Top 47 Surprising and Science-Backed Ways To Lose Weight

You Need Only One Weak Link For The Chain To Break

These are the best/most legit ways to lose weight that I’ve come across.

If you feel you’re keeping “most” of these things, it’s not enough.  If you’re genetically predisposed to gain weight, any weak link will get you.  Keep a tight ship.  If you’re obese, it means you aren’t keeping to one of these things enough.

For example, if you’re chronically stressed, sleeping 5 hours a night or you don’t have a tight circadian rhythm, I don’t care if you’re following everything else exactly.

There only needs to be one weak link for the chain to break.  And if you’re obese, then you’ve got a missing link.

I see people trying to eat more whole grains, but then they’re exposed to long light cycles with artificial blue light at night.  They stay up late, sleep little and have a chronically activated stress response.  Then they wonder why they’re obese.

You probably think you’ve “tried everything” to lose weight.  If you’re not keeping to this, you haven’t tried anything valuable. And I keep everything here pretty much – or at least I’m actively working on it.

When you keep EVERYTHING here, then you can start complaining in the comments section that you’ve tried it all and you still can’t lose weight.

The Basics

This post is not at odds with the fact that if you reduce your calories below a certain point, you will lose weight.

Of course energy balance matters.  I am not aware of any fat holocaust survivors. The problem is, we aren’t mutants or imprisoned.  Just like we can’t be expected to work at a boring job for 16 hours a day, we can’t expect to combat hunger for 16 hours a day.  We have limited willpower.

Also, if our metabolism isn’t working right, we will have to reduce our calories to an unhealthy level in order to lose weight.  You will feel weak, tired, anxious and depressed if you just “eat less” if your body is broken.

We need to look at what factors influence hunger and metabolism.

There are a bunch of factors that cause us to be hungry and eat more, which makes up one side of the energy balance equation.

Then there’s a whole bunch of factors that cause the burning of fat and energy expenditure.  This is the other side of the equation.

Many obese or fat people care very much about losing weight, but their body isn’t functioning the way it’s supposed to.   So it’s not fair to blame someone who is obese.

I’d also like to add that once people become obese, it’s not as easy to lose the weight as if you had good eating habits all along.

This is why if you’re not losing weight without supplements, then it’s time to add them in because now you are reversing a disease.  And we know reversing something is harder than preventing it – an ounce of prevention is worth a pound of cure.   So maybe doing most of these things would’ve sufficed to prevent you from becoming overweight, but once you’re overweight, you better be doing everything to the last letter here.

However, supplements and drugs should be used only after you’ve tried everything else.

See if your genetics are the reason you are sick. 

1) Take Care of Your Circadian Rhythm

Research over the past few decades has recognized the importance of circadian biology in obesity.

Circadian biology has a massive influence on energy balance and metabolism.  (R)

Mice who eat 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. (R)  Obviously, their metabolism shifted.

A dysrupted circadian rhythm is why we see shift workers are at seriously increased risk of obesity. (R)

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 energy metabolism. (R)

Read this post to take care of your circadian rhythm.

2) Eat Within a 12 Hour Window

The window starts when you get up…so don’t eat 12 hours after you get up…Do not eat after, even a little…See my blurb on it…

This is really part of the circadian rhythm, but I thought I’d emphasize this more.

There are limited circumstances where you can consume a little raw honey before bed – if you get hypoglycemic all the time.  But if your circadian rhythm is good, you won’t get hypoglycemic.

Caloric intake after 8:00 PM increases the risk of obesity, independent of sleep timing and duration (R).

In addition, eating in the evening or before sleep predisposes individuals to weight gain through higher total calories (R).

3) Get More Sun

Sun increases MSH, which helps you tan…MSH will decrease appetite. (R)

UV decreases obesity in animals and that is independent of vitamin D status (R).

Vitamin D deficiency is suspected to be a cause of obesity (R).

Sun also increases BDNF, which helps reduce appetite.

Sun later in the day increases Nitric Oxide, which has multiple mechanisms by which it causes weight loss.

Nitric Oxide (NO), as a signaling molecule, stimulates glucose uptake as well as glucose and fatty acid breakdown in muscle, heart, liver and fat tissue; inhibits the synthesis of glucose, glycogen, and fat in target tissues (e.g., liver and adipose); and enhances fat breakdown in fat cells (R).

NO stimulates AMPK, resulting in a decreased expression of genes related to fat and glucose creation (R).

NO increases the activation (phosphorylation) of hormone-sensitive lipase and perilipins, which results in the breakdown of fat (R).

NO activates expression of PGC-1a, thereby enhancing mitochondrial creation and function (R).

NO increases blood flow to insulin-sensitive tissues, promoting uptake of glucose and fat, which removes it from circulation (R).

Outdoor lighting will allow you to reset your circadian rhythm.

Sun will decrease inflammation (increase it in the short run), oxidative stress (increase it in the short run) and psychological stress.   So getting a good amount of sun is critical to losing weight.

If you’re scared of skin cancer, keeping to a circadian rhythm will help with that, as skin protection of UV has a circadian rhythm. (R)

What about cancer?  If you avoid sun, you can decrease your risk of melanoma, but you  increase your risk of non-Hodgkin’s lymphoma, colon, squamous cell lung, pleural, prostate, kidney, and bladder cancers. So, overall, your cancer risk goes up (R).

If I know I’m getting more than 30 minutes of sun, I make sure to take 12mg Astaxanthin.  I never wear sunscreen.

4) Get Sun or Bright Light Upon Awakening

Besides the amount of sun, the timing of sun is also important.

Intense light exposure, particularly in the morning, is associated with a lower BMI independent of sleep duration and timing (R).

Specifically, having a majority of the average daily light exposure above 500 lux earlier in the day was associated with a lower BMI (R).

In practical terms, for every hour later of light over 500 lux in the day, there was a 1.28 unit increase in BMI (R).

In particular, red and green light exposure in the morning for two hours immediately upon waking in sleep restricted (5 hours/night) individuals altered the levels of the satiety hormones, leptin and ghrelin.  Specifically, red and green light increased leptin and decreased ghrelin (R), both of which cause reduced hunger following sleep deprivation.

Exposure to at least 45 minutes of morning light (between 6–9 am at 1300 lux) for 3 weeks in obese women resulted in reduced body fat and appetite (R).

5) Block Out Blue Light At Night

Increased light exposure has been associated with obesity in both humans and mice (R).

Blue light at night can cause weight gain. (R, R2)

Even dim light at night disrupts the circadian clock and increases body weight (R).

Studies have shown that that 35% of the variance in BMI is caused by light exposure – in particular at night (R).

Prolonging daily light exposure increases obesity by decreasing energy expenditure rather than increasing food intake or activity (R).

This was caused by a light-exposure period-dependent reduction of the noradrenergic activation of brown adipose tissue that has recently been shown to contribute substantially to energy expenditure by converting fatty acids and glucose into heat (R).

It’s critical to wear red glasses for four hours before bed.  Make sure to use black tape to cover any electronics that emit blue or green light and put your shades down at night if light is coming in.

6) Get More and Better Quality Sleep (at least 8 hours)

Short sleep duration is independently associated with weight gain in many studies (R, R2).

Short sleep duration raises the risk of obesity by 89% in children and 55% in adults (R).

Poor sleep can increase hunger and cravings and disrupt hunger hormones like ghrelin and leptin (R, R2).

If your quality or quantity of sleep is bad, everything else will be out of whack.

If you’re waking up in the middle of the night, that’s bad news.

Fix your sleep.

7) Expose Yourself to Colder Temperatures

This means take cold showers, wear an Ice Helmet/Cryohelmet, use fewer layers, etc…You should make sure you’re shivering daily, multiple times in the day.  If you don’t see goosebumps at least a few times in the day, you’re not cold often enough.

Cold increases TRH (an appetite suppressant) (R), T3, T3 uptake and the production and burning of brown fat.

If you’re stumped in your weight loss efforts, take ice baths.

8) Reduce Stress

Stress is known to cause weight gain.

Stress increases cortisol and dynorphin, both of which cause weight gain… (R, R2)

Stress increases glutamate, which increases appetite. (R)

Stress decreases NGF and BDNF, both of which are appetite suppressors.

Stress will make our brains more serotonin resistant (R) and serotonin suppresses appetite in our brains…(R)

Stress also causes resistance to dopamine, which may cause us to eat more, as we’ll need to eat more food for the same rewarding effects. (R)

Palatable foods really do ease the edge when we’re feeling stressed.

I had a client who said she barely ate, but she was overweight and had diabetes.   Upon further investigation, she said she ate a tub of ice cream on a nightly basis and she needed it because there was a lot of problems in her life.

If you’ve got a lot of mental baggage and you find yourself eating to comfort yourself, you need to do some serious self-reflection, meditation and simplify your life.

9) Diet: Eat These Foods

Eat more protein (best in the form of seafood) – instead of other foods…

Studies on high protein diets show that they increase fat burning, reduce appetite and lead to automatic weight loss (R, R2, R3)

Consume more fish, seafood, vegetables, fruits and seeds like chia and flax, which have lots of soluble and insoluble fiber- instead of other foods, not in addition to….

Fish causes leptin to decrease (R) and higher leptin is associated with obesity (even though leptin is a satiating hormone).

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.  (R)

Vegetables are rich in soluble fiber, which has been shown to cause weight loss in some studies (R, R2, R3)….Fiber gets broken down by bacteria in the digestive tract to produce butyrate, which has weight loss effects in animals. (R)

If you’re consuming animal foods, you’ll get adequate levels of fat, which increases CCK – a hormone that decreases appetite…

Legumes are also beneficial (they release CCK), but if you’re predisposed to inflammatory or autoimmune conditions, you might want to cut them out, because inflammation will disturb your circadian rhythm.

Low glycemic foods are important to prevent hypoglycemia and insulin resistance.  Cut out sugar, flours, etc….Gluten also stimulates appetite in many.

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 (R).

Soups are great.  Some studies have shown 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 (R, R2).

Boiled potatoes scored the highest in satiation of all the foods tested. (R)

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 (R).

Be wary of lectins.  For a portion of the population, lectins may cause leptin resistance (R), which interferes with the ability of leptin to create a satiating effect.

Reduce carbs.  Different people will do differently with carbs.  Most people will lose more weight by reducing carbs. On the one hand, carbs increase serotonin, which decreases appetite. (R)  Hence, people feel more relaxed and satiated after carbs.  On the other, it increases insulin, which causes weight gain, (but also satiation in the short term).

Cut out or reduce bad oils…get your fats from fish, Caprylic acid  oil, liver,  meats/chicken, Black Cumin Seed Oil and/or extra virgin olive oil (1-2 tbsp)…Oils are energy dense and you get adequate amounts of fat without oils.  If you aren’t eating nuts or seeds, you can include some EVOO.

An olive oil-enriched diet brought about greater weight loss than a lower-fat diet in an 8-week comparison. (R) Use olive oil INSTEAD OF, not in addition to other calories.  Replace saturated fat-filled oils with olive oil(olive oil already has saturated fat).

Oleic acid, the main fatty acid found in olive oil, excites neurons that cause weight loss (POMC) (R).

Linoleic acid, found in vegetable oils, and table sugar synergistically increased the expression of genes involved in fat creation (R).  Palatinose (sugar substitute) and oleic acid did not have these effects (R).

Consumption of MCT oil as part of a weight-loss plan improves weight loss compared with olive oil, in a 8-week study. (R)

This is why I recommend Caprylic acid oil.

Many people assume coconut oil is mostly MCTs, but it’s not.  Coconut oil is mostly Lauric acid, which causes me and animals serious inflammation and insulin resistance, and it’s not an MCT.  The real MCTs have a better effect for me, and that’s what I’d recommend for weight loss (INSTEAD of other calories, not in addition to).

I’d recommend you choose your oils wisely, as fat is energy dense.  That’s why I recommend whole foods, olive oil, and Caprylic acid oil.

Studies consistently show that dieters who eat less energy dense foods lose more weight than those who eat foods with a high energy density (R, R2, R3).

In one study, women who ate soup (low energy density) lost 50% more weight than women who ate an energy dense snack (R).

10) Eat Less, But Not So Little That You Binge

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, you’re going too low on your calories.

If you’re hungry then include more of the RIGHT calories.

11) Exercise

Do high-intensity exercise, which is probably the best.  Adrenaline  enhances the release of fatty acids from fat tissue (R) and Norepinephrine suppresses food intake (R).  Think of the thin/anxious person…

Exercise also increases endorphins, which activate mu-opioid receptors, which suppresses appetite. (R)   See a whole list of ways to naturally activate opioids.

Any exercise is good, though. Aerobic exercise (like walking, running, swimming, etc) has been shown to cause major reductions in belly fat in some studies. (R, R2)

The bottom line is you need to move.

Stand, get a Treadmill Desk, bike to work, do yoga…mix it up….This is will burn calorie and increase BDNF, which causes us to eat less.(R)

12) Do Yoga

How many fat yogis do you see?   Yoga increases NGF (R, R2), which causes us to eat less. (R)

Semen also contains NGF, which means if you’re an orgasming man, you should injaculate.

13) Eat Right – Developing Health Habits

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 has an effect on how much we eat. (R)

Eat when you’re hungry, but don’t over-eat.

Be careful of eating mindlessly, for social reasons or for pleasure.  I find social occasions is when I and other people eat the most, and we’re eating not because we’re hungry.

You don’t want to be consuming too little because you’ll binge. It needs to be a lifestyle.  You need to find the right caloric level that satisfies your hunger, but not more.

14) Love and Be Playful

Oxytocin is released by positive human interactions and it decreases hunger (R).

Love also increases NGF (R), which reduces appetite.(R)  It also increases endorphins, which activate mu-opioid receptors.

15) Be Passionate

Be passionate about your work and life…When you’re bored, you will over-eat.  When you’re consumed or really busy, food is the last thing on your mind and you forget to eat.

16) Be Mindful and Meditate

If you are mindful of your food, you will eat less of it and enjoy it more.

Meditation will allow you to be less impulsive.

17) Drink Water

Drink a lot of water –Molecular Hydrogen water is better (R)…Hydrogen water increases FGF21, which results in burning of brown fat (R).

See: Water Drinking Induces Thermogenesis through Osmosensitive Mechanisms.

Researchers have estimated that 2 liters (68 oz) of water per day can make you burn an additional 96 calories (R).

The graph below shows how drinking 500 ml (17 oz) of water can boost metabolism by 24-30% over a period of 1 to 1.5 hours.

18) Chew/ Eat More Slowly

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 (R).

People who were instructed to eat more slowly ended up eating 67 fewer calories during a meal. They also enjoyed their meal more.

19) Prevent Hypoglycemia

Prevent hypoglycemia or low blood glucose  mainly through a healthy diet, with lots of veggies and fruits (fiber), a good amount of protein, and a decent amount of fat (but not too much)…

Hypoglycemia increases glutamate release, which increases appetite. (R)  Hence, I have clients who claim to have a voracious appetite, and I already know that they’ve got excess glutamate….hypoglycemia and stress are the most important causes of excess glutamate…

20) Lower Carb Intake

Insulin is one of the big four fattening hormones.  High glycemic index carbs will cause insulin spikes and insulin resistance.

Lower carb intake in general if you’re having a problem with weight loss.  My suggestion is to either go ketogenic or aim for 150g of carbs, spaced out throughout the day…

Also consume your carbs around the time you are exercising and towards the evening, when you’re more insulin sensitive (but not after your 12-hour window)…

If you have high insulin, lowering carbs is certainly more important.

21) Intermittent Fasting

Fast intermittently if you’re still having problems losing weight.

Results of one of the best studies we have 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. (R)

22) Take Care of Your Vagus Nerve

Increase your vagus nerve activity and oxygen through breathing exercises. Obese people have decreased heart rate variability and therefore vagal tone. (R)

23) Stay Away From Junk Food

Stay away from MSG (R), artificial sweeteners and junk food.

MSG has the capacity to increase appetite (R).

24) Breath In More Oxygen By Being Outside More

A paper published in Nature provides some evidence that elevated CO2 is one cause of obesity (R).

Coinciding with the increase in obesity, atmospheric CO2 concentration has increased more than 40% (R).

Furthermore, in modern societies, we spend more time indoors, where CO2often reaches even higher concentrations (R).

Increased CO2 concentration in inhaled air decreases the pH of blood, which in turn spills over to cerebrospinal fluids. 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 (R).

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 (R).

25) Optimize Your Hormones

Make sure your levels of Free and total T3, your growth hormone, and your testosterone (R) and estrogen are ideal.

Testosterone has massive effects for weight loss in men (R), and most men are deficient.  Put  LLLT on your testes for a few minutes every other day.

If you’re women with low estrogen (usually post-menopausal), estrogen replacement can help. (R)

Growth hormone or GHRH (its precursor) increases muscle and decreases fat.  Ipamorelin is the best for this.  It will help your sleep, too.  Low-dose growth hormone treatment with diet restriction accelerates body fat loss and increases muscle. (R)

Oxytocin (R), MSH (R) and TRH (R) will reduce your hunger levels. Having positive relationships, sun and cold will optimize these 3 hormones.

Put LLLT on your thyroid for a few minutes every other day if your thyroid hormones are low.

Keeping to a circadian rhythm is important for balancing all of your hormones.

Synthetic birth control hormones can cause you to gain weight (up to 2kg), so be careful of those.  They will increase fat and decrease muscle. (R)

26) Get a Sauna

Saunas can increase weight loss, mainly in overweight people. (R)

Saunas have been important for pretty much EVERY culture in the past few thousand years.

27) Include These Functional Foods That Cause Weight Loss

• Apple Cider Vinegar (Acetate results in appetite suppression (R)),
• Chili/Cayenne – capsaicin causes weight loss (R) – in part by increasing expenditure, reducing appetite and also causing vagus nerve blocking, which reduces excess weight (R,R2, R3, R4).Capsaicin‘s anti-obesity effect is in part by activating the transient receptor potential vanilloid-1 (TRPV1) channels (R)
• Dark Chocolate (R),
• Caprylic acid (instead of other oils not in addition to),
• Hi-maize/Resistant starch (to increase GLP-1)…Resistant starch has many mechanisms by which it can cause weight loss. (R)

28-43) Supplement Right

1. Probiotics (L gasseri, L. rhamnosus, B lactis) (R) – probiotics can help decrease intestinal inflammation, which can be a cause of weight gain (R),
2. Berberine  – obese people lost an average of 5 pounds in 12 weeks. (R)  Berberineinduces the development of brown fat and increases UCP1 and other thermogenic genes in white and brown fat…It works via AMPK and PGC-1α. Berberinealso inhibits AMPK activity in the hypothalamus.  
3. HMB – increases muscle mass and fat loss (R).
4. EGCG causes an average weight loss of 0.2 to 3.5kg with supplements… (R, R2)…EGCG inhibits MAO-B, which results in weight loss. (R) Green tea can 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% (R, R2, R3). For 2000 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 (R). Results may depend on the individual (R). Mechanism: EGCG increased CPT-1, UCP2, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) (R).
5. Glucomannan (R)- 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.
6. Forskolin decreases body fat in men (R) and mitigated body fat gains in women (R), in a small study.
7. CLA (small effect) – 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 (R). Another review study found an average of 3 pounds (1.3 kg) of weight loss compared to a placebo (R).
8. Calcium – Increasing dietary calcium significantly caused weight and fat loss and increased the percentage of fat lost from the trunk region (R).  In animals, calcium stimulated fat tissue uncoupling protein UCP2 and muscle UCP3and slightly increased core temperature.  Calcium increased fat busting/lipolysis decreased fatty acid synthesis, and reduced fat regain. (R)  If you don’t eat dairy or sardines daily, YOU WILL BE DEFICIENT in calcium. Take with K2 and D3 to prevent build up in your arteries.
9. Hops -Matured hop extract reduces body fat in healthy overweight humans: a randomized, double-blind, placebo-controlled parallel group study (R)
10. Green Coffee Extract/Chlorogenic acid/Kidney Bean Ext – a meta-analysis found that green coffee extract results in weight loss of about 2.5kg or 5.5 pounds. (R)  Kidney bean extract blocks carb absorption, which is a useful mechanism by which people can lose some weight. (R)
11. Mucuna to increase dopamine if you’ve got low levels.  It might, theoretically combat appetite…People with genetically fewer dopamine D2 receptors needed to consume more of a rewarding substance (such as drugs or food) to get that same effect. Manipulating dopamine levels altered eating behavior.. (R) For example, AA or AG of rs1800497, which is a DRD2 gene (I’m AG) is associated with less pleasure and a higher risk of obesity. (R)
12. 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. (R)
13. Synephrine/Bitter orange –Synephrine shares similar mechanisms with ephedrine, but is less potent. It can reduce appetite and significantly increase fat burning. (R)
14. 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. (R)
15. PRP – in a gene expression analysis, it was predict that PRP can help combat obesity (R).
16. Cissus Quadrangularis (R)

44-47) Relatively Safe Drugs to Think About

1. Nicotine -by far your best option.  Nicotine reduces appetite by activating nicotinic receptors in the lateral hypothalamus. (R) 
2. Caffeine (R, R2),
3. Metformin – metformin decreases food consumption and induces weight loss in obese people with type 2 diabetes. (R)
4. Ephedrine (be careful – not safe when overdone).

Supplements For Weight Loss With Positive Effects in Animals

Lipoic acid by decreasing hypothalamic AMPK (R)

L Gasseri (high-fat diet induced obesity) (R)

Reishi (experimentally obese) (R)

Blueberry peels (R)

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) (R)

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) (R)

I3C supplementation significantly ameliorated HFD-induced increases in body weight gain, visceral fat pad weights, and plasma lipid levels. The visceral adipose tissue mRNA levels of uncoupling proteins 1 and 3, crucial factors of thermogenesis, and their regulators such as sirtuin 1, peroxisome proliferator-activated receptor (PPAR) α and PPARγ coactivator 1α, which were down-regulated by HFD, were normalized by supplementation with I3C. decreased PPARγ2, and its target genes, such as leptin and adipocyte protein 2, in the visceral adipose tissue of mice maintained on the HFD. Furthermore, HFD-induced up-regulation in mRNA levels of inflammatory cytokines (tumor necrosis factor α, interferon β and interleukin 6) was significantly ameliorated by I3C.  (R)

L-Arginine and L-Citrulline via increasing nitric oxide (R)

Histidine via UCP-1 and increasing histamine neuron activation (R), and inhibiting cytokines and Nf-kB in fat cells (R).

Others, not recommended:

Amphetamines (R),

MAO Inhibitors (R).

An SNRI (a serotonin and norepinephrine reuptake inhibitor) called sibutramine results in weight loss, which is can be caused by increase serotonin and norepinephrine. (R)  This drug was withdrawn because of safety issues.