How to Lose Weight an Evidence-Based Approach


When people talk about weight loss, what they typically mean is losing body fat.  No one (okay almost no one) wants to lose lean body weight, which would mean losing muscle tissue, water in the muscle (helpful for strength) or bone.  So for the purposes of this article, when discussing weight loss we will be referring specifically to losing body fat.

It should be noted that anytime one loses body fat of any significant amount, lean mass will typically be lost as well (in most cases).  The goal of intelligent weight loss however is to minimize this loss of lean mass, and maximize the loss of fat mass.  The end result of this approach is to obtain a healthy physique with as much metabolically active tissue as possible.  This is so the individual can  eat as much food as possible while maintaining their new homeostasis.

Losing weight is the goal.  However, if you are losing metabolically active tissue then it will become harder and harder to keep losing weight as your calorie requirement becomes too low to be sustainable.


So comes the first big question.  What is needed to lose weight?  The answer is abundantly clear at this point that a calorie deficit is needed to lose weight.  The energy balance hypothesis has been even more concretely established in recent years despite a vocal contingent of people proposing a carbohydrate-insulin hypothesis.  Perhaps the most vocal among these in modern times has been Gary Taubes, who went super mainstream after appearing on the Joe Rogan Experience after multiple front page appearances on the New York Times Magazine where he claims that calories "don't really matter" and it's solely the consumption of carbohydrates that is driving the obesity epidemic.  I'm not going to delve into his research, as he was exposed pretty well by Stephan Guyenet on the show, and he has made his references available online. (1)

A ketogenic type diet theoretically should be beneficial for cancer patients, and some studies have been done on this but they are of low quality and so it is not known whether this intervention is useful or not in practice.  However, what is more valuable for us in the health and fitness space is the role that carbohydrate restriction can play in insulin sensitivity.  Insulin sensitivity is extremely important for anyone looking to maximize their body composition.  We want nutrients to be taken up and used by the muscles, not to circulate throughout the bloodstream and be converted into body fat.  Insulin is crucial in that role, and the more sensitive to our insulin we are, the more effectively nutrients are taken up by the muscles.

It is common for physique athletes to "carb cycle."  This is done in order to increase insulin sensitivity.  Again, the more sensitive to insulin we are, the more the food we eat will be used by the muscles, not stored in the liver or elsewhere as fat tissue.  What is not (typically) used in the fitness space is a low-carb or very-low-carb diet for an extended period of time.  This is because the benefits of switching to a LC or VLC diet do not continue to grow, and in fact it has been shown that these diets can increase LDL (bad cholesterol) over time with no additional benefit. (2)  I would recommend carb cycling periodically to keep insulin sensitivity high.  However I would not recommend a low carb diet for an extended period of time.


Ghrelin is a very important and multi-faceted hormone released by the stomach.  From there it crosses the blood-brain barrier and activates the hypothalamus. (3)

Dieting is difficult because the leaner we get, the hungrier we get.  This is probably a result (at least in part) of increased ghrelin levels in the body resulting from consuming less food. Ghrelin is secreted from the stomach as it empties, signalling the body to produce growth factor as well as making us feel hungry.  The most effective way to combat this effect in my opinion is to consume more food more often in order to decrease the stomach emptying signal to the brain. 

So we can minimize hunger by eating more food, and we simultaneously want to eat less calories.  This leads us to foods that have a large volume/calorie ratio.  This should minimize the ghrelin signaling that occurs during a cutting phase.

 Calories to Volume Graph



Leptin is the other main regulatory mechanism in the body that bears responsibility for body composition outcomes.  Leptin is produced by the adipose (fat) tissue and signals the body to feel satiated or full.  Patients who are born with a leptin deficiency have a high propensity for obesity. (4) Conversely, obese patients often have elevated leptin levels as a result of the large amount of fat tissue they have.  It is known that obese individuals are leptin resistant due to leptin treatment of obese individuals being unsuccessful.  Overall leptin is a very complicated hormone with a ton of interactions that are not well understood.  

"The pathologically increased circulating leptin is a biomarker of leptin resistance, which is common in obese individuals." (5)

The question is how can we increase our leptin sensitivity?  Resveratrol, caffeine, taurine, adequate vitamin A and D have been shown to ameliorate some aspects of leptin resistance. (6)  There are also drugs in development for this purpose, the most notable in recent years is semaglutide.  If you’re waiting for the magic pill, the pharmaceutical industry is hard at work trying to make it happen.  It is unlikely that a single drug will work in my opinion, due to the many hormones and complex interactions as well as the feedback mechanisms that take place after a period of weight loss (for example leptin decreases after losing weight, perhaps playing a role in weight regain or yo-yo dieting).

“Leptin is a potent insulin sensitiser”   “Leptin resistance occurs in response to a high-fat diet”  (7)


What is the role of protein in all of this?  Why the recommendations to eat so much protein?  There are several reasons why a high protein diet is recommended while dieting.  


Increased protein intake has been shown to be proportional to satiety.  This means the more protein we eat, the more full we will feel.  This has been well understood for 6 decades. 

“elevated concentration of blood or plasma amino acids, which cannot be channeled into protein synthesis, serves as a satiety signal for a food intake regulating mechanism and thereby results in depressed food intake” (8)

Muscle Mass

Fat-free mass (muscle mass and bone) is a driver of BMR or basal metabolic rate.  In other words, the amount of fat free mass you have is a factor in determining how many calories your body requires at rest.  The more calories your body requires at rest, the more food you can eat. 

BMR to FFM graph (12)

Fat-free mass can be preserved while dieting by increasing protein intake.  As a result, increasing the proportion of protein we consume as we reduce our caloric intake can maintain BMR (calories burned) by preserving fat free mass while simultaneously maximizing our satiety.

A too low absolute protein content of the diet contributes to the risk of BW regain. The success of the so-called 'low carb' diet that is usually high in protein can be attributed to the relatively high-protein content per se and not to the relatively lower carbohydrate content.” (9)

Resistance Training

The main purpose of resistance training as it relates to weight loss is to preserve fat free mass while dieting.  Regular resistance training has a plethora of health benefits, the most pertinent here being to increase the rate at which we lose body fat.  Weight training in conjunction with caloric restriction has been shown to be more effective than caloric restriction alone in a statistically significant way. (10)

In addition, weight training has been shown to be effective in improving fat metabolism. (11)

Meal Timing

A recent trend in the health and fitness sphere is intermittent or regular fasting, often combined with low carb dieting.  I have already delved a bit into low carb and why it is not optimal for weight loss, and I will briefly touch on intermittent fasting.

Late eaters who often skip breakfast were less effective in losing weight when compared with early eaters with all other measured factors being similar in one study. (13)  In my opinion, the insulin sensitizing effects of intermittent fasting could be better achieved via carb cycling, and are not worth the ghrelin induced binging that often occurs during the "feeding window." 

We also know from the literature that maximizing the number of muscle-protein synthesis events should lead to the maximal amount of fat free mass accumulation.

According to the International Society of Sports Nutrition, "Ingesting a 20-40 g protein dose (0.25-0.40 g/kg body mass/dose) of a high-quality source every three to 4 h appears to most favorably affect MPS rates when compared to other dietary patterns and is associated with improved body composition and performance outcomes"  (14)


After evaluating all of the available evidence, the best approach to losing weight for the vast majority of individuals is going to be the same.  

  1. Put yourself in a caloric deficit by either or both
    1. Reducing your caloric intake
    2. Increasing energy expenditure (cardiovascular exercise)
  2. Switch from moderate or high caloric density foods to lower caloric density foods.
  3. Increase your protein intake as an overall proportion of your calories.
  4. Resistance training
  5. Eat smaller meals more often (4 or 5) with a minimum of 0.7 to 1.0 gram of protein per pound of body weight in order to maximize MPS and minimize hunger.

Thanks for reading the article.  Feel free to comment below if you disagree or have pertinent information you'd like me to look at and I will consider the evidence and make changes or updates to the article as appropriate.  -James Strasshofer


(2) Goldenberg JZ, Day A, Brinkworth GD, et al. Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data. BMJ. 2021;372:m4743. Published 2021 Jan 13. doi:10.1136/bmj.m4743

(3) M.D.Klok, S. Jakobsdottir, M.L.Drent  “The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review”

(4) Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O'Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997 Jun 26;387(6636):903-8. doi: 10.1038/43185. PMID: 9202122.

(5) Liu J, Yang X, Yu S, Zheng R. The Leptin Resistance. Adv Exp Med Biol. 2018;1090:145-163. doi: 10.1007/978-981-13-1286-1_8. PMID: 30390289.

(6) Aragonès G, Ardid-Ruiz A, Ibars M, Suárez M, Bladé C. Modulation of leptin resistance by food compounds. Mol Nutr Food Res. 2016 Aug;60(8):1789-803. doi: 10.1002/mnfr.201500964. Epub 2016 Mar 1. PMID: 26842874.

(7) Koch CE, Lowe C, Pretz D, Steger J, Williams LM, Tups A. High-fat diet induces leptin resistance in leptin-deficient mice. J Neuroendocrinol. 2014 Feb;26(2):58-67. doi: 10.1111/jne.12131. PMID: 24382295.

(8) Westerterp-Plantenga, M., Lemmens, S., & Westerterp, K. (2012). Dietary protein – its role in satiety, energetics, weight loss and health. British Journal of Nutrition, 108(S2), S105-S112. doi:10.1017/S0007114512002589

(9) Westerterp-Plantenga MS, Lemmens SG, Westerterp KR. Dietary protein - its role in satiety, energetics, weight loss and health. Br J Nutr. 2012 Aug;108 Suppl 2:S105-12. doi: 10.1017/S0007114512002589. PMID: 23107521.

(10) Miller T, Mull S, Aragon AA, Krieger J, Schoenfeld BJ. Resistance Training Combined With Diet Decreases Body Fat While Preserving Lean Mass Independent of Resting Metabolic Rate: A Randomized Trial. Int J Sport Nutr Exerc Metab. 2018 Jan 1;28(1):46-54. doi: 10.1123/ijsnem.2017-0221. Epub 2018 Jan 24. PMID: 28871849.

(11) Yetgin MK, Agopyan A, Kucukler FK, Gedikbasi A, Yetgin S, Kayapinar FC, Ozbar N, Bicer B. The influence of physical training modalities on basal metabolic rate and leptin on obese adolescent boys. J Pak Med Assoc. 2018 Jun;68(6):929-931. PMID: 30325913.

(12) Alexandra M Johnstone, Sandra D Murison, Jackie S Duncan, Kellie A Rance, John R Speakman, Factors influencing variation in basal metabolic rate include fat-free mass, fat mass, age, and circulating thyroxine but not sex, circulating leptin, or triiodothyronine, The American Journal of Clinical Nutrition, Volume 82, Issue 5, November 2005, Pages 941–948,

(13) Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Apr;37(4):604-11. doi: 10.1038/ijo.2012.229. Epub 2013 Jan 29. Erratum in: Int J Obes (Lond). 2013 Apr;37(4):624. PMID: 23357955; PMCID: PMC3756673.

(14) Kerksick CM, Arent S, Schoenfeld BJ, et al. International society of sports nutrition position stand: nutrient timing. J Int Soc Sports Nutr. 2017;14:33. Published 2017 Aug 29. doi:10.1186/s12970-017-0189-4

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