Keywords
weight cycling - yo-yo dieting - women - reproductive outcome - diabetes
Weight cycling or “yo-yo dieting” refers to intentional weight loss followed by unintentional
weight regain. Weight cycles are measured as a change in weight or percent body weight
over an interval of time. The magnitude of a weight cycle varies from the loss and
regain of ≥ 2.25 to 10 kg or ≥ 5 to 10% of body weight over months to years in most
studies.[1] While there is no standard definition of a weight cycle, the thresholds cited in
studies exceed typical weight fluctuations and exceed changes in percent body weight
that are associated with changes in obesity-related outcomes.[2]
[3]
Dieting is a common experience among reproductive-age women, even while trying to
conceive. In the 2013–2016 National Health and Nutrition Examination Survey (NHANES),
almost 60% of U.S. reproductive-age women reported trying to lose weight in past year,
including more than 70% of women with obesity and 35% of women with normal weight.[4] The most commonly reported approaches were eating less (62%) and exercising more
(62%). In a prospective cohort of more than 600 U.S. women who were trying to conceive,
44% reported trying to lose weight in the past year.[5] Most reported a plan to control food intake (79%), while some resorted to extreme
exercising (11%) or shake diets (9%). Another study found that women trying to conceive
were more likely to engage in unhealthy weight loss practices, including taking diet
pills, supplements, and herbs, compared with women who were not trying to conceive.[6]
While most women can achieve short-term weight loss, few women will maintain long-term
weight loss, which has been defined as losing 10% of body weight and maintaining it
for at least 1 year.[7] Only approximately 20% of overweight men and women maintain long-term weight loss.
The low prevalence of long-term weight loss appears consistent in observational trials
that collect self-reported weight change history and in clinical trials that collect
weight measurements in clinics. While few studies of long-term weight maintenance
are limited to women, analysis that compare gender have found that women have more
success at long-term weight loss than men (19.2 vs. 15.6%, odds ratio [OR]: 1.2; 95%
confidence interval [CI]: 1.1–1.3).[8] Given the high prevalence of dieting and weight regain, it is estimated that 20
to 55% of women weight cycle and that at least 20% of women experience frequent weight
cycles, occurring almost yearly.[9]
Maintenance of long-term weight loss is a challenge due to homeostatic regulation
of body weight. Weight is tightly regulated by hormones produced by the gut and adipocytes
that act through the nervous system to alter behavior and metabolism.[10] While most gut peptides increase satiety, ghrelin is the only gut peptide that increases
hunger. Ghrelin is secreted by the gastric fundus and body when the stomach is empty.
Ghrelin secretion stimulates the orexigenic neuron system, the weight gain pathway
in the central nervous system (CNS), which is mediated by neuropeptide Y (NPY)/agouti-related
peptide (AgRP) neurons. As the stomach is stretched by food, ghrelin secretion is
inhibited and hunger declines. All other gut peptides suppress hunger through short
acting effects on the CNS and vagal afferents to trigger meal termination. Examples
of these gut peptides include cholecystokinin (CCK), which is secreted by the small
intestine, and glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY
(PYY), which are secreted by the small intestine and the colon. Macronutrients, such
as carbohydrates, fats, and proteins, stimulate the secretion of these gut peptides.
Weight loss leads to gut peptide secretion changes that promote hunger and weight
regain to restore the energy deficit. Sumithran et al observed that ghrelin levels
increased and CCK and PYY levels decreased over the first 10 weeks of weight loss
in overweight and obese men and postmenopausal women who lost more than 10% of their
body weight.[11] Ghrelin levels increased between 10 and 62 weeks after weight loss, despite weight
regain, and remained significantly higher than pre–weight loss levels. CCK and PYY
levels also remained significantly lower than pre–weight loss levels. Increased ghrelin
levels also occur among normal-weight women who lose weight.[12]
Weight change alters insulin and leptin levels, which regulate long-term energy storage.
Insulin is secreted by the pancreas and converts glucose to glycogen in muscle and
the liver and also promotes triglyceride storage in adipose tissue.[13] Leptin is produced by adipocytes and promotes lipolysis and inhibits lipogenesis
by reducing adipocyte sensitivity to insulin.[14] Both insulin and leptin circulate in levels that correlate with adiposity. As adiposity
increases, insulin and leptin levels increase. Increased insulin and leptin levels
act centrally to reduce food intake and increase energy expenditure. Both insulin
and leptin inhibit the NPY/AgRP neuron system, or weight gain pathway in the CNS.
Leptin also stimulates the proopiomelanocortin neuron system, or weight loss pathway
in the CNS. Resistance to insulin and leptin appears to contribute to obesity in some
individuals who exhibit high circulating levels of these hormones without the anticipated
weight loss effects. While leptin resistance may be induced by chronically elevated
levels of circulating leptin due to obesity, low levels of leptin appear to persistently
increase appetite and reduce energy expenditure to promote weight gain. Leptin levels
decline by 65% by 10 weeks of weight loss.[11] Sumithran et al found that leptin levels increase between 10 and 62 weeks after
weight loss but remain 35% lower than pre–weight loss levels despite weight regain.
Weight loss also triggers a reduction in energy expenditure which enables metabolism
and physical activity at lower caloric cost. Energy expenditure is expected to decline
with weight loss as less energy is needed to support a lower weight; yet, the observed
reduction in energy expenditure often exceeds the predicted reduction in energy expenditure
after weight loss.[15] Participants in a reality weight loss show called “The Biggest Loser” were found
to have mean resting metabolic rates that were 300 to 500 kcal/day lower than expected
at 6 and 30 weeks after significant weight loss that exceeded 30% of their body weight.
The reduction in resting energy expenditure appeared to persist for up to 6 years
after significant weight loss, even despite weight regain.[16] Nonresting energy expenditure is also reduced after weight loss. Skeletal muscle
efficiency improves by 20% following weight loss, resulting in a reduction in the
caloric demand to perform an activity compared with the caloric demand to perform
the same activity prior to weight loss.[17] As a result, long-term weight loss often requires ≥ 1 hour per day of moderate physical
activity for years after weight loss.[7]
Weight loss leads to prolonged changes in leptin levels, gut peptide secretion, and
energy expenditure that promote hunger and weight regain, supporting the notion that
the low rate of long-term weight loss is driven by physiology more so than a lack
of discipline among dieters. Collectively, these adaptions can promote excess weight
regain and altered body composition in some.[18] In cross-sectional studies, women who are obese and weight cycle had increased subcutaneous
adipose tissue, visceral adipose tissue, and waist circumference compared with women
who are obese and weight stable.[19]
[20] A reanalysis of the Minnesota Starvation Experiment, where 12 healthy men were starved
and refed, provides additional insight into the magnitude and nature of excess weight
gain.[21] Participants gained an excess of 4 kg on average (range: 0–9 kg) with refeeding
and experienced restoration of adipose tissue before lean muscle. Overshooting weight
gain induces changes in blood glucose, insulin, lipids, blood pressure, and sympathetic
tone that favor insulin resistance, dyslipidemia, and hypertension.[22] It has been hypothesized that repetitive overshooting through weight cycling may
cause fluctuations in the risk of metabolic and cardiovascular disease ([Fig. 1]).[9]
Fig. 1 Concept of repeated overshooting. Weight cycling may lead to fluctuations in cardiometabolic
surrogate markers with improved parameters observed with weight loss and worsening
parameters observed with weight gain. Repeated weight cycles may lead to cardiometabolic
disease if the baseline drifts with weight cycling (C). (Reprinted with permission
from Montani et al.[9])
It is debated if weight cycling leads to reproductive, metabolic, and cardiovascular
disorders in women with obesity. This article will review the impact of weight change
on pregnancy and pregnancy outcomes as well as the impact of weight cycling on the
risk of diabetes, hypertension, cardiovascular disease, cancer, and mortality among
women.
Weight Change and Pregnancy
Weight Change and Pregnancy
Over 40% of reproductive-age women in the United States are obese, defined as a body
mass index (BMI) of 30 kg/m2 or greater.[4] Epidemiologic studies have consistently associated obesity with infertility and
a reduction in live birth due to delayed conception and higher rates of miscarriage
and stillbirth. However, randomized controlled trials of preconception weight loss
prior to fertility treatment have not consistently shown increased live birth.[23]
[24]
[25]
Despite a lack of high-quality evidence that supports benefits of weight loss prior
to pregnancy, many women attempt to do so. In a prospective cohort of over 600 women
trying to conceive, 44% of women reported a desire to lose weight in the preceding
12 months.[5] While 12% of women achieved weight loss, 58% experienced weight gain. Though few
studies have considered preconception weight cycling as a variable, we will review
the data regarding preconception and interpregnancy weight change with pregnancy outcomes
and argue that weight cycling should be considered in future studies.
Weight change in the weeks, months, and years that precedes pregnancy appears to influence
the risk of miscarriage. In the preliminary report of a randomized control trial,
the risk of early pregnancy loss was 6.1-fold higher (Relative Risk: 6.1, 95% CI 1.4–25.8,
P = 0.005) in women with obesity and unexplained infertility who underwent a 16-week
intensive lifestyle intervention prior to fertility treatment compared with women
who received a standard lifestyle intervention.[26] Data regarding weight loss maintenance and weight regain were not available in the
abstract. In a prospective cohort, weight loss of ≥ 5% of body weight in the 12 to
18 months preceding a spontaneously conceived pregnancy was not consistently associated
with miscarriage, though the cohort included women with normal, overweight, and obese
BMIs.[5] Weight cycling was not associated with the risk of miscarriage, though the magnitude
and frequency of weight cycling was not reported and the stratified data did not categorize
women with a BMI of ≥30 kg/m2 as a subgroup. Weight gain of ≥5% was associated with an increased risk of early
pregnancy loss (RR: 1.65, 95% CI: 1.09–2.49) compared with the weight stable group,
though the association was no longer significant once the data were stratified by
women with a BMI of 18.5 to 24.9 and a BMI of ≥25 kg/m2. In a different prospective cohort, weight gain of ≥20 lb from the age of 18 years
to the age at conception was associated with a 11% increased risk of miscarriage (95%
CI: 1–23%) and women who lost ≥4 kg between the age of 18 years and the time of conception
had a 20% lower risk of miscarriage (95% CI: −29% to −9%), particularly when women
were overweight at the age of 18 years.[27] Data regarding weight cycling were not provided in the analysis.
Weight gain as an adult is associated with the risk of preeclampsia; on the contrary,
weight cycling was not. In a prospective cohort of U.S. women, weight gain of ≥10 kg
from the age of 18 years to their age at conception was associated with a 5.1-fold
(RR: 5.1, 95% CI: 2.2–12.2) increased risk of preeclampsia compared with women who
maintained their adult weight.[28] A history of weight cycling was associated with a 1.5-fold increased risk of preeclampsia,
though the association was attenuated (adjusted RR: 1.1, 95% CI: 0.6–1.8) after adjusting
for maternal age, race, parity, BMI at the age of 18 years, and weight change since
the age of 18 years. There was no evidence of a linear relation between the number
of intentional weight cycles and increasing risk of preeclampsia (p for linear trend = 0.831), although only 1.9% of the cohort was obese based on BMI
prior to pregnancy. Data regarding weight loss and preeclampsia risk were not available.
Weight change between pregnancies is associated with pregnancy outcomes even though
timing between pregnancies is highly variable. In a prospective cohort of Swedish
women, a BMI increase of ≥3 units over approximately 2 years between pregnancies was
associated with an increased risk of preeclampsia (RR: 1.78, 95% CI: 1.52–2.08); gestational
hypertension (RR: 1.76, 95% CI: 1.39–2.23); gestational diabetes (RR: 2.09, 95% CI:
1.68–2.61); caesarean delivery (RR: 1.32, 95% CI: 1.22–1.44); stillbirth (RR: 1.63,
95% CI: 1.20–2.21); and large-for-gestational-age (LGA) infant (RR: 1.87, 95% CI:
1.72–2.04) compared with women who are weight stable between pregnancies. The increased
risks were observed for women with normal and obese pre-pregnancy BMIs.[29] Several meta-analyses have confirmed the association of modest interpregnancy weight
gain and increased risk of perinatal complications, particularly when normal weight
women gain weight.[30]
[31]
[32] Weight loss between pregnancies was not associated with a protective effect on perinatal
complications, except for a reduction in risk of LGA infant and gestational diabetes
among women who were overweight or obese before their first pregnancy. Weight loss
between pregnancies was associated with increased risks of small-for-gestational-age
infant and preterm birth.[32]
Overall, preconception and interpregnancy weight gain are associated with increased
risks of miscarriage, still birth, preeclampsia, gestational diabetes, and caesarean
delivery; yet, weight loss is not associated with a reduced risk of most perinatal
outcomes and may increase the risk of some. Weight maintenance, or preventing weight
gain, during the preconception period and between pregnancies should be encouraged
to avoid the risks associated with weight gain and loss. Only two studies have analyzed
the association of weight cycling and pregnancy outcomes and both studies were based
on women who were normal weight and overweight, with few women with obesity.[5]
[28] Weight cycling is common, particularly among women with obesity, and should be considered
as a variable in future studies of weight and pregnancy outcomes. Investigators should
consider the timing of pregnancy and fertility treatment relative to the weight cycle—loss,
plateau, and regain.
Weight Cycling and Type 2 Diabetes
Weight Cycling and Type 2 Diabetes
Women who weight cycle appear to have a higher risk of diabetes than men who weight
cycle, though few studies have focused on women.[33] In an analysis of over 3 million participants in the National Health Insurance Service
in South Korea, weight fluctuation was assessed over three weights recorded over a
5-year period and new-onset diabetes was recorded over a 5-year follow-up period.
Weight fluctuation was associated with a higher risk of new-onset diabetes (hazard
radio [HR]: 1.10, 95% CI: 1.07–1.12) after adjusting for baseline BMI. The risk was
highest among participants with a BMI of 25 kg/m2 or more, which is considered obese in Asian populations. The risk was also higher
among women (HR: 1.14, 95% CI: 1.1–1.17) compared with men (HR: 1.08, 95% CI: 1.06–1.10;
p = 0.001). The association of weight cycling and type 2 diabetes risk has also been
observed among U.S. women. In a population-based sample of over 33,000 postmenopausal
women enrolled in the Iowa Women's Health Study, self-reported body weights were recorded
at ages 18, 30, 40, and 50 years and were used to calculate weight change.[34] Weight cycling was associated with a 1.4-fold increased risk of diabetes after adjusting
for age and BMI. Other studies have observed an association of weight cycling and
type 2 diabetes in middle-aged women, but the association is no longer significant
once adjusted for BMI. In a nested cohort of over 2,000 young and middle-aged U.S.
women enrolled in the Nurses' Health Study II, 20% experienced mild self-reported
weight cycling, defined as ≥10 lb weight loss and regain three or more times, and
1.6% experienced severe weight cycling defined as ≥ 20 lb weight loss and regain three
or more times.[35] Weight cycling was associated with higher BMI, but was not associated with risk
for diabetes among mild weight cyclers (OR: 1.1, 95% CI: 0.89–1.37) or severe weight
cyclers (OR: 1.39, 95% CI: 0.9–2.13) after adjusting for BMI. Similarly, self-reported
weight cycling was no longer associated with type 2 diabetes after adjusting for BMI
(HR: 1.2, 95% CI: 0.8–1.5) in a nested cohort of more than 1,000 middle-aged men and
women in the Framingham Heart Study.[36] The association between weight cycling and type 2 diabetes appears to be small,
which may contribute to the inconsistent findings between studies of different size.
Weight Cycling and Cardiovascular Disease
Weight Cycling and Cardiovascular Disease
While weight gain is associated with an increased risk of hypertension in women, weight
cycling does not appear to be an independent risk factor. In over 46,000 young and
middle-aged women enrolled in the Nurses' Health Study II, for every 10 lb of self-reported
weight gain, the risk of hypertension increased by 20% (OR: 1.20, 95% CI: 1.15–1.24).[37] Neither mild weight cycling (OR: 1.15, 95% CI: 1.00–1.33) or severe weight cycling
(OR: 1.13, 95% CI: 0.79–1.61) was associated with hypertension after adjusting for
BMI and weight gain. In a prospective 30-month study of over 150 overweight men and
women who achieved weight loss through an 18-month lifestyle program, blood pressure
decreased with weight loss and returned to baseline levels after one weight cycle
and did not appear to overshoot.[38]
It is unclear if weight cycling is associated with dyslipidemia and cardiovascular
events in women. In a cross-sectional study of over 450 Italian participants with
obesity, of which 340 were women, self-reported weight cycling of varying degrees
was not correlated with cholesterol, high-density lipoprotein (HDL), or triglycerides
in women after controlling for BMI and age.[39] In a different cross-sectional study of over 480 U.S. women undergoing coronary
angiography for suspected ischemia, self-reported ≥3 weight cycles of ≥10 lb was associated
with 7% lower HDL levels in women.[40] Weight cycles that exceeded 50 lb were associated with a 27% lower HDL level after
controlling for BMI and additional confounders. This cohort was followed up prospectively
for a median of 6 years and despite exhibiting lower HDL values, higher BMI, larger
waist circumferences, and higher values for fasting blood sugar, women who weight
cycled experienced less adverse cardiac outcomes, including cardiovascular mortality,
nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure,
as compared with women who were weight stable (21 vs. 29%, respectively, p = 0.03).[41] In the Iowa Women's Health cohort, self-reported weight cycling of ≥10% body weight
between the ages of 18 and 50 years was associated with an increased risk myocardial
infarction (RR: 1.89, 95% CI: 1.42–2.53) after adjusting for BMI and age.[42] Differences in the definition of weight cycling may contribute to the conflicting
observations.
Weight Cycling and Long-Term Risks
Weight Cycling and Long-Term Risks
Weigh cycling has been associated with an increased risk in cancer and mortality,
though the association does not persist when controlled for covariates, such as BMI.
In a case–control study of over 740 U.S. women, self-reported weight cycling, defined
as losing ≥20 lb and gaining ≥10 lb within a year, was associated with an increased
odds of endometrial cancer (OR: 1.72, 95% CI: 1.37–2.15), though adjustment for BMI
attenuated the increased odds (OR: 1.27, 95% CI: 1.00–1.61).[43] In a prospective cohort of over 69,000 U.S. women enrolled in the Cancer Prevention
Study II Nutrition Cohort, women who experienced weight cycles of ≥10 lb did not appear
to have an increased overall risk of cancer, including endometrial cancer, after controlling
for BMI as a continuous variable and other covariates.[44] In over 62,000 women enrolled in the Cancer Prevention Study II Nutrition Cohort,
women who experienced one to four weight cycles had a 7% reduction in the risk of
overall mortality (RR: 0.93, 95% CI: 0.89–98) and an 11% reduction in the risk of
cardiovascular mortality (RR: 0.91, 95% CI: 0.79–1.04) in a multivariate model stratified
by age that adjusted for alcohol consumption, race, smoking status, educational level,
physical activity level, BMI in 1982, weight change from 18 years of age to 1982,
history of high blood pressure, history of diabetes, and total energy intake. No association
was observed between higher numbers of weight cycles, classified as 5 to 9, 10 to
19, and ≥20, and overall and cardiovascular mortality.[45]
Conclusion
While claims that diets make some “fatter” may be valid, the available evidence suggests
that there are few detrimental effects of weight cycling in women ([Table 1]). There appears to be a modest association between weight cycling with both type
2 diabetes mellitus and dyslipidemia, but no association with hypertension, cardiovascular
events, and overall cancer risk. Interestingly, mild weight cycling may be associated
with a decreased risk of overall and cardiovascular mortality. It appears that the
benefits of reduced weight, even for a short amount of time, outweigh the risk of
weight regain and overshooting.
Table 1
Summary of selected studies on weight cycling and associated risk of adverse reproductive
and cardiometabolic health outcomes in women
|
Outcome
|
Decreased risk
|
Not associated
|
Increased risk
|
Notes
|
|
Miscarriage
|
|
[5]
|
|
|
Preeclampsia
|
|
[28]
|
|
|
Type 2 diabetes
|
|
[35]
[36]
|
[33]
[34]
|
Association appears to be small, which may contribute to the inconsistent findings
between larger and smaller studies
|
|
Hypertension
|
|
[37]
[38]
|
|
|
Dyslipidemia
|
|
[39]
|
[40]
|
|
|
Cardiovascular events
|
|
[41]
|
[42]
|
Differences in the definition of weight cycling may contribute to the conflicting
observations
|
|
Cancer
|
|
[44]
|
[43]
|
Largest prospective study does not show an association
|
|
Mortality
|
[45]
|
|
|
Little is known about the effects of weight cycling during the preconception period
and pregnancy outcomes. Available evidence suggests that among obese and infertile
patients, weight loss in this period fails to improve live birth and most perinatal
outcomes and may introduce some risks. Given the high prevalence of obesity, dieting,
and weight cycling among reproductive-age women, more evidence is needed. Future studies
should consider weight cycling as a variable and determine if pregnancy outcomes differ
when conception occurs during periods of weight loss or weight stability.
