Obesity has reached epidemic proportions in the US. Maintaining weight loss is important for the management of many of the complications of obesity, including reductions in blood pressure, glucose, and insulin concentrations, and may reduce the risk of diabetes and all-cause mortality. Due to adaptive physiological changes that occur following weight loss, as well as the need for continued implementation of positive diet and lifestyle changes, maintaining long-term weight loss can be a challenge, and the odds of weight regain are very high. Significant research efforts have focused on strategies that would promote weight-loss maintenance.
This article delves into the role of Metagenics and nutritional strategies in weight loss, drawing on various research studies and expert opinions. We will explore the effectiveness of meal replacements (MRs), the impact of dietary patterns, and the potential benefits of multivitamin-multimineral supplements combined with bioactive phytochemicals.
The Role of Meal Replacements in Weight Loss
Meal replacements (MRs) are products intended to replace an entire meal. Forms of MRs usually vary from shakes, powdered shake mixes, bars, or soups. MRs are different from protein supplements in that they provide a range of macro- and micronutrients that would otherwise be found in a meal.
MRs vs. Conventional Low-Calorie Diets
In a meta-analysis of 6 weight loss studies that compared MRs in a structured meal plan with a conventional LCD plan (the calorie intake was the same for both plans), greater total weight loss was achieved with MRs in a structured meal plan at 3 months (7% vs. 4%) and 12 months (7-8% vs. 3-7%) than with a conventional LCD plan. Additionally, the number of participants experiencing total weight loss of ≥ 5% was significantly higher with MRs in a structured meal plan compared with a conventional LCD plan at 3 months (72% vs. 34%) and at 12 months (76% vs. 45%).
The Impact of MR Intake on Weight Loss Goals
The Look AHEAD study found the number of MRs consumed as part of a structured intervention was significantly related to total weight loss at 6 and 12 months. Participants with highest MR intake had 4.0X greater odds of reaching the 7% total weight loss goal and 4.1X greater odds of reaching the 10% total weight loss goal than participants with lowest intake.
Read also: Weight Loss Guide Andalusia, AL
Calorie Consumption and MRs
Controlled feeding studies have shown that when a MR is consumed at lunch, ~250 fewer calories were consumed than when lunch was chosen freely by participants.
Dietary Patterns and Weight Management
People do not eat individual nutrients; they consume dietary patterns with varying diet quality. To that end, Dr. Hu presents dietary patterns and components of those patterns that are associated with increased vs. decreased risk of weight gain and cardiometabolic diseases.
Dr. Frank Hu's Perspective
In this presentation, “The Cardiometabolic Consequences of Obesity and Nutritional Strategies for Prevention,” Frank Hu, MD, PhD, reviews high-quality research demonstrating the dietary contributors to weight gain and the impact of overweight/obesity on cardiometabolic diseases and mortality.
Multivitamin-Multimineral Supplements and Phytochemicals
A multivitamin-multimineral supplement combined with a diverse blend of bioactive phytochemicals may provide additional antioxidant capacity and anti-inflammatory property for overall health.
Pilot Study Design and Methodology
We conducted a pilot study in 15 healthy individuals (8 women and 7 men, mean age 41.7±14.9 years, mean body mass index 28.0±5.6) to investigate the effects of this novel formulation on biomarkers associated with oxidative stress and inflammation. Eligible participants were men and women between 18 and 65 years of age (inclusive) who were willing to maintain current exercise practice and to adopt the study diet. Main exclusion criteria included (1) use of nutritional supplements, medications (narcotics, corticosteroids, NSAIDs, aspirin, and COX-2 inhibitors), drugs of abuse, and special food plans within 2 weeks prior to the study, (2) history of cardiovascular, renal, hepatic, and autoimmune disease, (3) history of allergy or intolerance to study products, (4) weight loss of ≥10% of total body weight within 6 months prior to the study, and (5) pregnancy or breast-feeding. The research was carried out in compliance with the Helsinki Declaration of 1975, and the study was approved by the Copernicus Group Independent Review Board (Durham, North Carolina). The pilot study employed a one-group pre-post design. At Visit 1 (Week 0), participants were instructed to begin a 2-week diet-only phase that limited intake of fruits and vegetables to a total of 2 servings/day (Table 1). At Visit 2 (Week 2), participants continued with the same restricted diet (Table 1) but were instructed to begin consuming 2 tablets of the study product every morning with a meal for the subsequent 4 weeks. The study product is a commercially available nutritional supplement containing multivitamins, multiminerals, and a diverse blend of phytochemicals (Table 2). Compliance with protocol was monitored at Visit 3 (Week 6) by count of remaining study product and evaluation of diet diaries. At Visit 2 and Visit 3, fasting blood samples were obtained, separated, and stored at −40°C prior to analysis. At each visit, the study investigator performed a clinical evaluation and recorded any adverse event.
Read also: Beef jerky: A high-protein option for shedding pounds?
Biomarker Analysis
Plasma carotenoids were analyzed at the Department of Nutritional Sciences, University of Connecticut (Storrs). Plasma levels of folate, vitamin B12, homocysteine, F2-isoprostane, and hsCRP were analyzed at the Cleveland HeartLab, Inc (Ohio). Serum levels of oxLDL, PAI-1, and MPO were analyzed at the MetaProteomics, LLC (Gig Harbor, Washington). EndoPAT was analyzed at the Functional Medicine Research Center (Gig Harbor). Plasma carotenoids were quantified using HPLC-UV method as previously described. Plasma folate and vitamin B12 levels were quantified using electrochemiluminescence immuno-assay (Cobas 6000 analyzer, Roche Diagnostics, North America). Plasma homocysteine levels were measured using an enzymatic method (Diazyme Laboratories, Poway, California). Serum oxLDL levels were measured using a solid phase two-site oxLDL ELISA Kit from Mercodia according to manufacturer's instruction. Serum PAI-1 levels were measured using a solid phase PAI-1 Human ELISA Kit from Invitrogen (Camarillo, California) according to the protocols provided by the manufacturer. Serum MPO levels were measured using a solid phase two-site MPO ELISA Kit from Mercodia (Uppsala, Sweden) according to the instruction provided by the manufacturer. F2-isoprostane was measured using a proprietary LC MS/MS method. hsCRP was measured using an immunoturbidimetric method (Roche Diagnostics, North America). EndoPAT (Itamar Medical LLC, Caesarea, Israel) was used to examine endothelial function. Reactive hyperemia was induced subsequent to upper arm occlusion of blood flow, and the reactive hyperemia index (RHI) was calculated using the ratio between digital pulse volume during reactive hyperemia and at baseline. For all biomarkers, changes from Visit 2 (baseline) to Visit 3 (end of treatment) were analyzed using paired t-tests with Excel (Microsoft, Redmond, Washington). Data were reported as mean ± standard error (SE).
Pilot Study Results
All 15 participants, including 8 women and 7 men, completed the pilot study. Their average age (mean ± standard deviation) was 41.7 ± 14.9 years old, and their body mass index was (BMI) 28.0 ± 5.6 kg/m2. After 4 weeks of supplementation with the study product, plasma concentrations of carotenoids, folate, and vitamin B12, but not homocysteine, were significantly increased compared with baseline (Table 3). Significant reduction in oxLDL was observed from 54.0 ± 3.3 U/L at Visit 2 to 45.0 ± 2.9 U/L at Visit 3 (Figure, P<.01). Similarly, PAI-1 was significantly reduced from 5914 ± 243 pg/mL to 4499 ± 194 pg/mL (P<.01), and MPO from 236 ± 24 µg/L to 165 ± 21 µg/L (P<.01). F2-isoprostane was not significantly different between Visit 2 and Visit 3 (0.40 ± 0.05 ng/mg and 0.40 ± 0.08 ng/mg, respectively), and neither was hs-CRP (2.9 ± 0.9 mg/L and 2.1 ± 0.6 mg/L, respectively). RHI was 1.87 ± 0.10 at Visit 2 and 1.97 ± 0.21 at Visit 3. AI was 10.81 ± 4.96 at Visit 2 and 11.53 ± 4.13 at Visit 3. Serum levels of oxidized low-density lipoprotein cholesterol (oxLDL), plasminogen activator inhibitor-1 (PAI-1), and myeloperoxidase (MPO) at Week 2 and Week 6. *P<.01.
Adverse Events
Throughout the study, 8 subjects reported a total of 13 mild, self-limited adverse events. Nausea (n=3), abdominal discomfort (n=2), and vomiting (n=1), appeared related to having taken the study product without food.
Implications of the Study Findings
The 4-week use of the phytochemical-multivitamin-multimineral formulation resulted in increased circulating levels of carotenoids, folate and vitamin B12, and decreased circulating levels of oxLDL, PAI-1 and MPO in this open-label pilot study. Excessive environmental toxins and endogenous production of reactive oxygen species can damage biomolecules such as DNA and LDL. Oxidative modification of LDL-and the formation of oxLDL-can generate more free radicals and contribute to inflammatory processes and hence the pathogenesis of atherosclerosis.
The Role of oxLDL, MPO, and PAI-1
As circulating oxLDL levels correlate with cardiovascular events, reducing oxLDL may prevent or delay the development of atherosclerotic lesions and other metabolic abnormalities. We also observed a significant reduction in MPO in our study participants. The enzyme MPO is the major protein of neutrophils and key to innate immunity. Secreted by activated neutrophils, MPO generates various reactive species such as hypochlorous acid that eradicate invading pathogens. As MPO is released into the extracellular space, it may also interact with LDL and oxidize the circulating lipoprotein and form MPO-dependent oxLDL. Recent research has in fact identified MPO-dependent oxLDL to be more atherogenic than oxLDL generated by other oxidative processes. Epidemiological studies have shown that increased plasma levels of MPO are predictive of endothelial dysfunction and other adverse cardiac outcomes and low plasma levels of MPO are protective against cardiovascular damage. Therefore, reducing MPO levels may reduce cardiovascular disease (CVD) risk.
Read also: Inspiring Health Transformation
The adipokine PAI-1 is the most potent inhibitor of fibrinolysis. The presence of low-grade inflammation has been shown to induce the gene expression of PAI-1 in adipose tissue followed by increased levels of PAI-1 in circulation. The resulting impairment of fibrinolysis increases vascular deposition of fibrinous products and promotes the progression of vascular disease. Indeed, elevated levels of PAI-1 have been observed in individuals with insulin resistance, type 2 diabetes, obesity, and other prothrombotic conditions. Hence, lowering PAI-1 may decrease CVD risk. Our pilot study showed that the phytochemical-rich MVMM significantly reduced PAI-1 levels.
Comparison with Other Studies
Similar findings have been observed in other nutrition studies. For example, oral supplementation of 77.7 mg/day rosemary extracts (containing carnosol, carnosic and rosmarinic acid) decreased PAI-1 levels in healthy young participants after 21 days. In a randomized controlled trial, patients undergoing primary prevention of CVD received a resveratrol-containing grape extract (8 mg/ day of resveratrol) for 1 year, and their PAI-1 levels were significantly reduced at the end of the trial. Interestingly, that study demonstrated that the resveratrol-containing grape extract was effective whereas the grape extract without resveratrol was not. However, not all similar nutrition studies have shown efficacy in lowering PAI-1.
Endothelial Function and EndoPAT
In terms of measurements of endothelial function, the EndoPAT was developed to overcome the technical disadvantages of conventional ultrasound measurement such as flow-mediated vasodilation. Data from Framingham Third Generation Cohort participants revealed that EndoPAT's RHI was inversely associated with multiple CVD risk factors. Clinical studies have also shown that dietary flavonoid intervention improved endothelial function as determined by the EndoPAT. We did not see statistically significant changes in RHI and AI (nor in hs-CRP and F2-isoprostane) in this study. These results are not surprising, for the participants were all healthy and their baseline levels of these measures were within normal ranges. According to Cleveland HeartLab, Ohio, hs-CRP of 1.0mg/L to 3.0 mg/L is associated with moderate cardiovascular risk and F2-isoprostane/creatinine ratio of <0.86 ng/mg is considered to indicate low risk.
Limitations of the Pilot Study
Although the favorable results of our pilot study are encouraging, we acknowledge that there are several limitations. First, the lack of a randomized control arm, short study length, and small sample size would limit the generalizability and validity of our findings. Second, we explored only a small number of biomarkers of oxidative stress, inflammation, and CVD risk, and therefore do not know if other relevant markers-endogenous antioxidants, TNF-α, intercellular adhesion molecule-1, vascular adhesion molecule-1, flow-mediated vasodilation, etc-would have been affected by the supplementation in a consistent direction. Third, participants received dietary instructions but were not strictly controlled and monitored; unknown dietary deviations or changes in micronutrient or macronutrient intake might have confounding effects. Fourth, MPO and PAI-1 are markers commonly used in scientific research; their utility as a mainstream therapeutic or diagnostic tool has yet to be established. Last but not least, our study participants are healthy; therefore, how high(er)-risk patients would respond to the study MVMM remains to be investigated. Nevertheless, since the majority of MVMM users take supplements to improve overall health early on, we believe our pilot study in healthy individuals is relevant.
tags: #metagenics #weight #loss #research