30th August 2024, A/Prof Chee L Khoo
Up until GLP1RAs +/- GIPs were shown to be efficacious in assisting patients lose weight and keeping the weight off, long term sustainable weight loss was practically unachievable. Not everyone wants to or is able to afford bariatric surgery to assist in weight loss. Even then, the weight loss is usually not sustainable. International guidelines (including Australian) include medical nutritional therapy in the management of obesity. In general, you need to be in calorie deficit if you want to lose weight and VLCD is one of those diets that are bandied around. Yet, there is a reluctance to prescribe VLCD to patients who may benefit from VLCD. Most dietitians are against this form of dieting. Most specialists are not that familiar and voice some concerns about its durability or safety.
What is VLCD?
On average, most of us need about 2000 calories daily to be calorie neutral. The threshold for delineating VLCDs from LCDs has typically been 800 kcal/day, with VLCDs having a prescribed energy intake of less than 800 kcals/day. LCDs utilise partial meal replacements (two meal replacements plus a energy limited meal) to achieve energy intake of 1000-1200 calories per day. VLCD usually require total meal replacements to achieve less than 800 calories per day.
The meal replacements can be products specifically marketed for weight loss, such as protein shakes or bars, or can be portion-controlled conventional/frozen foods. There are many different brands of these shakes each containing different nutrients which may or may not be suitable for various medical conditions e.g. diabetes or chronic kidney disease.
Many replacement meals have evolved to become high quality, nutrient-fortified formulations that can adequately meet recommended vitamin and mineral intakes for many adults consuming reduced-calorie meals.
Does VLCD work?
In the Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET) trial, 278 participants > 18 years old with a BMI > 30 underwent total diet replacement of 810 calories per day for 8 weeks followed by 12 weeks of one MR per day for 24 weeks (1). At 6 months, the TDR group lost 15.1 ± 8.7 kg, compared to 4.5 ± 6.2 kg for the controls. By 12 months, the TDR group maintained a weight loss of 10.7 ± 9.6 kg, which was 7.2 kg (95% confidence interval [CI] 4.9, 9.4) more than the control group.
In the Diabetes Remission Clinical Trial (DiRECT), participants aged 20–65 years, had a BMI 27–45 kg/m2, were not on insulin, and had diabetes for ≤ 6 years underwent TDR of 850 calories per day for 3-5 months followed by weight maintenance phase (2). The TDR diet group, achieving a mean weight loss of 10.0 kg, 24% of the intervention group achieved at least 15-kg weight loss compared to 0% in the control group; similarly, 46% of the intervention group achieved diabetes remission.
The OPTIWIN study, participants underwent TDR for 12-16 weeks followed by 1-2 MRs per day up to 52 weeks (3). Weight loss in the TDR group was 10.6. The proportion of participants who achieved ≥10% weight loss was 43.7% and 21.7% for TDR and the food-based diet, respectively. Both groups had comprehensive behavioural counselling with weekly group sessions and prescriptions for physical activity of 150–180 min per week of moderate to vigorous exercise.
The TEMPO study compared moderate energy restriction (25%–35% of estimated energy expenditure for 12 months) to TDR (65%–75% reduction TDR for 4 months) in post menopausal women (4). Both groups continued with moderate calorie restriction for 8 months. At least 10% body weight loss was achieved in 82% of TDR group. Both groups were prescribed protein intake of 1g/kg/day and physical activity target of 8000–12 000 steps/day, including 30–60 min/day of moderate to vigorous intensity activity.
The Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I) trial was the first RCT to test TDR in individuals from the Middle East and North Africa region (5). At 12 months, the TDR group had a weight loss of 11.98 kg compared with 3.98 kg in the control group. Diabetes remission was noted in 61% of intervention group participants compared to 12% remission in the control group.
There were other trials achieving similar results with TDR of various duration. Adverse events in the trials of TDR generally include mild to moderate severity adverse events that include symptoms such as constipation, fatigue, headache and dizziness.
There have been concerns that VLCD may lead to eating disorders but no evidence of causality or increased risk for the development of disordered eating behaviours in individuals being treated for obesity via calorie restricted methods.
How does VLCD work?
Weight loss with VLCD primarily works because to lose weight, one needs to be in calorie deficit. In addition to the rapid body weight loss, there is improvement in cardiovascular risks (BP, lipids), insulin sensitivity and pancreatic beta cell function. This can translate into better glycaemic control (HbA1c, fasting and post prandial glucose).
It is often mentioned that rapid weight loss is often not sustainable as rapid weight loss will generate an increase in hunger. Actually, several studies have shown that meal replacement used as part of a VLCD has been associated with reduced cravings, symptoms of hunger, and improved satiety during treatment (6-8). This is particularly true in replacements which are high in protein and low in carbohydrates.
The exact mechanisms responsible for reduced cravings, hunger, and improved satiety in the use MR as part of an LCD/VLCD are not known. It is possible that these findings are due to downregulation of reward and homeostatic regions of the brain that are known to drive food consumption (9-10). During a low-carbohydrate (LC) diet, an LC test meal elicited greater postprandial glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and peptide YY (PYY) but lower ghrelin compared with an isocaloric low-fat meal during a low-fat (LF) diet.
Other benefits
Weight reduction is a well-established means to reduce risk factors for cardiovascular disease beyond dysglycaemia, including blood pressure, lipids, and markers of inflammation. Not only can MR in VLCD lead to weight loss, nutritional composition of the MR diet can be effectively controlled to deliver high-quality nutrition in a way that optimises CVD risk markers.
By reducing glucose loads using a VLCD, blood glucose and insulin resistance can be changed in a matter of days. Reduction in IR reduces abnormal hepatic gluconeogenesis. Hepatic fat content decreases, VLDL triglyceride production and plasma triglyceride reduces.
In the post hoc analysis of the OPTIWIN trial, the TDR group had reductions of BP 3.5/2.6 mmHg, 0.14 mmol/L in low-density lipoprotein cholesterol and 0.28 mmol/L in triglycerides, along with an increase in HDL cholesterol of 0.11 mmol/L at 52 weeks. Overall, there was significant reduction in the ASCVD score in the TDR group.
One of the concerns of rapid weight loss achieved with TDR is severe energy restriction can lead to a significant proportion of the weight loss from lean compartments such as skeletal muscle and bone. However, MR diets can be an efficient way to achieve protein and optimal micronutrient intakes that help to mitigate loss of lean mass despite reduced energy consumption. In the TEMPO study, despite achieving great weight loss, the TDR group lost the same amount of muscles compared with the moderate energy restriction group.
The TEMPO study also provided an assessment of physical function using handgrip strength measurements. There were no significant differences between the treatment groups at the 12-month outcome assessment. The severe restriction group had no significant changes from baseline in handgrip strength.
We should not only think of VLCD for obesity, T2D, MASLD and CV risk management alone.
Weight loss utilising VLCD is also very useful:
- As an adjunct to incretin injection therapy
- Maintenance after incretin injections and after bariatric surgery
- Pre op preparation to bariatric surgery and joint replacements
- Infertility management in women with PCOS and
- Adolescent obesity management
We can see from the many clinical trials that VLCD is effective with minimal serious adverse effects and well tolerated. Most of these trials have 2-5 months of severe calorie restriction with full TDR followed by a period of less calorie restriction with gradual food reintroduction. Some trials incorporate lifestyle measures as part of the total management. VLCD often lead to significant weight loss early but on average the weight loss achievable is ~12kg. All these are very achievable in primary care.
References:
1, Astbury NM, Aveyard P, Nickless A, et al. Doctor referral of overweight people to low energy total diet replacement treatment (DROPLET): pragmatic randomised controlled trial. BMJ. 2018;362: k3760.
2. Lean MEJ, Leslie WS, Barnes AC, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lancet. 018;391(10120):541-551.
3. Ard JD, Lewis KH, Rothberg A, et al. Effectiveness of a total meal replacement program (OPTIFAST program) on weight loss: results from the OPTIWIN study. Obesity (Silver Spring). 2019;27(1):22-29.
4. Seimon RV, Wild-Taylor AL, Keating SE, et al. Effect of weight loss via severe vs moderate energy restriction on lean mass and body composition among postmenopausal women with obesity: the TEMPO diet randomized clinical trial. JAMA Netw Open. 2019;2(10):e1913733.
5. Taheri S, Zaghloul H, Chagoury O, et al. Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial. Lancet Diabetes Endocrinol. 2020;8(6):477-489.
6. Sumithran P, Prendergast LA, Delbridge E, et al. Ketosis and appetite mediating nutrients and hormones after weight loss. Eur J Clin Nutr. 2013;67(7):759-764.
7. Gibson AA, Seimon RV, Lee CMY, et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev. 2015;16(1):64-76.
8. Martin CK, O’Neil PM, Pawlow L. Changes in food cravings during low-calorie and very-low-calorie diets. Obesity (Silver Spring, Md). 2006;14(1):115-121.
9. Alonso-Alonso M, Woods SC, Pelchat M, et al. Food reward system: current perspectives and future research needs. Nutr Rev. 2015;73(5): 296-307.
10. Kahathuduwa CN, Davis T, O’Boyle M, et al. Effects of 3-week total meal replacement vs. typical food-based diet on human brain functional magnetic resonance imaging food-cue reactivity and functional connectivity in people with obesity. Appetite. 2018;120:431-441.