating half a fresh grapefruit before meals caused weight loss of 3.5 pounds (1.6 kg) over a period of 12 weeks .
Some human research suggests that eating the exact same food, except made in a soup instead of as solid food, makes people feel more satiated and eat significantly fewer calories [45, 46].
In several human studies, dieters who ate less energy dense foods lost more weight than those who ate foods with a high energy density [47, 48, 49].
In one study, women who ate soup (low energy density) lost 50% more weight than women who ate an energy-dense snack .
5) Other Satiating Foods
Boiled potatoes scored the highest in satiation of all the foods tested in one study .
Eggs over bagels: One study of 30 overweight women showed that eating eggs for breakfast, instead of bagels, increased satiety and made them eat less for the next 36 hours. Eggs are also much more nutritious than bagels .
6) Reduce Refined Carbs & Junk Food
According to the available evidence, most people will lose more weight by reducing carbs. On the one hand, carbs increase serotonin, which decreases appetite . Hence, people feel more relaxed and satiated after carbs. On the other, it increases insulin and weight gain in the long term.
Refined carbs like sugar, white bread, and pasta also lack nutrients and have several other detrimental health effects. These refined carbs are also high glycemic index and will cause insulin spikes and insulin resistance.
Junk food is one of the biggest drivers of the obesity epidemic worldwide. In addition, it may be a good idea to stay away from MSG  and artificial sweeteners, which are usually added junk food. MSG likely increases appetite .
7) Healthy Fats
Studies suggest that healthy fats support weight loss .
An olive oil-enriched diet brought about greater weight loss than a lower-fat diet in an 8-week comparison . Scientists are investigating whether oleic acid, the main fatty acid found in olive oil, excites neurons that cause weight loss (POMC) .
Consumption of MCT oil as part of a weight-loss plan improved weight loss compared with olive oil, in an 8-week study. Larger trials are needed .
Caprylic acid also helps build MCT oil in the body, but it hasn’t been independently researched for weight loss.
8) Other Functional Foods
These foods might also help, though the research is limited:
- Apple Cider Vinegar (hypothesized to increase appetite suppression )
- Chili/Cayenne – capsaicin may help with weight loss , possibly by increasing expenditure and reducing appetite [58, 59, 60, 61]. Capsaicin’s anti-obesity effect is in part by activating the transient receptor potential vanilloid-1 (TRPV1) channels 
- Dark Chocolate 
- Jo’s Resistant starch (to increase GLP-1) .
9) Eat Right – Developing Healthy Habits
Some nutritionists simply say that you should eat less overall, but not too little that you binge later on. If you’re bingeing or thinking about food all day or hoarding food, this might mean you’re going too low on your calories.
If you’re hungry, then include more of the right calories from some of the healthy foods mentioned above.
Aim to control your portion sizes and choose meal sizes that satisfy your hunger, but not more than your hunger demands.
Portion sizes and the containers we use can have an effect on how much we eat.
Be careful of eating mindlessly, for social reasons or for pleasure. People often say that social occasions are when they eat the most, and it’s not because they’re hungry.
Overall, looking to build a healthy and sustainable lifestyle. You need to find the right caloric level that satisfies your hunger and gives you the nutrients you need, but not more.
10) Drink Water
Drink a lot of water. It helps you stay hydrated and supports energy balance. Researchers have estimated that 2 liters (68 oz) of water per day can make you burn an additional 96 calories .
See: Water Drinking Induces Thermogenesis through Osmosensitive Mechanisms.
Limited studies suggest that Molecular Hydrogen water may be helpful. It’s hypothesized to increase FGF21, but human data are lacking. Plus, hydrogen water research is controversial and it’s hard to draw unbiased conclusions [66, 67].
11) Chew/ Eat More Slowly
According to one theory, if you chew your food well, you will eat less of it, enjoy it more and release more satiating hormones.
Eating slowly led to decreases in energy intake within meals in healthy women. People who were instructed to eat more slowly ended up eating 67 fewer calories during a meal. They also enjoyed their meal more .
12) Eating Within a 12 Hour Window
Eating within a 12-hour window usually involves having meals within the first 12 hours after waking up. For example, if you wake up at 8 am and have breakfast, your last meal of the day should be before 8 pm.
According to one study, caloric intake after 8:00 PM may increase the risk of obesity, independent of sleep timing and duration. Larger studies are needed to confirm this finding, though .
In addition, eating in the evening or before sleep may predispose people to weight gain as it tends to increase their higher total calorie count .
Other Aspects of Healthy Weight Loss
1) Maintaining Sugar Balance
A healthy diet may help prevent excessive sugar drops or spikes, especially if it includes lots of veggies and fruits (fiber), a good amount of protein, and a decent amount of healthy fats .
2) Vagus Nerve Activity
Experimental research suggests that increasing vagus nerve activity and oxygen through breathing exercises may support weight loss. This is based on a premise that obese people tend to have decreased heart rate variability and therefore vagal tone .
3) Proper Breathing & Being Outside More
A paper published in Nature provides some evidence that elevated CO2 is one cause of obesity .
Coinciding with the increase in obesity, atmospheric CO2 concentration has increased by more than 40% .
Furthermore, in modern societies, we spend more time indoors, where CO2 often reaches even higher concentrations .
The increased CO2 concentration in inhaled air decreases the pH of blood, which is hypothesized to reach the brain. Nerve cells in the hypothalamus that regulate appetite and wakefulness have been shown to be extremely sensitive to pH, doubling their activity if pH decreases by 0.1 units .
The study hypothesizes that an increased acidic load from atmospheric CO2 may potentially lead to increased appetite and energy intake, and decreased energy expenditure, and thereby contribute to the current obesity epidemic .
4) Hormonal Balance
The following hormones may also influence weight [74, 30, 22]:
- Free and total T3 (thyroid hormones)
- Growth hormone
Many other hormones and blood markers also play a role, especially glucose, cholesterol, and insulin. Therefore, this is not an extensive list of hormones involved in weight control.
Note: Birth control pills may increase weight gain in some women, so talk to your doctor if this is a concern for you .
Some of these supplements were only researched in animals, but human data are lacking to support their use for weight loss. Others are supported only by limited clinical trials and insufficient evidence.
- Berberine – researched in one study on obese people, who lost an average of 5 pounds in 12 weeks ; no other human studies are available. Berberine may increase UCP1 and other thermogenic genes in white and brown fat; thought to work via AMPK and PGC-1α; inhibits AMPK activity in the hypothalamus.
- HMB – hypothesized to increase muscle mass and fat loss .
- EGCG (a component of green tea) causes an average weight loss of 0.2 to 3.5kg in limited human studies [78, 79]. EGCG inhibits MAO-B, which may support weight loss [18, 80]; Green tea is hypothesized to make us burn more calories, even at rest. In most studies, this amounts to about a 3-4% increase, although some studies show an increase as high as 8% [81, 82, 83]. For 2,000 calories, 3-4% amounts to an additional 60-80 calories per day. In one study of 60 obese individuals, the group taking green tea extract lost 7.3 lbs (3.3 kg) and burned 183 more calories per day after 3 months . Results may depend on the individual .
- Glucomannan  – Glucomannan induced body weight reduction in healthy overweight subjects eating a healthy diet, whereas the addition of guar gum and alginate did not seem to cause additional loss of weight to a healthy diet.
- Forskolin decreased body fat in men  and mitigated body fat gains in women , in a small study.
- CLA (potentially insignificant)- In a review of 18 different studies, CLA caused weight loss of about 0.2 pounds (0.1 kg) per week, for up to 6 months . Another review study found an average of 3 pounds (1.3 kg) of weight loss compared to a placebo .
- Probiotics (L. gasseri, L. rhamnosus, B. lactis)  – hypothesized to decrease intestinal inflammation; may support gut health and weight control .
- Calcium – Increasing dietary calcium caused weight and fat loss and increased the percentage of fat lost from the trunk region ; in animals, potentially via UCP2 and muscle UCP3, fat busting/lipolysis, and reduced fat regain .
- Hops – Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study .
- Green Coffee Extract/Chlorogenic acid/Kidney Bean Ext – a meta-analysis found that green coffee extract may result in a weight loss of about 2.5kg or 5.5 pounds . Kidney bean extract might block carb absorption .
- Garcinia – A 2011 review that looked at 12 studies on garcinia cambogia found that, on average, it caused weight loss of about 2 pounds (0.88 kg) over several weeks .
- Synephrine/Bitter orange – Synephrine shares similar mechanisms with ephedrine, but is less potent. It is hypothesized to reduce appetite and increase fat burning .
- Meratrim – After 8 weeks, the Meratrim group had lost 11 pounds (5.2 kg) of weight and 4.7 inches (11.9 cm) off their waistlines .
- PRP – in a gene expression analysis, it was predicted that PRP may help combat obesity .
- Cissus Quadrangularis 
- Lipoic acid by decreasing hypothalamic AMPK 
- L Gasseri (high-fat diet induced obesity) 
- Reishi (experimentally obese) 
- Blueberry peels 
- Apple polyphenols (led to reduced Leptin, Perilipin, and sterol regulatory element binding transcription factor 1 (Srebf1) gene expression and increased aquaporin 7 (Aqp7), adipocyte enhancer binding protein 1 (Aebp1), and PGC-1a) .
- Carvacrol (by suppressing bone morphogenic protein, fibroblast growth factor 1- and galanin-mediated signaling, and it also attenuates the production of pro-inflammatory cytokines in visceral adipose tissues by inhibiting toll-like receptor 2 (TLR2)- and TLR4-mediated signaling) .
- I3C ameliorated increases in body weight gain from a high-fat diet in animals; hypothesized to normalize sirtuin 1, peroxisome proliferator-activated receptor (PPAR) α and PPARγ coactivator 1α, PPARγ2, and inflammatory cytokines .
- L-Arginine and L-Citrulline via increasing nitric oxide .
- Histidine via UCP-1 and increasing histamine neuron activation , and inhibiting cytokines and Nf-kB in fat cells .
Supplements have not been approved by the FDA for medical use. The FDA has not approved any supplement for obesity.
Have in mind that Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.
Additionally, supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
Results of one study of intermittent fasting in humans showed that fasting every other day for 12 weeks caused 32 people to lose an average of 12 pounds more than those who followed a daily program of calorie restriction. These people ate 25% of their calories every other day .
More research is needed and intermittent fasting is not suitable for everyone.
Caffeine may support weight loss, according to some research. On the other hand, coffee can also be inflammatory. Getting some caffeine from green tea, which also contains antioxidants, is likely a better idea [113, 114].