Protein-Sparing Modified Fast

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Abstract

A Protein-Sparing Modified Fast (PSMF) is a very-low-calorie, high-protein dietary intervention derived from clinical obesity treatment protocols¹, ², ³. It produces rapid fat loss while preserving lean mass by maintaining amino acid availability during severe energy restriction.

Despite its efficacy, PSMF induces significant metabolic, endocrine, and cardiovascular adaptation, including adaptive thermogenesis, electrolyte shifts, and hormonal suppression⁴, ⁵, ⁶, ⁷. These effects require structured implementation, particularly around protein intake, electrolytes, and monitoring.

Contraindications

Do Not Use PSMF If

• Pregnancy or lactation
• Kidney, liver, or cardiovascular disease
• Eating disorder history
• Unmonitored metabolic medication use
• Inability to track hydration/electrolytes⁸, ⁷, ⁹

Physiological Basis

PSMF operates through three core mechanisms:

• Severe energy deficit — forces reliance on stored fat for energy¹⁰, ¹¹, ¹²
• Protein preservation signal — adequate dietary protein reduces muscle protein breakdown¹³, ¹⁴
• Controlled ketosis — low carbohydrate availability induces nutritional ketosis as an alternative fuel system¹⁵

Adaptive Counter-Regulation

The body responds with predictable counter-adaptations:

• Reduced resting metabolic rate (adaptive thermogenesis)⁴, ¹⁶
• Hormonal suppression (leptin, T3, testosterone)⁶, ¹⁷
• Increased hunger signaling¹⁸

These adaptations progressively reduce fat loss efficiency over time¹⁹.

Fat Loss Dynamics

Weight loss in PSMF occurs in three distinct phases:

Phase 1 — Water and glycogen (days 0–7):

• Glycogen stores are depleted (~400–500 g), releasing ~1.5–2 kg of bound water²⁰
• Ketosis onset triggers natriuresis (sodium and water excretion)¹⁵, ²¹
• Scale weight drops rapidly — mostly non-fat mass
• Visceral fat mobilization begins preferentially due to its higher lipolytic sensitivity²², ²³

Phase 2 — Accelerated fat loss (weeks 1–4):

• Fat oxidation dominates energy supply
• Obese individuals can expect ~0.2–0.4 kg fat/day²⁰, ¹²
• Visceral fat continues to be lost disproportionately — individuals with central obesity see the largest waist circumference reductions in this phase²⁴, ²²
• Subcutaneous fat mobilization begins but is slower, especially in lower-body depots²⁵, ²⁶
• Adaptive thermogenesis begins to reduce metabolic rate⁴

Phase 3 — Diminishing returns (weeks 4+):

• Fat loss rate slows as hormonal adaptation (leptin, T3, testosterone) accumulates⁴, ²⁷, ⁶
• Remaining fat loss shifts increasingly toward subcutaneous depots as visceral stores are reduced²⁴
• Lean individuals lose progressively less due to stronger counter-regulation
• This phase defines the practical duration limit of PSMF

Important

Scale weight ≠ fat loss. Phase 1 weight loss is predominantly water. Waist circumference is a more reliable early indicator of actual fat loss than scale weight²².

Visceral vs subcutaneous fat

Not all body fat responds equally to caloric restriction. The two primary fat depots differ in metabolic activity, health impact, and mobilization rate:

• Visceral fat (surrounding internal organs) is more metabolically active, more insulin-sensitive, and more lipolytically responsive to catecholamines²⁸, ²⁶. It is preferentially mobilized during early weight loss and severe energy restriction²³, ²².
• Subcutaneous fat (under the skin) is less metabolically active and more resistant to mobilization, particularly in the lower body (gluteofemoral region)²⁵, ²⁶.

PSMF, as a severe energy deficit protocol, preferentially targets visceral fat in the early phases²², ²⁴. This is clinically significant because visceral fat is the primary driver of metabolic syndrome, insulin resistance, and cardiovascular risk²³, ²⁸.

Practical Implication

Individuals with high visceral fat (central/abdominal obesity) will see the greatest metabolic health improvements from PSMF, even before significant subcutaneous fat loss is visible. Waist circumference is a better early progress indicator than overall body fat percentage²², ²³.

Protein Intake

Protein is the primary lean mass protection mechanism in PSMF²⁹.

Under normal caloric deficit conditions, research supports 1.2–1.6 g/kg body weight for most individuals¹³, ³⁰, ³¹, rising to ~2.2 g/kg lean body mass for lean resistance-trained athletes³², ³³. However, these figures come from moderate deficit studies — not the severe restriction seen in PSMF.

Nitrogen balance during PSMF

Nitrogen balance research specific to PSMF and fasting protocols paints a different picture. During severe energy restriction, the body’s protein requirements for maintaining nitrogen equilibrium are lower than general athletic recommendations suggest:

• Hoffer et al. demonstrated that nitrogen equilibrium during VLCD could be achieved at approximately 1.0 g/kg body weight, with higher intakes providing no further nitrogen-sparing benefit³⁴.
• Bistrian’s original PSMF protocol targeted ~1.5 g/kg ideal body weight, based on nitrogen balance data showing this was sufficient to minimize lean mass loss².
• Vazquez & Adibi found that ketogenic VLCDs achieved better nitrogen balance than isocaloric non-ketogenic diets at the same protein intake, suggesting that the ketosis induced by PSMF itself has a protein-sparing effect³⁵.
• Fisler et al. confirmed nitrogen economy improves during sustained VLCD, with the body adapting to conserve nitrogen over time³⁶.
• Winterer et al. used isotope-labeled nitrogen tracers to show that whole-body protein turnover decreases during protein-supplemented fasting, reducing the actual protein requirement³⁷.

Key Takeaway

Nitrogen balance research suggests ~1.0 g/kg body weight is sufficient during PSMF for most individuals. Higher intakes do not meaningfully improve nitrogen retention during severe energy restriction. The ketogenic state itself provides additional protein-sparing effects³⁵, ³⁴.

Key Constraint

Muscle protein synthesis is saturable — once stimulated, additional protein provides diminishing returns¹⁴. In PSMF, protein prevents loss (anti-catabolic role) but does NOT significantly increase muscle gain¹⁴, ³⁸.

Practical protein scaling

BMI	Protein strategy
< 25	~1.0 g/kg body weight
> 25	Decrease by 0.03 g/kg body weight per BMI point above 25

This reflects differences in lean mass proportion³¹, ³³.

Food Selection

Diet composition is designed for:

• Maximal protein density
• Minimal energy intake
• Minimal insulin load

Typical foods:

• Lean poultry
• White fish
• Egg whites
• Low-fat dairy
• Protein isolates

This aligns with clinical VLCD formulations used in obesity treatment¹, ², ³.

Electrolytes and Hydration

Electrolyte disruption is one of the most important risks in PSMF. Glycogen depletion causes water loss, reduced insulin drives sodium excretion, and ketosis triggers natriuresis and fluid shifts²¹, ¹⁵.

Key Risks

• Hypokalemia → arrhythmia risk³⁹
• Hyponatremia → neurological symptoms⁵
• Hypomagnesemia → neuromuscular dysfunction

Recommended daily intake

Electrolyte	Amount
Sodium	1.5–2 g
Potassium	700–900 mg
Magnesium	400–500 mg
Calcium	1–1.2 g40

Electrolyte management is a core safety requirement in VLCD protocols⁴¹, ⁸.

Exercise During PSMF

Resistance training serves muscle preservation, not progression³⁸, ⁴².

Constraints:

• Reduced glycogen availability
• Impaired recovery capacity
• Lower training volume tolerance⁴

Recommended:

• 2–3 sessions/week
• Moderate intensity
• Maintenance focus only

Cardio should be low-intensity steady state to support fat oxidation while minimizing systemic stress. High-intensity training increases recovery burden and is generally discouraged in deep deficit states⁷.

Hormonal and Metabolic Adaptation

PSMF triggers predictable endocrine adaptations as part of adaptive thermogenesis, a conserved survival mechanism⁴, ¹⁶.

Endocrine Shifts

• ↓ Leptin → reduced energy signaling⁶
• ↓ T3 thyroid hormone → lower metabolic rate¹⁷
• ↓ Testosterone (men) → reduced anabolic signaling⁴³, ⁴⁴, ⁴⁵
• ↑ Cortisol → catabolic stress response⁴⁶, ⁴⁷

Cortisol

Severe caloric restriction reliably elevates cortisol, the primary glucocorticoid stress hormone⁴⁶. This is a direct HPA-axis response to energy deprivation and serves to mobilize glucose via gluconeogenesis — partly from muscle protein⁴⁷.

Elevated cortisol during PSMF:

• Increases muscle protein breakdown (opposing the protein-sparing goal)⁴⁸
• Promotes visceral fat retention and water retention⁴⁹
• Impairs immune function and wound healing
• Worsens sleep quality, creating a feedback loop⁵⁰

Cortisol typically peaks in the first 1–2 weeks and partially normalizes as the body adapts, but remains above baseline throughout severe restriction⁴⁶, ⁴⁷.

Sleep

PSMF disrupts sleep through multiple mechanisms⁵¹, ⁵²:

• Low carbohydrate intake reduces serotonin precursor (tryptophan) availability, impairing melatonin synthesis⁵³
• Elevated cortisol suppresses slow-wave (deep) sleep⁵⁰
• Hunger and catecholamine elevation increase nocturnal arousal
• Electrolyte imbalances (especially magnesium) worsen sleep architecture⁵⁴

Sleep-Cortisol Feedback Loop

Poor sleep further elevates cortisol⁵⁰, which further disrupts sleep. This vicious cycle accelerates lean mass loss and impairs recovery. Prioritizing sleep hygiene is a critical — and often overlooked — component of PSMF success.

Practical sleep measures during PSMF:

• No caffeine past 15:00
• Magnesium supplementation in the evening
• Consistent sleep/wake schedule
• Cool, dark sleep environment

Cardiovascular and Clinical Risks

Clinical Risks

• Arrhythmias from potassium imbalance⁵, ³⁹
• Hypotension from reduced blood volume, orthostatic dizziness
• Hypoglycemia risk in medicated individuals⁸

Ketosis vs Ketoacidosis

PSMF induces nutritional ketosis, a regulated metabolic state¹⁵, ⁵⁵, ⁵⁶.

Key Distinction

• Ketosis = adaptive, insulin-present
• Ketoacidosis = pathological, insulin-deficient

PSMF is safe in healthy individuals but requires caution in metabolic disease.

Gallstones and Rapid Weight Loss

Rapid fat loss increases gallstone risk through increased cholesterol saturation in bile and reduced gallbladder motility⁵⁷, ⁵⁸. This is a well-established VLCD complication⁵⁹.

Stimulants

Optional — Only When No Contraindications Are Present

The following stimulants may be used alongside PSMF under appropriate supervision.

Caffeine increases thermogenesis⁶⁰ and improves alertness and adherence⁶¹, ⁶², but carries risks of sleep disruption and cardiovascular stimulation⁶³.

• 1–3× daily, 50–100 mg per dose
• All doses between wake-up and 15:00 — no caffeine past 15:00

Caffeine and Cortisol

Caffeine stimulates the HPA axis and elevates cortisol⁶⁴, ⁶⁵. During PSMF, cortisol is already elevated from caloric restriction⁴⁶. Excessive caffeine compounds this effect, increasing muscle protein breakdown risk and worsening sleep quality. Keep doses moderate and avoid stacking with other stimulants.

Do Not Use DNP

2,4-Dinitrophenol (DNP) is a mitochondrial uncoupler that increases thermogenesis by dissipating the proton gradient as heat⁶⁶. While it accelerates fat loss, it has an extremely narrow therapeutic index — the difference between an effective dose and a lethal dose is small and unpredictable⁶⁷.

• No antidote exists for overdose
• Hyperthermia can be fatal and is dose-dependent
• Cumulative toxicity increases with duration of use
• Combined with PSMF (already metabolically stressed state), risk of adverse events is amplified

DNP is not safely usable for the duration required by a PSMF cycle⁶⁶, ⁶⁷.

Pharmacology

Optional — Only When No Contraindications Are Present

The following agents may be used alongside PSMF under appropriate supervision.

Anabolic steroids — use one of the following (not both) to reduce lean mass loss⁴³, ⁴⁴:

• Oxandrolone (Anavar):
  • Men: 20 mg/day, split into two doses
  • Women: 2.5–5 mg/day, split into two doses when reasonably possible
• Methandrostenolone (Dianabol):
  • 5 mg/day (single dose)

Testosterone Suppression in Context

At the low doses listed above, endogenous testosterone suppression from oxandrolone or methandrostenolone is minimal⁶⁸, ⁶⁹. Severe caloric restriction itself already significantly suppresses testosterone via the HPG axis⁷⁰, ⁶ — the additional suppression from low-dose anabolics is small relative to the deficit-induced suppression already present during PSMF.

Anabolic Steroid Risks

• Hepatotoxicity (especially 17α-alkylated compounds like dianabol)
• Dyslipidemia
• Endocrine suppression
• Cardiovascular remodeling risk⁴⁵
• Women: monitor for virilization

Clinical risk is significant and dose-dependent⁷¹.

Retatrutide (GLP-1/GIP/glucagon triple agonist) may support appetite suppression and metabolic signaling during PSMF.

• Start at 1 mg for the first 5 weeks
• Increase by 1 mg every 5 weeks as needed
• Do not increase when side effects are significant

Retatrutide Risks

• Nausea, vomiting, and diarrhea (common, dose-dependent)
• Pancreatitis risk (rare but serious)
• Gallbladder events — compounded by the already elevated gallstone risk from rapid fat loss⁵⁷
• Long-term safety data is limited — retatrutide remains investigational

Is Retatrutide Necessary?

PSMF itself naturally improves hunger signaling over time. After the initial 3–5 days, ketosis suppresses appetite via elevated ketone bodies and reduced ghrelin¹⁸, ¹⁵. Many individuals find hunger manageable without pharmacological intervention once ketosis is established. Retatrutide adds cost, side effects, and complexity — consider whether the appetite benefit justifies these trade-offs for your situation.

Creatine monohydrate supports training performance and lean mass retention during energy restriction⁷², ⁷³.

• 3–5 g/day, no loading phase required
• Maintains intramuscular phosphocreatine stores despite reduced caloric intake⁷⁴
• May attenuate strength loss during PSMF by preserving high-intensity work capacity⁷²
• Causes ~1–2 kg water retention in muscle (not fat) — do not misinterpret scale weight⁷⁴

Creatine and Scale Weight

Creatine draws water into muscle cells. This is intracellular water, not edema or fat. Expect a small scale increase when starting creatine during PSMF — this is a positive signal of muscle hydration, not fat gain.

Duration and Recovery

Maximum duration

PSMF should be run for 4–8 weeks maximum per cycle¹⁹, ⁹. Beyond this window:

• Adaptive thermogenesis significantly reduces fat loss efficiency⁴, ²⁷
• Hormonal suppression (leptin, T3, testosterone) becomes progressively harder to tolerate⁶, ¹⁷
• Lean mass loss risk increases despite adequate protein³⁸
• Psychological fatigue and adherence failure rise sharply¹⁸

Do Not Extend Beyond 8 Weeks

Clinical VLCD protocols consistently limit continuous use to this range. Longer durations increase risk without proportional benefit¹⁹, ⁹.

Recovery phase

After each PSMF cycle, take a minimum 4-week recovery period at your new maintenance calories (not pre-diet maintenance).

The recovery phase serves to:

• Allow hormonal axes (leptin, thyroid, HPG) to partially normalize⁶, ⁷⁵
• Reverse some adaptive thermogenesis by restoring energy availability⁴, ⁷⁶
• Stabilize new body weight set point before further intervention
• Restore glycogen, hydration, and electrolyte balance
• Recover training capacity and sleep quality

New Maintenance, Not Old Maintenance

Your maintenance calories are lower after fat loss due to reduced body mass and metabolic adaptation. Calculate new maintenance based on current weight and activity, not pre-PSMF values. Eating at old maintenance will cause rapid fat regain¹⁰, ⁷⁵.

Cycling

If further fat loss is needed, repeat: 4–8 weeks PSMF → 4 weeks recovery → reassess. Each subsequent cycle will typically produce less fat loss than the previous one⁷⁶.

Monitoring Protocol

Daily

• Fasted body weight
• Hydration status
• Subjective symptoms

Weekly

• Blood pressure
• Electrolyte status (if available)

Stop or Reassess If

• Palpitations
• Severe dizziness
• Cognitive impairment
• Persistent fatigue

Implementation Summary

Phase 1: Setup

• Calculate protein target
• Prepare lean protein sources
• Establish electrolyte intake
• Review contraindications

Phase 2: Execution

• Maintain protein intake
• Strict electrolyte adherence
• Resistance training 2–3×/week, maintenance only
• Low-intensity cardio only — no high-intensity work
• Apply stimulants and pharmacology if appropriate

Phase 3: Monitoring

• Follow monitoring protocol (daily weight, weekly BP/electrolytes)
• Track symptoms + weight trends
• Watch for hormonal adaptation signs
• Adjust based on tolerance
• Stop after 4–8 weeks — do not extend beyond this window

Phase 4: Recovery

• Transition to new maintenance calories for minimum 4 weeks
• Recalculate maintenance based on current weight
• Restore normal training volume gradually
• Reassess body composition before considering another cycle

Key Takeaways

Summary

• PSMF is highly effective but physiologically demanding
• Early weight loss is largely water and glycogen²⁰, ¹¹
• Protein requirements are moderate, not extreme¹³, ³⁰, ¹⁴
• Electrolytes are a safety-critical component⁵, ³⁹
• Hormonal adaptation limits sustained fat loss speed⁴, ⁶
• PSMF is best understood as a short-term clinical intervention, not a lifestyle diet

Footnotes

1. Blackburn GL et al. (1973). Very low calorie protein-sparing modified fast. Annals of Internal Medicine. https://pubmed.ncbi.nlm.nih.gov/4747064/ ↩ ↩²

2. Bistrian BR et al. (1976). Metabolic effects of PSMF. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/29.5.517 ↩ ↩² ↩³

3. Drenick EJ et al. (1969). VLCD obesity treatment outcomes. New England Journal of Medicine. https://doi.org/10.1056/NEJM196909252811303 ↩ ↩²

4. Müller MJ et al. (2015). Adaptive thermogenesis in humans. Obesity Reviews. https://doi.org/10.1111/obr.12263 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹

5. Sterns RH (2015). Disorders of sodium balance. New England Journal of Medicine. https://doi.org/10.1056/NEJMra1404489 ↩ ↩² ↩³ ↩⁴

6. Rosenbaum M et al. (2008). Leptin and metabolic adaptation. Journal of Clinical Investigation. https://doi.org/10.1172/JCI34294 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸

7. Faria SL et al. (2012). VLCD cardiovascular effects. Obesity Reviews. https://doi.org/10.1111/j.1467-789X.2011.00926.x ↩ ↩² ↩³

8. NICE (2014). Obesity management guidelines (VLCD safety). https://www.nice.org.uk/guidance/cg189 ↩ ↩² ↩³

9. Anderson JW et al. (1992). VLCD safety long-term. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/56.1.229 ↩ ↩² ↩³

10. Hall KD et al. (2016). Energy balance regulation. American Journal of Clinical Nutrition. https://doi.org/10.3945/ajcn.115.110486 ↩ ↩²

11. Thomas DM et al. (2013). Weight loss dynamics. International Journal of Obesity. https://doi.org/10.1038/ijo.2013.59 ↩ ↩²

12. Hall KD et al. (2012). Fat loss rate modeling. Obesity. https://doi.org/10.1038/oby.2011.345 ↩ ↩²

13. Morton RW et al. (2018). A systematic review, meta-analysis and meta-regression of protein supplementation and resistance training. British Journal of Sports Medicine. https://bjsm.bmj.com/content/52/6/376 ↩ ↩² ↩³

14. Moore DR (2019). Muscle protein synthesis regulation. Applied Physiology, Nutrition, and Metabolism. https://doi.org/10.1139/apnm-2018-0191 ↩ ↩² ↩³ ↩⁴

15. Cahill GF (2006). Starvation metabolism and ketosis. Annual Review of Nutrition. https://doi.org/10.1146/annurev.nutr.26.061505.111258 ↩ ↩² ↩³ ↩⁴ ↩⁵

16. Müller MJ & Bosy-Westphal A (2013). Adaptive thermogenesis mechanisms. Obesity Reviews. https://doi.org/10.1111/obr.12047 ↩ ↩²

17. Tappy L (2004). Hormonal energy regulation. European Journal of Clinical Nutrition. https://doi.org/10.1038/sj.ejcn.1601951 ↩ ↩² ↩³

18. Sumithran P & Proietto J (2013). Weight regain biology. Lancet Diabetes & Endocrinology. https://doi.org/10.1016/S2213-8587(13)70062-3 ↩ ↩² ↩³

19. Tsai AG & Wadden TA (2006). VLCD evolution and application. Obesity Research. https://doi.org/10.1038/oby.2006.1 ↩ ↩² ↩³

20. Hall KD (2011). Predicting metabolic adaptation, body weight change, and energy intake in humans. The Lancet. https://doi.org/10.1016/S0140-6736(11)60849-2 ↩ ↩² ↩³

21. Verbalis JG (2010). Fluid balance regulation. American Journal of Medicine. https://doi.org/10.1016/j.amjmed.2009.10.030 ↩ ↩²

22. Ross R et al. (2000). Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-133-2-200007180-00008 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶

23. Després JP & Lemieux I (2006). Abdominal obesity and metabolic syndrome. Nature. https://doi.org/10.1038/nature05488 ↩ ↩² ↩³ ↩⁴

24. Chaston TB & Dixon JB (2008). Factors associated with percent change in visceral versus subcutaneous abdominal fat during weight loss. International Journal of Obesity. https://doi.org/10.1038/sj.ijo.0803661 ↩ ↩² ↩³

25. Karpe F & Pinnick KE (2015). Biology of upper-body and lower-body adipose tissue. Diabetes. https://doi.org/10.2337/db14-1624 ↩ ↩²

26. Ibrahim MM (2010). Subcutaneous and visceral adipose tissue: structural and functional differences. Obesity Reviews. https://doi.org/10.1111/j.1467-789X.2009.00623.x ↩ ↩² ↩³

27. Leibel RL et al. (1995). Energy expenditure adaptation. New England Journal of Medicine. https://doi.org/10.1056/NEJM199503093321001 ↩ ↩²

28. Wajchenberg BL (2000). Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocrine Reviews. https://doi.org/10.1210/edrv.21.6.0415 ↩ ↩²

29. Phillips SM & Van Loon LJC (2011). Dietary protein for athletes. Journal of Sports Sciences. https://doi.org/10.1080/02640414.2011.619204 ↩

30. Phillips SM (2014). Higher protein diets in weight loss. Sports Medicine. https://doi.org/10.1007/s40279-014-0247-4 ↩ ↩²

31. Jäger R et al. (2017). ISSN position stand: protein and exercise. JISSN. https://jissn.biomedcentral.com/articles/10.1186/s12970-017-0177-8 ↩ ↩²

32. Helms ER et al. (2014). Evidence-based recommendations for natural bodybuilding contest preparation. Journal of the International Society of Sports Nutrition. https://jissn.biomedcentral.com/articles/10.1186/1550-2783-11-20 ↩

33. Witard OC et al. (2019). Protein intake and skeletal muscle mass. Nutrients. https://doi.org/10.3390/nu11010006 ↩ ↩²

34. Hoffer LJ et al. (1984). Metabolic effects of very low calorie weight reduction diets. Journal of Clinical Investigation. https://doi.org/10.1172/JCI111516 ↩ ↩²

35. Vazquez JA & Adibi SA (1992). Protein sparing during treatment of obesity: ketogenic versus nonketogenic very low calorie diet. Metabolism. https://doi.org/10.1016/0026-0495(92)90023-4 ↩ ↩²

36. Fisler JS et al. (1982). Nitrogen economy during very low calorie diets: quality and quantity of dietary protein. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/35.3.471 ↩

37. Winterer JC et al. (1980). Whole body protein turnover, studied with 15N-glycine, and muscle protein breakdown in mildly obese subjects during a protein-sparing diet and a brief total fast. Metabolism. https://doi.org/10.1016/0026-0495(80)90100-6 ↩

38. Mettler S et al. (2010). Protein intake during energy deficit training. Medicine & Science in Sports & Exercise. https://doi.org/10.1249/MSS.0b013e3181cc749e ↩ ↩² ↩³

39. Gennari FJ (1998). Hypokalemia physiology. New England Journal of Medicine. https://doi.org/10.1056/NEJM199803263381307 ↩ ↩² ↩³

40. Institute of Medicine (2005). Dietary reference intakes for electrolytes. National Academies Press. ↩

41. Gibson AA et al. (2015). Very low energy diets and metabolic effects. Nutrients. https://pmc.ncbi.nlm.nih.gov/articles/PMC4784653 ↩

42. Garthe I et al. (2011). Body composition during diet and training. International Journal of Sport Nutrition and Exercise Metabolism. https://doi.org/10.1123/ijsnem.21.2.87 ↩

43. Hartgens F & Kuipers H (2004). Anabolic steroids effects. Sports Medicine. https://doi.org/10.2165/00007256-200434080-00003 ↩ ↩²

44. Bhasin S et al. (1996). Testosterone dose response. New England Journal of Medicine. https://doi.org/10.1056/NEJM199607043350101 ↩ ↩²

45. Basaria S et al. (2010). Steroid abuse consequences. Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jc.2009-2508 ↩ ↩²

46. Tomiyama AJ et al. (2010). Low calorie dieting increases cortisol. Psychosomatic Medicine. https://doi.org/10.1097/PSY.0b013e3181d9523c ↩ ↩² ↩³ ↩⁴

47. Fichter MM & Pirke KM (1986). Effect of experimental and pathological weight loss upon the hypothalamo-pituitary-adrenal axis. Psychoneuroendocrinology. https://doi.org/10.1016/0306-4530(86)90046-6 ↩ ↩² ↩³

48. Simmons PS et al. (2016). Increased proteolysis: effect of cortisol on amino acid metabolism. Journal of Clinical Investigation. https://doi.org/10.1172/JCI111482 ↩

49. Epel ES et al. (2001). Stress and body shape: cortisol and abdominal fat. Psychosomatic Medicine. https://doi.org/10.1097/00006842-200109000-00002 ↩

50. Leproult R et al. (1997). Sleep loss results in elevation of cortisol levels the next evening. Sleep. https://doi.org/10.1093/sleep/20.10.865 ↩ ↩² ↩³

51. Kilkus JM et al. (2007). Caloric restriction and sleep. Sleep. https://doi.org/10.1093/sleep/30.6.735 ↩

52. Afaghi A et al. (2007). High-glycemic-index carbohydrate meals shorten sleep onset. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/85.2.426 ↩

53. Wurtman RJ & Wurtman JJ (2003). Carbohydrates and serotonin synthesis. In: Fernstrom JD, ed. Nutritional Neuroscience. https://doi.org/10.1016/S0899-9007(03)00056-9 ↩

54. Held K et al. (2002). Oral magnesium supplementation reverses age-related neuroendocrine and sleep EEG changes. Pharmacopsychiatry. https://doi.org/10.1055/s-2002-33195 ↩

55. Jeejeebhoy KN (2000). Starvation physiology and clinical nutrition. Clinical Nutrition. https://doi.org/10.1054/clnu.1999.0078 ↩

56. Cahill GF Jr. Starvation metabolic physiology (Harvard studies). Historical metabolic research corpus. ↩

57. Shiffman ML et al. (1991). Rapid weight loss and gallstones. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-114-7-589 ↩ ↩²

58. Festi D et al. (2009). Gallstone disease mechanisms. World Journal of Gastroenterology. https://doi.org/10.3748/wjg.15.3172 ↩

59. Everhart JE (1993). Gallstones and rapid weight loss. Gastroenterology Clinics of North America. https://pubmed.ncbi.nlm.nih.gov/8365447/ ↩

60. Dulloo AG et al. (1989). Caffeine thermogenesis. American Journal of Physiology. https://doi.org/10.1152/ajpregu.1989.256.2.R341 ↩

61. Astrup A et al. (1990). Caffeine increases energy expenditure. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/51.4.759 ↩

62. Grgic J et al. (2019). Caffeine and performance. British Journal of Sports Medicine. https://doi.org/10.1136/bjsports-2018-100278 ↩

63. Heckman MA et al. (2010). Caffeine metabolism. Journal of Food Science. https://doi.org/10.1111/j.1750-3841.2010.01522.x ↩

64. Lovallo WR et al. (2005). Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women. Pharmacology Biochemistry and Behavior. https://doi.org/10.1016/j.pbb.2005.08.008 ↩

65. Beaudoin MS & Graham TE (2011). Methylxanthines and human health: epidemiological and experimental evidence. Handbook of Experimental Pharmacology. https://doi.org/10.1007/978-3-642-13443-2_19 ↩

66. Grundlingh J et al. (2011). 2,4-Dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death. Journal of Medical Toxicology. https://doi.org/10.1007/s13181-011-0162-6 ↩ ↩²

67. McFee RB et al. (2004). Dying to be thin: a dinitrophenol related fatality. Veterinary and Human Toxicology. https://pubmed.ncbi.nlm.nih.gov/15303393/ ↩ ↩²

68. Berger JR et al. (1996). Oxandrolone in AIDS-wasting myopathy. AIDS. https://doi.org/10.1097/00002030-199612000-00005 ↩

69. Orr R & Fiatarone Singh M (2004). The anabolic androgenic steroid oxandrolone in the treatment of wasting and catabolic disorders. Drugs. https://doi.org/10.2165/00003495-200464070-00004 ↩

70. Cangemi R et al. (2010). Long-term effects of calorie restriction on serum sex-hormone concentrations in men. Aging Cell. https://doi.org/10.1111/j.1474-9726.2010.00553.x ↩

71. Basaria S (2010). Androgen abuse in athletes and consequences. Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jc.2009-2508 ↩

72. Rawson ES & Volek JS (2003). Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. Journal of Strength and Conditioning Research. https://doi.org/10.1519/1533-4287(2003)017%3C0822:EOCSAR%3E2.0.CO;2 ↩ ↩²

73. Branch JD (2003). Effect of creatine supplementation on body composition and performance: a meta-analysis. International Journal of Sport Nutrition and Exercise Metabolism. https://doi.org/10.1123/ijsnem.13.2.198 ↩

74. Kreider RB et al. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation. JISSN. https://doi.org/10.1186/s12970-017-0173-z ↩ ↩²

75. Dulloo AG et al. (2012). How dieting makes the lean fatter: from a perspective of body composition autoregulation through adipostats and proteinstats. Obesity Reviews. https://doi.org/10.1111/j.1467-789X.2011.00941.x ↩ ↩²

76. Trexler ET et al. (2014). Metabolic adaptation to weight loss: implications for the athlete. Journal of the International Society of Sports Nutrition. https://doi.org/10.1186/1550-2783-11-7 ↩ ↩²