The timing of food consumption is recognized as a significant contributor to body weight regulation. Disruption of sleep-wake cycles from a predominantly diurnal (daytime) to a delayed (evening) lifestyle leads to altered circadian rhythms and metabolic dysfunction. An integrated review examines the available evidence evaluating the link between the timing of eating with weight and with metabolic outcomes, as well as possible mechanistic pathways (e.g., gene expression) that could underlie such a relationship.

The Obesity Epidemic and the Importance of Timing

Obesity is formally recognized as an epidemic by the World Health Organization and is related to many serious medical comorbidities, including type 2 diabetes, hypertension, cardiovascular disease, many cancers, musculoskeletal disorders, obstructive sleep apnea, and nonalcoholic fatty liver disease. While behavioral weight loss approaches are effective at aiding individuals in reducing their initial body weight by 5-10%, obesity prevention remains a primary public health goal, along with identifying behavioral strategies to optimize weight loss and maintenance. Of the many factors contributing to the obesity epidemic, the timing of food consumption is recognized as a significant contributor to body weight regulation.

Circadian Rhythms, Eating, and Metabolism

The underlying mechanisms governing the circadian rhythms of fundamental processes such as sleeping and eating are well characterized. The circadian system enables organisms to synchronize behaviors, metabolism, and physiological processes to sleep-wake cycles. The core clock mechanism is based on a feedback loop involving the transcription factors BMAL1, CLOCK, and NPAS and their targets. Circadian rhythms are ordered hierarchically in mammals with the hypothalamic suprachiasmatic nucleus (SCN) controlling a network of central and peripheral clocks. The SCN responds primarily to light and synchronizes behavioral and physiological rhythms via circadian oscillations in extra-SCN brain circuits and peripheral tissues. Macronutrients (i.e., glucose, fatty acids, and amino acids) and nutrient-sensing molecules (e.g., AMPK, SIRT1, mTOR, and CRTC2) entrain central and peripheral clocks, changing the timing and amplitude of gene expression rhythms and metabolic pathways. However, a disruption in the timing of food availability induces another regulator-the “food entrainable oscillator”. Unlike the SCN, peripheral clocks in the liver, other organs, and the gut microbiome respond to the timing of feeding. Rodent studies have demonstrated that eating out of phase promotes obesity, insulin resistance, fat storage, and inflammation, highlighting the need for examination of the impact of the timing of eating on these parameters in humans.

Gene Expression and the Timing of Eating

Transcriptomics or expression profiling is the study of the complete set of RNA transcripts produced by the genome (transcriptome), under specific circumstances or in a specific cell, using high-throughput methods such as microarray analysis or short-read high-throughput sequencing (RNASeq). Comparison of transcriptomes allows for the identification of genes that are differentially expressed in distinct cell populations or in response to different conditions.

Adipose Tissue and Gene Expression

Persons with obesity have an excess amount of white adipose tissue fat, a major site of energy storage that plays a role in the regulation of metabolism through the release of adipokines. Adipose tissue dysregulation contributes to the development of obesity-related co-morbidities. Adipose tissue constitutes an important source of circulating RNAs, which can regulate gene expression. Such adipose tissue gene expression is differentially altered during various dietary weight loss interventions in obese persons and in short- and long-term overfeeding. Adipose tissue gene expression distinguishes metabolically healthy obese persons and associates with insulin sensitivity and plasma lipid and glucose levels in this population. Adipose tissue is a peripheral oscillator capable of modulating central core clock genes. Moreover, clock genes are expressed in both visceral and subcutaneous adipose tissue depots, and are associated with a number of metabolic syndrome parameters in individuals with obesity. Clock genes control some adipokines, and their expression in adipose tissue exhibits diurnal variation in persons with obesity. In addition, ex vivo explants demonstrate the presence of peripheral circadian oscillators in human adipose tissue that can function independently of the central (SCN) circadian mechanism. Adiponectin-related, cortisol metabolism-related and leptin and leptin receptor-related gene expression all show circadian rhythmicity, with different circadian patterns between visceral and subcutaneous white adipose tissue depots. In addition, adipose tissue from persons with obesity shows a robust insulin signaling circadian rhythm.

Read also: Weight Loss Guide Andalusia, AL

Diet and various dietary interventions affect adipose tissue gene expression. In addition, timed or delayed eating impact circadian rhythms. Given these effects, and the fact that adipose tissue shows circadian rhythms in gene expression, timing of eating should affect adipose tissue gene expression. One study in mice examined this question. Hatori et al. investigated mice who received ad lib or time-restricted feeding of a high-fat diet for 8 hours per day and consumed equivalent calories; those on the time-restricted feeding showed improvements in adipose tissue gene expression. One recent human study has also addressed this important issue. Wehrens et al. studied 10 healthy men, providing three isocaloric meals at 5-hour intervals starting at 0.5 hours from awakening (for 4 days) followed by 5.5 hours from awakening (for 6 days), with 37-hour constant routine assessments following each condition. They sampled adipose tissue during the constant routine assessments following the early and late eating schedules. They demonstrated that PER2 mRNA rhythms were delayed by 1 hour in the later eating condition, suggesting a possible mechanism for the glucose delay that was also observed. Much more research on how delayed timed eating affects adipose tissue gene expression in humans is needed, particularly in studies of longer duration.

Blood and Gene Expression

Given the limited accessibility and subject burden involved in obtaining adipose tissue biopsies, alternative tissues are needed. As a result, a number of blood transcriptome studies have been conducted, as the collection of peripheral blood is minimally invasive and easily accessible. Moreover, the peripheral blood transcriptome is remarkably consistent within samples from a single person but differs across persons. Peripheral blood gene expression profiling in persons with obesity has identified distinct biological pathways associated with obesity and body mass index (BMI). Differential peripheral gene expression, including in genes related to metabolism, signaling and cellular function, distinguish persons with and without obesity. In a study of men of normal weight, the expression of two clock genes, PER1 and PER2, was associated with waist circumference, a marker of abdominal fat accumulation, and plasma glucose concentration, respectively; moreover, BMAL1 and CLOCK gene expression were associated with susceptibility to obesity. Similarly, PER1, PER2, BMAL1, and CRY1 gene expression were correlated with visceral fat adiposity in participants with BMIs of 25 kg/m2 or greater.

Transcriptomic studies using peripheral blood show daily variation in a number of clock genes including PER1, PER2, PER3, DEC1, BMAL1 and CLOCK. In addition, gene expression and rhythmicity were affected by desynchrony between sleep and circadian phase (i.e., mistimed sleep), constant routines, and sleep loss, whereby the number and/or amplitude of genes exhibiting circadian rhythmicity is altered. These studies highlight the gene expression interrelationships between circadian rhythmicity and sleep homeostasis in blood.

Because timed or delayed eating impact circadian rhythms, and blood shows circadian rhythms in gene expression, the timing of eating should affect blood gene expression. However, Wehrens et al., as described above, did not find any changes in clock gene expression in peripheral blood. Much more research examining how delayed timed eating affects blood gene expression in humans is needed.

Eating Patterns and Their Impact

While a common assumption is that most people eat breakfast, lunch, and dinner and a couple of snacks as discrete eating episodes, Gill and Panda described the eating habits of a sample of 156 adults, mean age 27.6 years, mean BMI 24.7 kg/m2, quite differently. Using an app that allowed pictures of food consumed and time stamps of these eating events, they showed that the number of caloric eating events varied from 3 to 11 per day, with 25% of intake occurring before noon, and 35% of intake occurring after 1800h. Half of the sample ate over a period of 14.75 hours, and the timing of this eating period frequently shifted on the weekends, suggesting that “social jetlag” (misalignment of biological and social time) was common. Gupta and colleagues similarly described the eating habits of a sample of 93 healthy Indian adults. Their data illustrated an unstructured pattern of eating such that the average number of eating episodes was 8.5 per day. Additionally, and similar to the findings of Gill and Panda, 60% of their sample ate at least 15h per day, with greater than a third of all intake occurring after 1800h. Later eating was not significantly correlated with BMI; no metabolic outcomes were measured, and weight change within a specific time frame was also not assessed between early versus later eaters. Further, a study of 432 older South Asian adults living in Canada (mean age 65 years), characterized participants’ dinner times as early (before 1800h, 19% of the sample), average (1800h-2000h, 44% of the sample) or late (after 2000h, 37% of the sample). The time of dinner was not related to hemoglobin A1c (HbA1c), apolipoprotein, diastolic blood pressure, or higher BMI. More work clearly is needed to characterize “normal” eating behavior in today’s society, how dinnertime relates to time of sleep onset, and the implications of those eating schedules on weight and metabolism.

Despite these null findings in general community samples for those who report eating on a later schedule, circadian misalignment resulting from shift work, has been shown to alter the circadian rhythms of leptin, cortisol, glucose, and insulin in a carefully controlled 10-day laboratory study. Although these findings indicate that disrupting normally-timed sleep-wake cycles either by misalignment or by sleep restriction impacts weight, adiposity, and metabolism, it is unclear whether meal timing independently plays a causal role in metabolic dysregulation when sleep-wake cycles are held constant among persons with obesity.

Night Eating Syndrome (NES)

The human phenotype of a delayed pattern of eating is consistent with NES, defined by evening hyperphagia (i.e., consumption of greater than 25% of daily caloric intake after dinner) and/or nocturnal ingestions (i.e., waking during the sleep period to eat) at least twice per week. NES is positively related to BMI in some epidemiological and clinical studies, but not in others, particularly those that included higher proportions of young adults. While lower sleep efficiency (i.e., the ratio of the total time spent asleep compared to the total amount of time spent in bed) occurs in NES, sleep onset and offset are similar to those observed in control participants in inpatient and outpatient settings, even with increased caloric intake. Despite the lack of delayed sleep, persons with NES showed blunted peaks and troughs of the circadian rhythms of food intake, cortisol, ghrelin, and insulin, but increased thyroid stimulating hormone (TSH) amplitude during a 24-hour blood draw with ad lib food access. Those with NES also showed circadian phase delays of leptin, cortisol, insulin, and melatonin, with a circadian phase inversion of glucose and a phase advance in ghrelin. The phase advance of ghrelin was unexpected, but likely related to the ad lib food access allowing for nocturnal ingestions, which limited the overnight fasting period. Additionally, eating habitually during the night may re-program the stomach and gastrointestinal track to release ghrelin before a person’s usual time for nocturnal ingestions.

Results from other populations also strongly suggest that nighttime eating may contribute to weight gain or maintenance of higher weight. Gluck et al. provided food ad libitum to participants during a 3-day inpatient stay and found that those who ate between 2300h-0500h had higher 24-hour respiratory quotients and carbohydrate oxidation rates than those who did not eat during those hours.

Fortamet and Metformin: Considerations for Weight Loss and Diabetes Management

It is very important that your doctor check your or your child's progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects. This medicine may interact with the dye used for an X-ray or CT scan. Your doctor should advise you to stop taking it before you have any medical exams or diagnostic tests that might cause less urine output than usual. You may be advised to start taking the medicine again 48 hours after the exams or tests if your kidney function is tested and found to be normal. Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.

Important Precautions

Alcohol-Drinking alcohol may cause severe low blood sugar. Other medicines-Do not take other medicines unless they have been discussed with your doctor. Counseling-Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur with lifestyle changes, such as changes in exercise or diet. Travel-Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. In case of emergency-There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.

Read also: Inspiring Health Transformation

Under certain conditions, too much metformin (the active ingredient contained in Fortamet) can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear, and usually occur when other health problems not related to the medicine are present and are very severe, such as a heart attack or kidney failure. Symptoms of lactic acidosis include abdominal or stomach discomfort, decreased appetite, diarrhea, fast or shallow breathing, a general feeling of discomfort, severe muscle pain or cramping, and unusual sleepiness, tiredness, or weakness. If symptoms of lactic acidosis occur, you should get immediate emergency medical help. This medicine may cause some premenopausal women who do not have regular monthly periods to ovulate. This can increase the chance of pregnancy. If you are a woman of childbearing potential, you should discuss birth control options with your doctor. This medicine may cause hypoglycemia (low blood sugar). This is more common when this medicine is taken together with certain medicines. Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Talk to your doctor about the best way to treat low blood sugar.

Potential Side Effects

Along with its needed effects, metformin may cause some unwanted effects. Some side effects of metformin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine.

General adverse events include gastrointestinal events such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite have been frequently reported during therapy initiation and resolve spontaneously in most cases.

The Dangers of Hidden Ingredients in Weight Loss Products

The Food and Drug Administration (FDA) has issued numerous public notifications regarding weight loss products that contain hidden and potentially dangerous drug ingredients. These ingredients are often not listed on the product label, making it difficult for consumers to know what they are taking. The FDA advises consumers to be cautious of any weight loss product that promises rapid or dramatic results, as these products are more likely to contain hidden ingredients.

Examples of Products with Hidden Ingredients

The FDA has identified numerous weight loss products that contain hidden drug ingredients. Some examples include:

FATZorb
Toki Slimming Candy
LipoFit Turbo
THERMO SHOCK
ITCHA XS
Body Shape Weight Loss System
Govvi WOW!
Phentamene XT
NORF 20
Alfia Weight Loss Capsules
Lipopastilla + Gold Max
Dr. Reade Slim Sense
Hydro Pinapple [sic] Burn
Cholestene
Genesis Ultra Slim Gold
365 SKINNY High Intensity
Miss Slim
Tummy Tuck Max
Vy & Tea
Super Slim
Lishou Slimming Coffee
Li Da Daidaihua Plus
Imperla Elita Vitaccino
Fruta Planta
Fruta Bio
Burn 7
Livtone
Detox Plus
CholesLo
Skinny Pill
Lanugar
JaDera PLUS
Sheaya Lender
Love in S
Reduktis Max
Lipro Dietary Capsule
Adelgasin Plus
Super Slimming Herb
Lishou Fuling Jiaonang
Detoxi Slim
Absolute Nine Slim
GoLean Detox
Ultra Fit
Slimmer Extreme Thermogenic Formula
Slim Bio Capsules
Slimina
Pink Granada
Green Lean Body Capsule
Shengan Natural Model
Like Slim Coffee
In Shape
Baschi Quick Slimming Capsule
BodySlim Herbal
Easy 2 Slim
Slimming Capsule
Nuvitra
Asunsa
Lyn DTOX FS3
Adipotrim XT
Body Shape Weight Loss System
Row of Antibody Pil
Adriana Balance S
AB Slim
PAYA Dietary Supplement Product
Asia Slim Capsules
Adipessum Miracle Slimming Capsules
Fruta Planta Life (Garcinia Cambogia Premium)
A1 Slim
Physic Candy - Define
Physic Candy - Curve
Slimming Plus Advanced
Platinum Weight Loss Solution - Fat Loss Metabolizer
Platinum Max Strength Blue Pill Version
Lean Extreme Max
X-treme Beauty Slim
Queen Slimming Soft Gel
ABX Weight Loss
Supreme Slim 5.7
Ultimate Body Tox
Zi Su Body Fat Health II (Zi Su Shou Shen Ying Yang Su II)
Skinny Bee Diet
Results
Accelerator Boost
Natural Eruption
Citrus' Fit
Adelganzantes R-II
Zi Xiu Tang Beauty Face and Figure Capsule
Ultimate Lean
Slim Fit X
Maxx Easy
Mang Luk Power Slim
Mang Luk Power Slim Detox
Xcelerated Weight Loss Ultra Max
Xcelerated Weight Loss Turbo Charge
Xcelerated Weight Loss Charged Up
Dream Body Advanced Acai Weight Loss
Dream Body Extreme Gold
Dream Body Original Formula
Extra Slim Plus Acai Berry Weight Loss Formula
Exhilarate
Step 2
Black Label X
Black Gold X Advanced
3rd Degree
Propell Platinum
ENVY BP
ZlimXter Capsules
Xerophagy Capsules
Eradicate Capsules
Dynamizm Capsules
La'Trim Plus
Evolve Bee Pollen
Jenesis
Oasis Bee Pollen
Prime Bee Pollen
Thirty Plus
Lipo Escultura
Zero Fat
SPCARET Princess Diet
Slyn Both
Perfect Slim Fast Track Slim
Super Herbs
Xtreme Fat Burner Capsules
Tip-Top Shape
Lishou Slimming Coffee
Basha Nut 100% Fruit Soft Gel Capsules
Ultimate Herbal Slimcap
NATUREAL
Meizi Super Power Fruits Herbal Slimming Formula
Achieving Zero
Zero Xtreme Capsules
Akttive Capsules
Slim Forte Slimming Capsule
Li Da Dai Dai Hua Slimming Capsule
Fatloss Slimming Beauty
Superior
Green Algae Combination by Crane Beauty
Xcel Advanced
Xcel
Ultimate Boost
L-Carnitine Sob Strengthening Version Slimming Miracle Capsule
Black Mamba Hyperrush
Natural Max Slimming
Diablos Eca Fire Caps
Eliminating Weight
Oxy ELITE Pro Super Thermogenic
Nine Slim
Seven Slim
Botanical Slimming (Red)
Lean Body Extreme
Yanhee Slim
Slim-K
Slim-Vie
Super Extreme Accelerator
Japan Hokkaido Slimming Weight Loss Pills
Mix Fruit Slimming
Lingzhi Cleansed Slim Tea
24 Ince
Lipo 8 Burn Slim Capsules
Sliming (sic) Diet By Pretty White
Trim-Fast Slimming Softgel
Sport Burner
Toxin Discharged Tea
Sliming Diet
La Jiao Shou Shen
B-Perfect
Asset Bold
Asset Bee Pollen
Natural Body Solution
Slim Trim U
Lite Fit USA
Infinity
New You
Vitaccino Coffee
Citrus Fit Gold
Tonic Life BP
Thinogenics
Dream Body Slimming Capsule
Meizitang Citrus
Asset Extreme Plus
7 Days Herbal Slim
Dr. Ming's Chinese Capsule
SlimEasy Herbs Capsule
Sliming (sic) Diet Berry Plus
Asset Extreme
SlimExtra Herbal Capsules

Regulatory Actions

The FDA has taken action against companies that market weight loss products with hidden ingredients, including issuing warning letters, seizing products, and pursuing criminal charges. Despite these efforts, weight loss products with hidden ingredients continue to be sold online and in retail stores.

tags: #fortimed #weight #loss #ingredients