Prednisone is a synthetic pregnane corticosteroid that was first identified in 1950 by the American microbiologist Arthur Nobile, and thereafter, synthesized in 1955 by the Schering Corporation. As a synthetic derivative of cortisone, prednisone acts by mimicking the physiologic effects of cortisol, the chief endogenous hormone secreted by the adrenal cortex when the body is under physical or psychological stress.
Its potent action as a corticosteroid alters DNA signaling, modulates immune function, and enables prednisone to aid in the management of autoimmune diseases, inflammatory diseases, and specific types of cancer. Examples of medical conditions that might be treated with prednisone include: adrenocortical insufficiency, asthma, COPD, Chron’s disease, CIPD, rheumatoid arthritis, multiple sclerosis, sarcoidosis, thyroiditis, and ulcerative colitis.
Although prednisone is an extremely useful medication for treating serious and potentially life-threatening medical conditions, it often causes harsh and unwanted side effects. One side effect that many prospective prednisone users are concerned with is weight gain. Prospective prednisone users want to know whether the medication will cause weight gain, and if so, the average amount they should expect.
Prednisone & Weight Gain (Why It Occurs)
Although not all prednisone users will experience clinically significant weight gain during treatment, many users will report weight gain as a side effect. Data from a majority of randomized controlled trials indicate that weight gain is one of the most common side effects of prednisone treatment.
If you gain a significant amount of weight while using prednisone, below are some possible reasons as to why the weight gain might’ve occurred. Understand that the specific cause(s) of one person’s weight gain on prednisone may differ from the cause(s) of another user’s weight gain.
Appetite increase: Although prednisone users may experience weight gain during treatment irrespective of increased appetite, many individuals who gain weight on prednisone directly attribute their weight gain to an unexpected surge or spike in appetite. Increased appetite and/or hunger is a known side effect of prednisone that may be difficult for some individuals to manage.
Research by Chrousos et al. (2011) noted that appetite enhancement is an unavoidable side effect of glucocorticoids (like prednisone) even early in therapy. Furthermore, a study by Patel et al. (2018) documented “increased appetite” in 7.5% of self-reports among patients using prednisone – making it the third most common reaction (after weight gain and insomnia).
If you constantly feel ravenous [or hungrier than you did before using prednisone], there’s a good chance that you’ll end up consuming more calories than usual. Consuming a greater number of total calories per day than pre-treatment may put your body in a hypercaloric state such that you experience weight gain.
Bloating: Prednisone sometimes causes significant bloating or edema as a side effect by altering electrolyte levels. Specifically, the bloating experienced by prednisone users is hypothesized to result from increased sodium (salt) retention and decreased potassium retention. If you experience increased bloating while using prednisone and notice weight gain, there’s a chance that some of your weight gain could be directly attributable to the bloat.
Because your body is carrying more water than it usually does (due to sodium retention), you’ll weigh more when you step on the scale. Though the amount of weight increase as a result of bloating will be subject to individual variation (among prednisone users), it’s reasonable to estimate that excessive bloating could account for several pounds of body weight increase.
Cognitive dysfunction: If cognitive impairment occurs during treatment, it’s reasonable to speculate that this could [indirectly] cause weight gain. Evidence presented by Brown and Chandler (2001) suggests that prednisone (and other corticosteroids) can cause severe cognitive dysfunction – sometimes to extent of dementia or delirium.
Examples of cognitive deficits associated with prednisone (20 mg to 100 mg per day) include: attentional deficits, disorganized thinking, disorientation, poor concentration, and memory reduction. Assuming prednisone causes cognitive dysfunction, this dysfunction may detrimentally affect self-regulation and planning, both of which could indirectly lead to weight gain.
For example, if self-regulation and planning abilities are impaired, it may become difficult to restrain oneself around food (even after feeling full) and/or plan healthy meals. When cognitive dysfunction is paired with other side effects like increased appetite, it may amplify the risk and/or significance of a prednisone user’s weight gain.
Fat storage & muscle loss: A subset of prednisone users who report weight gain may notice increased body fat and simultaneous muscle loss – largely due to the medication. Increases in body fat coupled with muscle loss while using prednisone are probably attributable to: hormone fluctuations, changes in resting metabolic rate, and/or alterations in gut bacteria.
Prednisone causes a reduction in gonadotropin-releasing hormone (GRH) coupled with increased luteinizing hormone which lowers concentrations of estrogen and testosterone (particularly in men). Researchers hypothesize that reduced testosterone levels (as a result of prednisone administration) can induce osteoporosis (bone and muscle loss) along with increased fat storage.
Furthermore, when muscle and/or bone is lost as a result of corticosteroid treatment, the body’s resting metabolic rate decreases. A reduction in resting metabolic rate [attributable to loss of lean mass] causes the body will burn fewer calories than usual which could contribute to weight gain (and detrimental changes in body composition such as fat gain around the stomach).
Evidence to support the idea that prednisone causes increased fat storage and muscle loss is derived from a study by Al-Jaouni et al. (2002). The study reported that prednisone treatment significantly reduced fat metabolism and significantly increased protein oxidation in 29 women with Chron’s disease.
Food cravings: When administering corticosteroids like prednisone, some individuals claim to experience substantial food cravings or feel as though they’ve developed “the munchies.” A subset of anecdotal reports online from prednisone users claim that the medication makes them crave carbohydrates and breakfast foods. Others claim that prednisone causes them to crave hyperpalatable (high-fat, high-sugar, high-salt) “junk foods” throughout treatment.
Because these cravings may be accompanied by other side effects such as increased appetite and diminished cognitive function (possibly self-regulation) – it’s easy to see how food cravings could lead to weight gain. If the cravings are constant, it’ll probably be just a matter of time before you attain the foods that you’re craving – and chow down. Because these cravings may cause you to eat a greater number of calories than usual, they might be a prominent driver of your weight gain on prednisone.
Gastrointestinal & gut bacteria modulation: Using prednisone can modulate gastrointestinal function and concentrations of gut bacteria, each of which could contribute to weight gain. As a result of altering gastrointestinal function, some prednisone users will experience bloating and/or constipation. If you become bloated and/or constipated as a result of prednisone, your body will weigh more than usual due to increased retention of water and/or digested food.
Another potential means by which prednisone may cause weight gain is via modulation of gut bacteria. Research by Gianotti et al. (1996) discovered that prednisone altered concentrations of gut microbes in animal models – opposite that of the endogenous steroid dehydroepiandrosterone (DHEA). Because altering concentrations of gut bacteria can increase appetite and/or cause bloating – it’s possible that prednisone-mediated gut bacteria alterations could lead to weight gain.
Hormonal modulation: As a corticosteroid, prednisone mimics the physiologic effects of the stress hormone cortisol. Its action as a cortisol-mimetic can activate the sympathetic nervous system, downregulate activation of the parasympathetic nervous system, and indirectly modulate concentrations of endogenous hormones secreted within the body.
Research indicates that prednisone can affect hormones like: IGF-1, insulin, DHEA, gonadotropin-releasing hormone, luteinizing hormone, estrogen, and testosterone – especially if used for a long-term. More specifically, prednisone seems to increase IGF-1, insulin (sometimes to the point of “insulin resistance”), and luteinizing hormone – while simultaneously decreasing DHEA, gonadotropin-releasing hormone, estrogen, and testosterone.
The modulation of the aforementioned hormones could account for unfavorable changes in body composition (e.g. greater centripetal fat) and body weight increases throughout treatment. It is also believed that prednisone might induce weight gain by altering levels of adipocyte-derived hormones such as: adiponectin, leptin, and resistin – when used for a long-term.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/25611207
- Source: https://www.ncbi.nlm.nih.gov/pubmed/21635675
- Source: https://www.ncbi.nlm.nih.gov/pubmed/8957747
- Source: https://www.ncbi.nlm.nih.gov/pubmed/16107513
Metabolic changes: Considering that prednisone tends to increase energy levels by activating the sympathetic nervous system, most users probably aren’t exhibiting a slowing of metabolic rate during treatment. What’s more likely is that prednisone is causing weight gain and/or unfavorable changes in body composition via induction of several metabolic changes.
A study by Ellero-Simatos et al. (2012) investigated the metabolic effects of prednisone in healthy adult volunteers and discovered that the medication dose-dependently and time-dependently altered amino acid metabolism. The most prominent finding was that prednisone induced aminoaciduria, a condition characterized by abnormal concentrations of amino acids in the urine.
Other metabolic effects of prednisone include: inhibiting insulin secretion (via inhibiting beta-cell function); inducing protein catabolism; and inhibiting muscle protein synthesis. The combination of metabolic changes occurring in prednisone users (particularly persons taking high-doses for a long-term) might account for weight gain and unfavorable changes in body composition.
Mood changes: Substantial mood changes can occur as adverse reactions to prednisone treatment, including: anxiety, depression, and mania. In the event that you experience major mood changes or other neuropsychiatric symptoms from prednisone such as: insomnia or emotional lability – it’s possible that these could affect your appetite and/or feeding behavior.
More specifically, prednisone-mediated mood changes might increase your appetite, causing you to consume more calories than usual whereby you gain weight. Another possibility is that prednisone-mediated mood changes might lead certain users to consume food as a coping mechanism (in attempt to decrease stress and/or negative emotion) such that they end up experiencing weight gain.
Reversal of disease activity: Because prednisone is prescribed to treat many autoimmune and inflammatory conditions in which weight loss is a prominent feature, one reason that some patients might gain a significant amount of weight while using prednisone is due to the reduction of disease activity. In fact, a study by Jurgens et al. (2013) suggested that increases in BMI among patients with rheumatoid arthritis (using adjunct prednisone 10 mg/day with methotrexate) was primarily attributable to reversal of disease activity – rather than a side effect of prednisone.
It is known that autoimmune conditions like rheumatoid arthritis can cause weight loss and cachexia due to excessive secretion of proinflammatory cytokines (e.g. TNF-alpha). In the case of Duchenne muscular dystrophy (DMD), weight loss can occur due to increased activation of the sympathetic nervous system and heat production within brown adipose tissue (BAT) – which amplifies resting metabolic rate and causes weight loss.
Assuming prednisone effectively counteracts a disease that’s causing weight loss, reversal of the diseased state should yield weight gain. Among patients who had lost weight and/or become underweight due to an untreated disease, a majority of weight gain that results from prednisone treatment might be favorable and/or therapeutic.
Note: There could be additional explanations for weight gain on prednisone other than those discussed above. If you know of any additional mechanisms by which prednisone might induce weight gain during treatment, report them in the comments section.
Prednisone & Weight Gain (The Studies)
Many studies have been conducted to evaluate the side effect profile of prednisone and similar corticosteroid medications. Included below are summaries of studies in which the effect of prednisone (or similar glucocorticoids) on body weight was discussed.
As you’ll read, nearly all randomized controlled trials indicate that weight gain is a common side effect of prednisone (and other glucocorticoid medications). Though there are some limitations associated with the studies below, data are nearly unanimous in suggesting that prednisone can cause significant weight gain – regardless of the dosage or length of treatment.
2018: Frequent discussion of insomnia and weight gain with glucocorticoid therapy: an analysis of Twitter posts.
Patel, Belousov, Jani, et al. conducted a study in which data from the social media platform “Twitter” was compiled and analyzed to determine the frequency of side effects associated with glucocorticoid treatment. Researchers used a computerized system that was configured to automatically detect adverse drug reactions via narrative text on Twitter.
After data was compiled from Twitter, the frequency patterns of adverse reactions associated with glucocorticoid treatment was compared to a national drug regulatory library. A total of 159,297 tweets were documented as mentioning either “prednisone” or “prednisolone” between October 2012 and June 2015.
The most frequently-mentioned adverse reactions [on Twitter] associated with glucocorticoid treatment were “weight gain” and “insomnia.” In comparison to spontaneous reports via the UK regulator’s ADR reporting scheme – these adverse reactions were reported substantially more often on Twitter.
This suggests that certain adverse reactions of medications may be underreported by patients in formalized settings. An in-depth analysis documented weight gain in 8.2% of tweets and increased appetite in 7.5% of tweets – each of which can go hand-in-hand.
Although the method utilized in this study was an informal way of analyzing side effect data, it supports the idea that prednisone and similar medications cause weight gain. That said, this study is limited by the demographics of Twitter users – making it difficult to know whether these reports accurately reflect adverse reactions in the general population.
2017: Systematic Evaluation of Corticosteroid Use in Obese and Non-obese Individuals: A Multi-cohort Study.
Savas, Wester, Staufenbiel, et al. noted that while corticosteroid use is associated with high rates of weight gain, no studies had ever attempted to determine whether there might be differences in rates of corticosteroid use in obese versus non-obese individuals. For this reason, researchers conducted a study in which data from 274 obese and 526 non-obese controls were compared.
Results of the study indicated that obese individuals exhibited nearly two-fold greater incidence of recent corticosteroid use – compared to non-obese controls. Furthermore, 10.5% of obese individuals reported that the use of corticosteroids (most commonly prednisone) triggered significant weight gain over a long-term (usually exceeding 3 months).
Based on the results of this study, researchers recommend that medical doctors watch for corticosteroid-induced side effects among their patients – particularly weight gain. Moreover, results of this study indicate that weight gain from corticosteroids like prednisone is likely to occur with long-term use; probably due to cumulative exposure.
2017: Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children.
Aljebab, Choonara, and Conroy conducted a systematic review evaluating the toxicity of long-term oral corticosteroid treatment in children. The purpose of the systematic review was to determine the most prevalent and serious side effects of oral corticosteroids in pediatrics.
For the review, researchers collected relevant data from studies published in: Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed. To be included in the review, studies needed to involve: pediatrics (ages 28 days to 18 years) and corticosteroid treatment (for a minimum of 15 days).
A total of 101 studies (33 cohort; 21 RCTs; 21 case series; 26 case reports) met inclusion criteria for the systematic review. These studies encompassed 6817 children and documented 4321 adverse reactions. Weight gain was listed as being among the top adverse reactions reported in children using corticosteroids – occurring in 21.1% of users.
2016: Changes in Body Mass Related to the Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis.
Baker, Sauer, Cannon, et al. sought to investigate how various disease-modifying agents influence body weight and composition among patients with rheumatoid arthritis. For the study, researchers utilized the US Department of Veterans Affairs pharmacy databases to gather data from patients receiving: methotrexate; prednisone; leflunomide; and tumor necrosis factor inhibitors (TNFi).
Levels of C-reactive protein (CRP) and BMI of the patients were recorded (from a time as close to the initiation of treatment as possible) – as well as at a later date (from follow-up appointments). Researchers used regression models to determine BMI changes associated with each disease-modifying agent in comparison to methotrexate – as well as matched-weighting techniques to assess the impact of confounds.
A total of 32,859 patients with rheumatoid arthritis and 52,662 treatment courses were documented. Results indicated that at 6 months from date of initial prescription fill (i.e. treatment initiation), weight gain was observed among patients receiving: methotrexate; prednisone; and TNFi.
That said, patients using prednisone exhibited significantly more weight gain than methotrexate users (and leflunomide users actually exhibited weight loss). It was concluded that prednisone is associated with significantly more weight gain than other treatments for rheumatoid arthritis.
2016: Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy.
Griggs, Miller, Greenberg, et al. compared the safety and efficacy of deflazacort and prednisone in the treatment of Duchenne muscular dystrophy (DMD). Data were assessed from a 52-week double-blind, randomized, placebo controlled trial comprised of 196 boys (ages 5-15) diagnosed with DMD.
Participants were assigned at random to receive either prednisone (0.75 mg/kg/day), deflazacort (0.9-1.2 mg/kg/day), or a placebo for the first 12 weeks. Thereafter, the placebo recipients were assigned to receive an active treatment (prednisone or deflazacort) for the remaining 40 weeks.
Results indicated that weight gain-related adverse effects were more likely to be moderate or severe among prednisone users than deflazacort users. Researchers mentioned that higher rates of weight gain among prednisone users (in comparison to deflazacort users) is consistent with previous data.
After 12 weeks of treatment, there were significant increases in both body weight and BMI among prednisone users – yet there were no such increases in among placebo and deflazacort recipients. Furthermore, after 52 weeks of treatment, prednisone users exhibited significantly greater increases in body weight and BMI than deflazacort users.
There was a trend towards a greater number of participants discontinuing prednisone due to weight gain, however, this was not statistically significant. Overall, this study suggests that prednisone treatment is more likely to cause weight gain than deflazacort among boys with DMD – regardless of whether used for a short-term (12 weeks) or long-term (52 weeks).
2015: Effects of short-term oral corticosteroid intake on dietary intake, body weight and body composition in adults with asthma – a randomized controlled trial.
Berthon, Gibson, McElduff, et al. analyzed the effect of short-term oral corticosteroid treatment on: food intake, body weight, and body composition – among adults with asthma. A randomized controlled trial was organized in which 55 adults with asthma were given a 10-day course of oral prednisone (50 mg per day) or a placebo for the management of asthmatic symptoms.
In the trial, researchers measured: leptin levels, appetite, dietary intake, body weight, and body composition. Dual-energy X-ray absorptiometry (DEXA) and bioelectrical impedance analysis measured body weight and composition; a visual analogue scale (VAS) measured appetite; and food records measured dietary intake. Blood samples were collected to evaluate concentrations of leptin and eosinophils.
Results of the study indicate that blood eosinophils significantly decreased with prednisone treatment (compared to the placebo), whereas leptin levels remained unchanged. Additionally, there were no differences in caloric intake, body fat, or body composition – among prednisone recipients compared to the placebo users.
This study indicates that short-term prednisone treatment is unlikely to significantly alter appetite, diet, body weight, or body composition – in adults with asthma. That said, because this study utilized a small sample size, some may question the reliability of results.
2015: Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study.
Bello, Gordish-Dressman, Morgenroth, et al. conducted an observational study assessing the side effects of glucocorticoid medications in the management of Duchenne muscular dystrophy (DMD). A total of 340 persons with DMD were recruited to participate in the study and side effects of prednisone, prednisolone, and deflazacort were documented over a long-term.
Results indicated that patients treated for over a year while walking (252/340) showed a 3-year delay in loss of independent ambulation. The average dose of prednisone administered during this study was 0.56 mg/kg/day – whereas the average dose of deflazacort administered was 0.75 mg/kg/day.
Prevalence of side effects was determined based upon data gathered from 227 participants (86.2%). The most common side effect of all was weight gain (65%), followed by cushingoid appearance (55%), growth delay (37%), and behavior changes (37%). Moreover, researchers noted that side effect frequencies may have been underestimated (based on the fact that side effects were only recorded from the most recent 3 glucocorticoid regimens of patients before baseline).
There were no significant differences in the incidence of weight gain between prednisone and deflazacort treatments. However, researchers documented that low-dose intermittent regimens of prednisone caused lower incidence of side effects – particularly weight gain (which occurred in only 23% of patients receiving low-dose intermittent treatment).
2014: A systematic review of the effect of oral glucocorticoids on energy intake, appetite, and body weight in humans.
Berthon, MacDonald-Wicks, and Wood conducted a systematic review to determine the effect of oral glucocorticoids (like prednisone) on appetite, food intake, body weight, and body composition in humans. For the review, researchers extracted data from peer-reviewed studies that were published in various databases (Medline, CINAHL, EMBASE, Cochrane) between 1973 and 2012.
To be included in the review, studies needed to document the effect of oral glucocorticoids on appetite, energy intake, body weight, or body composition – in adults. A total of 21 studies met inclusion criteria for the review: 6 measuring energy intake; 19 measuring body weight; 3 measuring energy expenditure; 6 measuring body composition; and 3 measuring appetite.
Data from the included studies indicate that short-term oral glucocorticoid therapy can cause slight increases in energy intake, but this does not induce significant increases in body weight – possibly due to simultaneous increases in energy expenditure. However, data also indicate that long-term glucocorticoid administration can cause clinically significant weight gain.
Authors of the review noted that there was interindividual variation in responses to glucocorticoids due to metabolism and physical activity levels. Furthermore, authors reported zero effect of glucocorticoid dosage on: appetite, body weight, body composition, and energy intake. In other words, the dose of glucocorticoids administered had no significant effect in determining whether weight gain would occur.
2013: Increase of body mass index in a tight controlled methotrexate-based strategy with prednisone in early rheumatoid arthritis: side effect of the prednisone or better control of disease activity?
Jurgens, Jacobs, Geenen et al. sought to determine whether body mass index increases among patients with rheumatoid arthritis undergoing treatment – is a side effect of medications used or due to a reduction in disease activity. The researchers assessed data from a study involving 236 participants who had been formally diagnosed with rheumatoid arthritis. Participants had no history of disease-modifying anti-rheumatic drugs (DMARD) use and exhibited an average disease duration of ~1 year.
In the study, participants were assigned at random to receive methotrexate with adjunct: prednisone (10 mg/day) or a placebo – over a 2-year span. It was noted that methotrexate dosage was flexible and adjusted among patients based on responses. Dosages of methotrexate were increased from 5 mg per week to either 30 mg per week or a maximum tolerable dose.
If no symptomatic relief was derived from methotrexate, a different DMARD (adalimumab) was administered. Prior to the study, as well as at various checkpoints throughout the study, researchers collected the body mass index (height and weight) of each participant. Of the 236 original participants, only 224 generated relevant data for evaluation.
Results indicated that weight gain was substantially higher in persons receiving methotrexate plus prednisone (10 mg/day) than in persons receiving methotrexate plus placebo. However, the methotrexate plus prednisone group also exhibited lower DAS28 scores, indicative of reduced disease activity.
Lower DAS28 scores were strongly associated with higher BMIs – regardless of the specific DMARD(s) administered. This finding considered, researchers implied that prednisone (10 mg/day) added to methotrexate did not cause weight gain as a side effect. Instead, it was suggested that greater weight gain among prednisone recipients was attributable to greater reduction in disease activity.
Nevertheless, researchers report several limitations associated with their study, including: the inability to discern whether BMI increases are due to fat or lean mass gain; the lack of information regarding fat distribution; and the difficulty in determining whether prednisone might cause weight gain (irrespective of reducing disease activity). Considering these limitations, this study cannot rule out weight gain as a potential side effect of prednisone.
2011: Glucocorticoid Therapy and Adrenal Suppression.
Chrousos, Pavlaki, and Magiakou published a book that reflected upon the adverse effects of glucocorticoids like prednisone. In the book, researchers outlined the most common adverse effects associated with glucocorticoids – two of which were weight gain and appetite enhancement.
Authors stated that weight gain and appetite enhancement from glucocorticoid treatment were “essentially unavoidable” and begin “early in therapy.” In one portion of the book, authors cited a recent review in which the effect of low-dose glucocorticoids for the management of rheumatoid arthritis were analyzed.
The review concluded that low-dose glucocorticoids cause many adverse effects, one of which is weight gain. More specifically, evidence from this review indicated that 5-10 mg/day of prednisolone (or equivalent) for 2+ years led to an average increase in body weight of 4% to 8% (from baseline).
Additionally, authors discussed the results of a large-scale survey study with over 2,000 long-term, low-dose prednisone recipients (~16 mg/day) – stating that weight gain was reported by 70% of users, making it the most common side effect. (This survey study by Curtis et al. from 2006 was already discussed below; continue reading for more information).
Moreover, an observational study was also mentioned by authors in which 779 patients with rheumatoid arthritis received glucocorticoid treatment and exhibited significant weight gain from dosages at 5 mg (or more) per day. In brief, all studies assessing the adverse effects of corticosteroids (like prednisone) reported weight gain as a side effect.
2008: Effects of Glucocorticoids on Weight Change During the Treatment of Wegener’s Granulomatosis.
Wung, Anderson, Fontaine, et al. evaluated data from a trial in which 157 patients received glucocorticoids (e.g. prednisone) for the treatment of the inflammatory disease Wegener’s Granulomatosis. Researchers recorded the body weights of trial participants at baseline – as well as after 1 year.
Patients were divided into 3 subgroups: multiple flares (average dose 7.9 grams); single flare (average dose 6 grams); and remission (average dose 3.9 grams). Average weight gain among these subgroups over the span of 1 year was: 5.73 lbs. (multiple flare group); 9.03 lbs. (single flare group); and 12.78 lbs. (remission group).
Among all glucocorticoid recipients in the study, average weight gain after 1 year was 8.59 lbs. A total of 38 patients gained and maintained at least 22 lbs. within the year of treatment – with an average increase of 24.69 lbs. Of the 78 patients in the remission group, the average weight gain after 1 year did not decline after 2 years – despite discontinuation of glucocorticoids.
Overall, this research supports the idea that prednisone treatment for 1 year causes an average weight gain ranging from 5.73 lbs. to 12.78 lbs. among patients with Wegener’s Granulomatosis. Interestingly, patients using the lowest glucocorticoid doses and with the best disease control seem to gain the most weight.
Considering that a symptom of Wegener’s Granulomatosis is weight loss, it’s likely that successfully treating the condition with prednisone may lead to weight gain via disease remission – rather than as a side effect of prednisone. Nevertheless, because all treatment groups gained weight (regardless of disease control), some weight gain is likely a side effect of prednisone.
2006: Population-based assessment of adverse events associated with long-term glucocorticoid use.
Curtis, Westfall, Allison, et al. examined survey data collected from adults who had received low-dose glucocorticoids for at least 60 days to determine incidence of adverse effects. For the study, researchers identified 6,517 glucocorticoid users and mailed them a survey questioning adverse effects during treatment.
Of the 6,517 survey recipients, a total of 2,446 returned completed surveys. The demographics of prednisone users based on survey completion was as follows: 71% women, 29% men, 79% Caucasian, 13% African American, ~53 years of age, with ~7 comorbid medical conditions. The average prednisone-equivalent dosage received during treatment was 16 mg per day.
Survey results indicated that over 90% of glucocorticoid users experienced at least 1 adverse effect during treatment – and 55% of these individuals considered the side effect “very bothersome.” The most common self-reported adverse effect reported by 70% of survey responders was weight gain.
Researchers discovered that weight gain and other adverse effects were strongly dose-dependent and time-dependent. Higher dosages and longer-term corticosteroid use resulted in more significant weight gain – than lower dosages (7.5 mg per day or less) and shorter-term corticosteroid use. This study supports the idea that medications like prednisone cause weight gain in a significant number of users – a majority of whom consider it “very bothersome.”
2006: Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data.
Da Silva, Jacobs, Kirwan, et al. published a paper discussing the safety of low-dose glucocorticoids in the treatment of rheumatoid arthritis. In the paper, it was noted that one of the most common effects of excessive glucocorticoid concentrations is redistribution of body fat.
This body fat redistribution is understood to occur regardless of whether the excess glucocorticoids are endogenous (produced by the body) or exogenous (synthetic). Long-term glucocorticoid treatment was associated with the accumulation of centripetal fat (i.e. fat in the abdominal region or midsection) – regardless of whether the dose is high or low.
Researchers speculate that the accumulation of fat from glucocorticoid treatment may be caused by hyperinsulinemia; hormone fluctuations; shifts in cytokine concentrations; sex hormone suppression; increased calorie intake; and muscle loss. The data from this review indicate that low-dose prednisone over 2 years led to an average body weight gain of 4% to 8% (from baseline).
In placebo-controlled trials, weight gain exhibited by low-dose prednisone recipients was significantly greater than weight gain exhibited by placebo recipients. Evidence presented by Da Silva et al. supports the idea that glucocorticoids like prednisone can cause significant weight gain – even at low doses.
2002: Effect of steroids on energy expenditure and substrate oxidation in women with Crohn’s disease.
Al-Jaouni, Schneider, Piche, et al. conducted a study to assess the effect of prednisone (and budesonide) on energy expenditure and substrate oxidation among patients with Chron’s disease. A total of 29 women with Chron’s disease plus 10 healthy controls were recruited for participation and assigned to receive: prednisone (0.75 to 1 mg/kg/day); budesonide (9 mg/day); or no medication.
Researchers measured resting energy expenditure and substrate oxidation of all participants via indirect calorimetry. Results indicated that, when in a fasted state, resting energy expenditure was higher in patients without steroids than in the healthy controls. Patients receiving prednisone exhibited significantly lower lipid oxidation compared to patients receiving budesonide and healthy controls.
After consumption of a meal, lipid oxidation remained significantly lower among prednisone recipients compared to: budesonide recipients, patients who didn’t receive steroids, and healthy controls. Furthermore, measures indicated that protein oxidation was significantly elevated among prednisone recipients than other participants.
It was concluded that, among women with Chron’s disease, prednisone reduces lipid oxidation and increases protein oxidation. Because changes in lipid and protein oxidation were not observed with budesonide, it was hypothesized that these might be mechanisms by which prednisone induces weight gain.
Overall, the results of this study support the idea that prednisone causes weight gain. Researchers suspect that consuming a high-protein, low-fat diet could help prevent or reduce prednisone-induced weight gain.
1995: Prednisone as adjunctive therapy in the management of pulmonary tuberculosis. Report of 12 cases and review of the literature.
Muthuswamy, Hu, Carasso, et al. conducted a retrospective chart review for 5 years (1988 to 1993) to examine the effect of adjunct prednisone in 12 patients diagnosed with pulmonary tuberculosis. Prior to initiation of prednisone treatment, it was noted that all of these patients exhibited abnormally high body temperatures and substantial weight loss.
All 12 patients received prednisone (20 to 60 mg) until body temperature normalized and clinical improvement occurred. Researchers documented body temperature reductions in all 12 patients within 24 hours of adjunct prednisone treatment. The average length of oral prednisone therapy needed in these 12 patients was ~20.1 days.
Results indicated that prednisone treatment: stimulated appetite and increased body weight from 53.6 kg (118.16 lbs.) to 58.1 kg (128.08 lbs.). This indicates that prednisone treatment for an average of 20 days led to an average weight gain of 9.92 lbs. Though some of the weight gain was probably due to a reduction in disease activity – it’s likely that a percentage of the weight gain was directly attributable to prednisone.
1981: A prospective study of methylprednisolone and prednisone as immunosuppressive agents in clinical renal transplantation.
Burleson, Marbarger, Jermanovich, et al. conducted a double blind crossover trial with 65 patients receiving methylprednisolone and prednisone as immunosuppressant agents following renal transplantation (to prevent organ rejection). The aim of the trial was to examine effects of each corticosteroid in terms of graft survival and adverse reactions, one of which was weight gain.
After 1 year of treatment, there were zero significant differences in graft survival among the patients. The average weight gain associated with each intervention over a 1-year duration was 8.37 lbs. (prednisone) and 5.07 lbs. (methylprednisolone) – not significantly different.
However, researchers mentioned that when methylprednisolone was used in the late post-transplant period, patients had substantially less weight gain (2.09 lbs.) than if prednisone was used during the late post-transplant period (7.71 lbs.). Despite the fact that most patients (65%) didn’t prefer one drug over the other, patients with a preference preferred methylprednisolone – possibly due to lower average weight gain.
That said, because prednisone was associated with a significantly lower risk of sepsis, prednisone is the top choice as an immunosuppressive steroid during renal transplantation. Though this was a relatively small-scale study, it supports the idea that prednisone can cause weight gain of ~8.37 lbs. when administered for a long-term following renal transplantation.
Based on the research does Prednisone cause weight gain?
Yes – particularly when administered for a long-term.
Nearly all studies highlighted above indicate that prednisone treatment causes weight gain. Patel et al. (2018) noted that weight gain was the most frequently reported side effect of prednisone, accounting for 8.2% of all side effect reports – and increased appetite was the third-most frequently reported side effect (7.5% of reports). Furthermore, Savas et al. (2017) suggested that 10.5% of obese individuals may have experienced significant weight gain as a result of using prednisone (or other corticosteroids) for a long-term.
Evidence presented by Aljebab et al. (2017) in a systematic review indicated that 21.1% of pediatrics (up to 18 years of age) using prednisone for a long-term will experience weight gain. Additionally, Baker et al. (2016) reported that prednisone usage in patients with rheumatoid arthritis causes significantly more weight gain than usage of methotrexate and leflunomide (this was based on a study encompassing 32,859 patients).
Griggs et al. (2016) documented that prednisone caused significantly more weight gain among boys with Duchenne muscular dystrophy following 12 weeks and 52 weeks of treatment –compared to a placebo and deflazacort. Earlier work by Bello et al. (2015) documented weight gain in 65% of patients receiving prednisone for the treatment of Duchenne muscular dystrophy.
A systematic review by Berthon et al. (2014) reported no weight gain with short-term corticosteroid use, but clinically significant weight gain with long-term corticosteroid use. In 157 patients with Wegener’s Granulomatosis, Wung et al. (2008) reported weight gain between 5.73 lbs. and 12.78 lbs. after 1 year – regardless of disease control, indicating that weight gain is a side effect of prednisone treatment.
A large-scale survey by Curtis et al. (2006) comprised of 2,446 individuals (who underwent corticosteroid treatment for at least 60 days) reported weight gain in 70% of the sample, suggesting that it is the most common side effect. Work by Da Silva et al. (2006) further suggested that corticosteroids can cause weight gain of 4% to 8% over a long-term (2+ years) – even at low doses.
Studies by Al-Jaouni et al. (2002), Muthuswamy et al. (1995), and Burleson et al. (1981) also indicate that prednisone causes weight gain. Al-Jaouni et al. (2002) reported significant weight gain as a side effect (along with unfavorable metabolic effects), Muthuswamy et al. (1995) reported weight gain of 9.92 lbs. in 20 days with prednisone treatment (among patients with pulmonary tuberculosis), and Burleson et al. (1981) reported weight gain of 8.37 lbs. (among patients using prednisone for 1 year following renal transplant).
Of all studies investigated, just 2 suggest that prednisone might not cause weight gain as a side effect. Berthon et al. (2015) reported that a 10-day course of prednisone (50 mg) in 55 healthy adults with asthma caused no changes in body weight, calorie intake, or body composition.
Moreover, a study by Jurgens et al. (2013) implied that prednisone may not cause weight gain as a side effect. Instead, Jurgens et al. suggested that weight gain observed during prednisone treatment is probably due to remission of disease activity – based on the finding that decreases in symptom severity of rheumatoid arthritis correlated with increases in BMI among participants.
That said, in the Berthon et al. study, the reason significant weight gain probably didn’t occur in this group is due to the extremely brief treatment period (just 10 days). Additionally, in the Jurgens et al. study, concurrent use of methotrexate was a notable confound – and researchers were unable to fully dismiss the possibility that a percentage of the weight gain observed was a side effect of prednisone.
In summary, it seems as though significant weight gain is unlikely to occur when prednisone is administered for an extremely brief duration. However, clinically relevant weight gain is likely to occur when prednisone is administered for a long-term – regardless of its dose.
Variables that influence Prednisone-mediated weight gain
There are a host of variables that might impact one’s odds of gaining weight while using prednisone and the significance of weight gain (among persons who experience this side effect). Variables that are likely most influential in determining whether weight gain is likely to occur while using prednisone include: length of treatment and preexisting medical conditions (and the efficacy of prednisone in reducing disease activity).
Other variables such as: prednisone dosage (relative to body size); administration frequency; concurrent substance use; prior substance use; baseline body weight and composition; lifestyle; and genetics – could also influence odds of experiencing weight gain as a side effect. It is the cumulative influence of these variables that likely account for differences in weight gain among prednisone users.
Length of prednisone treatment
Perhaps the most influential variable in determining whether weight gain will occur while taking prednisone is length of treatment. Although some studies suggest that prednisone might not cause weight gain if administered over a short-term, data are consistent in suggesting that long-term prednisone usage induces clinically relevant weight gain in a moderate percentage of users.
Interestingly, length of treatment matters more than prednisone dosage as an influencer of weight gain. Low-dose prednisone use is associated with just as much weight gain over a long-term as high doses. (In some cases, low dose prednisone is associated with even more weight gain over a long-term compared to high dose prednisone).
Researchers believe that cumulative physiologic exposure to prednisone over an extended duration causes weight gain, irrespective of the prednisone dose. For this reason, long-term prednisone users should be considered at increased risk of clinically relevant weight gain – when compared to short-term prednisone users.
Medical conditions & efficacy of prednisone
Any preexisting medical conditions with which you’ve been diagnosed could determine the amount of weight that’s gained while taking prednisone. In the event that you have a medical condition that causes weight loss and/or leads to development of an underweight body mass index (BMI), there’s a chance that weight gain on prednisone will be contingent upon how well the disease is managed.
If prednisone proves effective for the treatment of a medical condition caused weight loss, it’s likely that you’ll experience weight gain due to the attenuation of disease activity. In other words, if rheumatoid arthritis caused you to lose 20 lbs., and prednisone treatment leads to remission of rheumatoid arthritis – then you may regain the 20 lbs. that you lost while exhibiting high disease activity.
If prednisone is partially effective in managing your medical condition that caused weight loss, you’ll likely experience some weight re-gain. For example, if an autoimmune condition causes you to lose 20 lbs., and prednisone reduces disease activity by 50%, you might gain back half of the weight that was lost (e.g. 10 lbs.).
Prednisone dosage (Low vs. High)
Although prednisone can cause weight gain at both high and low doses, weight gain may occur earlier in treatment among high dose users – than low dose users. Research by Ellero-Simatos et al. (2012) indicates that prednisone dose-dependently alters amino acid metabolism – such that higher doses modulate amino acid metabolism to a greater extent than lower doses.
Moreover, because higher doses of prednisone exert stronger physiologic effects than lower doses – it’s likely that higher doses would modulate oxidation (of fat and protein) and hormones to a greater extent than lower doses. This might result in high-dose prednisone users exhibiting lower testosterone, greater fat accumulation, and more substantial muscle loss –than lower dose users.
Furthermore, side effects tend to be more prevalent and/or of greater severities at high doses compared to low doses. If side effects that directly or indirectly cause weight gain (e.g. increased appetite, hormone changes, cognitive dysfunction, mood swings, etc.) are more numerous and/or harsher at high doses – this might yield greater weight gain with high-dose prednisone administration (than low-dose administration).
Frequency of Prednisone administration
Some individuals will require prednisone to be administered on a daily basis for adequate disease control, whereas others might only need to use prednisone every other day, several times per week, or less frequently. The greater the frequency at which prednisone is administered, the more likely a user will end up gaining weight.
This is because if you’re administering prednisone frequently (e.g. daily), you’re: enduring a greater number of exposures to prednisone; the physiologic changes induced by prednisone are maintained and/or amplified; and your body is unable to revert back to homeostasis. On the other hand, the lesser the frequency at which prednisone is administered, the lower the likelihood of weight gain.
This is because if you’re using prednisone infrequently (e.g. once a week), you’re: enduring fewer exposures; preexisting physiologic changes induced by prednisone are not amplified; and certain physiologic processes may revert (at least partially) back to homeostasis. Additionally, a lower percentage of prednisone will be in your system (to modulate your physiology) with lower frequency dosing – thereby minimizing odds and/or degree of weight gain.
Concurrent substance use
If you’re using substances along with prednisone, it’s necessary to realize that these agents could increase or decrease risk of experiencing prednisone-mediated weight gain. Certain agents that you’re using could: augment OR counteract the physiologic mechanisms by which prednisone causes weight gain.
If the concurrent substances that you’re using augment the mechanisms by which prednisone causes weight gain, the amount of weight that you gain during treatment may be more substantial than if you were using prednisone as a standalone substance. For example, if you’re using prednisone with another medication that stimulates appetite and reduces testosterone – weight gain may be severe and impossible to avoid.
If the concurrent substances that you’re using counteract the mechanisms by which prednisone causes weight gain, the amount of weight that you gain during treatment may be less substantial than if you were using prednisone as a standalone agent. For example, if you’re using prednisone with a medication that increases testosterone, speeds up metabolism, and/or suppresses appetite – then you may not experience weight change during treatment.
Baseline body weight and composition
It’s possible that baseline body weight and composition of a prednisone user could influence the amount of weight gain that occurs while using prednisone. Someone with a high body weight (relative to prednisone dose) at baseline might be at increased risk of weight gain with prednisone than someone with a low body weight (relative to prednisone dose) at baseline.
Another possibility is that someone with a high body fat percentage and/or low percentage of lean mass – may be prone to greater weight gain during prednisone treatment than someone with a low body fat percentage and/or high percentage of lean mass. Increased risk of weight gain among overweight and/or obese prednisone users could be due to synergistic interactions between prednisone and preexisting obesity-related: hormone imbalances; dysbiosis; inflammation; etc.
Because this hasn’t been extensively researched, it remains unclear as to whether persons with high weights and/or BMIs at baseline are prone to greater weight gain during prednisone treatment than those with normal or low weights and/or BMIs. Nevertheless, baseline weight and body composition of the prednisone user are variables worth considering as potential determinants of weight gain during treatment.
Lifestyle & genetics
The lifestyle and genetics of prednisone users might also determine whether they’ll experience significant weight gain during treatment. Someone who makes a consistent effort to live as healthy as possible while using prednisone may not experience nearly as much weight as a person who makes zero effort to live a healthy lifestyle.
An individual who regularly exercises and monitors calorie intake already has healthy lifestyle habits in place that should help limit or counteract prednisone-mediated weight gain. On the other hand, a person who never exercises or monitors calorie intake might succumb to food cravings on prednisone and end up consuming significantly more calories than they did before using prednisone – leading to weight gain.
In addition to lifestyle habits, a prednisone user’s gene expression might influence weight gain during treatment. Though the relationship between gene expression and corticosteroid-induced weight gain hasn’t been researched, it’s possible that expressing certain genes could protect against and/or minimize the significance of prednisone-induced weight gain – compared to expressing other genes.
Recent substance use & discontinuation
If you recently used and discontinued a substance just prior to initiating treatment with prednisone, and that substance caused significant weight change – this might impact whether you notice weight change with prednisone. In the event that you discontinued a medication that caused weight gain just prior to using prednisone, you might not experience weight gain after initiation of prednisone.
As an example, let’s say you formerly used the medication methylprednisolone (which acts similar to prednisone) – and initiated prednisone treatment immediately after methylprednisolone cessation. Because your body hadn’t lost the weight that was gained with methylprednisolone, it may simply maintain weight (or gain a small amount) after prednisone initiation; causing you to experience less weight gain following prednisone initiation (than if you had no recent history of methylprednisolone use).
As another example, someone might’ve used a medication that caused substantially more weight gain than prednisone. If this medication is discontinued just prior to prednisone initiation, a user might actually experience some weight loss during prednisone treatment – mostly due to the fact that the body is shedding pounds that were packed on from the former medication (not because the prednisone is causing weight loss).
Lastly, if you used a medication prior to prednisone that caused significant weight loss, then you might notice significant weight gain while taking prednisone. In this case, a significant percentage of weight gain that’s noticed while using prednisone could be due to body weight rebound after discontinuing the medication that was causing weight loss and/or aiding in the maintenance of a lower body weight.
Potential ways to minimize Prednisone-induced weight gain
Included below are some strategies that may prove effective in minimizing weight gain and/or deleterious body composition changes while using prednisone. Understand that these strategies haven’t been extensively researched and may be ineffective for some prednisone users. Before implementing any of the strategies listed below – speak with a medical doctor to verify that they’re safe (in accordance with your present medical status).
- High protein, low fat diet: A study by Al-Jaouni et al. (2002) discovered that prednisone increases protein catabolism and decreases fat oxidation. Essentially, this means that the body is burning more protein and less fat –leading to fat gain with concurrent muscle loss. To prevent unfavorable changes in body composition and weight gain while using prednisone, researchers suggest that it may be best to consume a high protein/low fat diet.
- Limit calories: Another strategy for preventing weight gain on prednisone involves limiting calorie intake and consuming either “maintenance calories” or a “hypocaloric diet.” Obviously calories should not be restricted if you’re underweight (due to a medical condition) and need to gain weight. However, if you’re already at a high body weight and need to prevent weight gain on prednisone, consuming fewer calories than your body is expending should help counteract some of the weight gain during treatment.
- Exercise regularly: Regular exercise can help preserve lean mass and maximize your metabolic rate during prednisone treatment. Resistance training coupled a high protein diet should help prevent and/or reduce the likelihood of prednisone-induced muscle loss (and unfavorable changes in body composition). Additionally, regular aerobic exercise should help the body burn extra calories, maintain a high metabolic rate, and/or reduce appetite. If you’re gaining weight on prednisone, try counteracting the weight gain with exercise.
- Manage side effects: As was discussed, some weight gain that occurs while using prednisone could be attributable to side effects like: increased appetite, bloating, and/or constipation. If your weight gain on prednisone is due to an abnormally high appetite, bloating, and/or constipation – discuss these side effects with a medical doctor and ask about potential management strategies. If your doctor can recommend an effective treatment for the specific prednisone side effect(s) culpable for a percentage of your weight gain – then you should be able to reduce your weight. For example, if your appetite surges as a side effect of prednisone and this leads to overeating, your doctor may be able to recommend an appetite suppressant to counteract this reaction.
- Limit duration or frequency treatment: If your aim is to minimize and/or prevent weight gain, it is recommended to limit the duration and/or frequency of prednisone administration (with respect to your medical status). Nearly all research of prednisone indicates that regular long-term administration is associated with significant weight gain (even at low doses), whereas short-term and/or infrequent prednisone administration (even at high doses) is less likely to cause weight gain. Work with your doctor to establish the minimal effective dosing frequency and treatment length for your condition.
- Use a low dose (if possible): Although low doses of prednisone can cause weight gain (especially if administered over a long-term), fewer metabolic changes result from low doses – particularly in the early stages of treatment. Additionally, lower doses of prednisone exert less potent effects upon physiology than high doses. This means that weight gain resulting from low-dose prednisone administration may be less substantial than weight gain from high-dose prednisone administration. Assuming all user-specific factors are equal (e.g. body size, disease activity, etc.), it’s reasonable to speculate that weight gain and unfavorable body composition changes will be more significant with higher doses (than low doses). For this reason, it’s recommended to work with your doctor to find the minimal effective dose of prednisone needed to manage your medical condition.
- Eliminate substances: If you’re using concurrent substances with prednisone (e.g. medications, supplements, etc.), some of the weight gain that you experience could be attributable to those other substances. Concurrent substance use might: induce similar side effects as prednisone that lead to weight gain; augment physiologic changes induced by prednisone to promote weight gain; and/or cause weight gain irrespective of prednisone. This considered, some individuals may find that discontinuing medically unnecessary substances helps reduce weight gain on prednisone.
- Add-on substances: If you require prednisone for the management of a medical condition yet none of the aforementioned strategies seem to help counteract the weight gain side effect – then you may want to ask your doctor about utilizing adjunct substances (e.g. medications) to either: prevent further weight gain OR promote weight loss. A medical doctor may be able to recommend a medication that can be safely used with prednisone to combat its side effects (e.g. appetite increase) and/or physiologic effects (e.g. low testosterone) that lead to weight gain.
Note: If you’ve employed the above strategies in attempt to counteract or mitigate prednisone-induced weight gain, but none seem to be helping, it is recommended that you discuss your weight gain with a medical doctor. A medical doctor may recommend undergoing prednisone withdrawal and switching to a different medication (to manage your symptoms) that’s associated with lower rates of weight gain.
Have you experienced weight gain on prednisone?
In the event that you have a history of using prednisone, leave a comment mentioning whether you experienced weight gain (as a side effect) while using it. Assuming you tracked your body weight while using prednisone, approximately how much weight did the medication cause you to gain?
In your experience, was the weight gain considered favorable, such as weight regain from autoimmune-induced weight loss? Or was the weight gain considered unfavorable – and associated with deleterious body composition changes (such as increased fat around the midsection and muscle loss)?
From your perspective, what do you believe were the underlying reasons for your weight gain on prednisone? Possible reasons might include: overeating (due to increased appetite, food cravings, mood swings, etc.); metabolic and hormone changes (e.g. high insulin, lower testosterone, etc.); side effects (e.g. bloating and constipation); or reversal of disease activity (e.g. remission of rheumatoid arthritis).
To help others get a better understanding of your experience using prednisone, provide additional details in your comment such as: how long you used prednisone; your prednisone dosage; the medical condition for which you were using prednisone; and whether you used other substances (e.g. medications) with prednisone.
If you used other medications with prednisone, have you investigated whether these agents could’ve been culpable for some of your weight gain? If you’ve gained a significant amount of weight on prednisone, have you tested any of the strategies listed above to help reverse it? (If so, were any of these strategies effective?)
Overall, it seems as though some weight gain may be inevitable for long-term prednisone users (regardless of the dose). In many cases, weight gain on prednisone is considered healthy because it is attributable to a reversal of disease activity (and disease-associated weight loss). Nevertheless, if you’ve gained an unhealthy amount of weight on prednisone and are struggling to manage it – consult a medical doctor and ask whether it would be possible to switch to a different medication that’s less likely to cause weight gain (for the treatment of your specific condition).