LYME LITERATE DOCTORS AND ADVOCATES KNOW

INFECTIONS INFLAME AND MOST PATIENTS GAIN WEIGHT

Here are 100 causes and contributors to weight gain, covering increased body fat, fluid retention, and other increases in body mass.

No scientifically established ranking of 100 causes exists. This list places common contributors first, followed by medications, medical conditions, and uncommon genetic disorders. Several overlap, and some are risk factors rather than independent causes. References are collected at the end.

Food intake and eating patterns — 1–20

These factors can increase energy intake beyond the body’s requirements. Their effects depend on the overall diet and individual circumstances. [1–4]

1. Large portions—more calories per meal.
2. Sugar-sweetened drinks—soda, sweetened tea, and similar beverages.
3. Calorie-dense coffee drinks—syrups, cream, and added sugar.
4. Frequent alcohol consumption—additional calories, sometimes accompanied by increased eating.
5. Diets dominated by ultra-processed foods—some promote greater spontaneous calorie intake.
6. Frequent fast-food meals—often large and calorie dense.
7. Frequent fried foods—added oil increases energy density.
8. Frequent sweets and desserts—especially when added to usual meals.
9. Unmeasured oils, butter, dressings, and sauces—easily overlooked calories.
10. Frequent snacking without compensating at meals.
11. Grazing throughout the day—repeated small amounts can accumulate.
12. Eating while watching television or using screens—may reduce awareness of intake.
13. Rapid eating—can make it easier to eat beyond fullness.
14. Emotional eating—using food to manage distress.
15. Boredom-driven eating.
16. Eating in response to food cues rather than hunger—availability, advertising, or social settings.
17. Low-fiber eating patterns—may provide less fullness.
18. Insufficient dietary protein—can reduce satiety in some people.
19. Calorie-containing supplements or meal replacements added to regular meals.
20. Overestimating calories burned during exercise and eating more to compensate.

Activity, sleep, environment, and weight-regulation changes — 21–40

These contributors affect energy expenditure, appetite, or access to food and activity. They do not produce weight gain in everyone. [1–3,5–7]

21. Stopping or reducing regular exercise.
22. A sedentary occupation.
23. Prolonged recreational sitting.
24. Less everyday movement—walking, errands, housework, and standing.
25. Injury-related immobility.
26. Chronic pain that limits movement.
27. Disability or neurological disease that reduces mobility.
28. Prolonged bed rest or recovery after surgery.
29. Age-related muscle loss—can lower energy requirements.
30. Retirement or another routine change that reduces activity.
31. Chronic insufficient sleep.
32. Shift work and circadian disruption—associated with increased obesity risk.
33. Chronic stress—may alter appetite, sleep, and eating.
34. Limited access to affordable, nutritious food.
35. Food insecurity—can contribute through unstable food access and reliance on inexpensive, energy-dense foods.
36. Lack of safe or accessible places for physical activity.
37. Smoking cessation—appetite and energy expenditure change; quitting still provides major health benefits.
38. Increased hunger after weight loss—a biological driver of regain.
39. Reduced energy expenditure after weight loss—including a smaller body and, sometimes, adaptive thermogenesis.
40. Stopping an effective weight-management medication—appetite may return and weight may be regained.

Medication-related causes — 41–70

Risk varies by drug, dose, duration, and patient. Some medicines increase appetite or fat mass; others mainly cause fluid retention. Do not discontinue prescribed treatment without discussing alternatives with the prescriber. [8–10]

41. Systemic glucocorticoids—prednisone, prednisolone, dexamethasone.
42. Olanzapine.
43. Clozapine.
44. Quetiapine.
45. Risperidone or paliperidone.
46. Mirtazapine.
47. Tricyclic antidepressants—such as amitriptyline.
48. Paroxetine—particularly with longer use.
49. Phenelzine—a monoamine oxidase inhibitor antidepressant.
50. Lithium.
51. Valproate or divalproex.
52. Carbamazepine—in some patients.
53. Gabapentin.
54. Pregabalin.
55. Insulin.
56. Sulfonylureas—such as glipizide, glimepiride, and glyburide.
57. Meglitinides—such as repaglinide.
58. Pioglitazone or rosiglitazone—fat gain and fluid retention.
59. Some beta-blockers—such as metoprolol.
60. Depot medroxyprogesterone acetate contraceptive injections.
61. Megestrol acetate—a strong appetite stimulant.
62. Cyproheptadine—an antihistamine with appetite-stimulating effects.
63. Some other H1 antihistamines—weight effects vary, and evidence is less definitive.
64. Some HIV antiretroviral regimens—including certain integrase inhibitor–based combinations.
65. Androgen-deprivation therapy—can increase fat and reduce muscle.
66. Amlodipine and related calcium-channel blockers—primarily swelling.
67. Nonsteroidal anti-inflammatory drugs—such as ibuprofen; primarily fluid retention.
68. Fludrocortisone—sodium and water retention.
69. Minoxidil taken orally—can cause fluid retention.
70. Pramipexole or ropinirole—occasionally through compulsive eating.

Hormonal, psychiatric, neurological, and genetic causes — 71–90

Some primarily increase appetite or body fat; others change body composition. Rare disorders are especially relevant when obesity begins very early, is severe, or accompanies unusual developmental or endocrine findings. [1,3,11–14]

71. Hypothyroidism—usually modest gain, partly from retained salt and water.
72. Endogenous Cushing syndrome—excess cortisol from pituitary, adrenal, or other sources.
73. Polycystic ovary syndrome—can predispose to weight gain; the relationship is bidirectional.
74. Menopause-related changes—favor abdominal fat accumulation; aging and activity also influence total weight.
75. Male hypogonadism—can increase fat and reduce lean mass.
76. Adult growth hormone deficiency—can increase fat mass.
77. Insulinoma—recurrent hypoglycemia may lead to frequent eating.
78. Hypothalamic injury from a tumor—especially craniopharyngioma.
79. Hypothalamic injury after brain surgery or radiation.
80. Traumatic brain injury affecting appetite regulation or pituitary function.
81. Binge-eating disorder.
82. Depression with increased appetite—particularly atypical features.
83. Night-eating syndrome—may contribute through additional food intake.
84. Sleep-related eating disorder—eating during partial arousals from sleep.
85. Common polygenic susceptibility—many genetic variants influence hunger and weight regulation.
86. Prader–Willi syndrome.
87. Melanocortin-4 receptor deficiency.
88. Congenital leptin deficiency.
89. Leptin receptor deficiency.
90. Bardet–Biedl syndrome.

Fluid retention and other increases on the scale — 91–100

These can raise body weight without an equivalent increase in body fat. [15–17]

91. Heart failure—fluid accumulation.
92. Acute kidney injury or advanced chronic kidney disease—impaired fluid excretion.
93. Nephrotic syndrome—urinary protein loss and edema.
94. Cirrhosis with ascites or peripheral edema.
95. Severe hypoalbuminemia from protein-losing enteropathy or malnutrition—edema may mask tissue loss.
96. Pregnancy—fetal, placental, blood-volume, fluid, and maternal tissue increases.
97. Preeclampsia—can cause sudden fluid-related weight gain during pregnancy or postpartum.
98. Menstrual-cycle–related fluid retention—usually temporary.
99. Glycogen replenishment after carbohydrate restriction—stored glycogen carries water.
100. Muscle gain from resistance training—a potentially healthy increase in body mass.

Rapid weight gain over days, particularly with shortness of breath, reduced urination, or substantial swelling, needs prompt medical assessment. Sudden swelling with headache or visual symptoms during pregnancy also warrants urgent evaluation. [15–17]

References

1. National Institute of Diabetes and Digestive and Kidney Diseases. Factors Affecting Weight & Health. Reviewed May 2023. National Institutes of Health.
2. National Heart, Lung, and Blood Institute. Overweight and Obesity: Causes and Risk Factors. National Institutes of Health.
3. van der Valk ES, van den Akker ELT, Savas M, et al. A comprehensive diagnostic approach to detect underlying causes of obesity in adults. Obesity Reviews. 2019;20(6):795–804. doi:10.1111/obr.12836.
4. Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metabolism. 2019;30(1):67–77.e3. doi:10.1016/j.cmet.2019.05.008.
5. Covassin N, Singh P, McCrady-Spitzer SK, et al. Effects of experimental sleep restriction on energy intake, energy expenditure, and visceral obesity. Journal of the American College of Cardiology. 2022;79(13):1254–1265. doi:10.1016/j.jacc.2022.01.038.
6. Aubin HJ, Farley A, Lycett D, Lahmek P, Aveyard P. Weight gain in smokers after quitting cigarettes: meta-analysis. BMJ. 2012;345:e4439. doi:10.1136/bmj.e4439.
7. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism. 2022;24(8):1553–1564. doi:10.1111/dom.14725.
8. Drugs That Affect Body Weight, Body Fat Distribution, and Metabolism. In: Endotext. South Dartmouth, MA: MDText.com, Inc. Available through NCBI Bookshelf.
9. Domecq JP, Prutsky G, Leppin A, et al. Drugs commonly associated with weight change: a systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism. 2015;100(2):363–370. doi:10.1210/jc.2014-3421.
10. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology & Metabolism. 2015;100(2):342–362. doi:10.1210/jc.2014-3415.
11. American Thyroid Association. Thyroid and Weight. Patient education brochure.
12. National Institute of Diabetes and Digestive and Kidney Diseases. Cushing’s Syndrome. National Institutes of Health.
13. Driscoll DJ, Miller JL, Cassidy SB. Prader-Willi Syndrome. In: GeneReviews®. Seattle, WA: University of Washington, Seattle. Updated 2026.
14. Body Weight Regulation. In: Endotext. South Dartmouth, MA: MDText.com, Inc. Available through NCBI Bookshelf.
15. Merck Manual Professional Edition. Edema. Clinical reference covering cardiac, renal, hepatic, medication-related, and other causes of fluid accumulation.
16. National Library of Medicine. Weight gain—unintentional. MedlinePlus Medical Encyclopedia.
17. National Library of Medicine. Edema. MedlinePlus.