DIABETES REMISSION IS NOW WITHIN REACH
L-Nutra Health for Diabetes is a whole new category of cutting edge nutri-technology intervention that unlocks the body’s own rejuvenation system to reduce medications and bring diabetes remission within reach.
Background
Type 2 diabetes is one of the most prevalent and costly chronic illnesses, which accounted for 6.7 million deaths worldwide in 2021 1 . Over 700 million people are expected to suffer from the disease by 2045. In the U.S., one out of every four dollars in health care costs is spent on caring for people with diabetes, which affects 37.3 million people 2 . Despite advances in new diabetes medications over the last decade, glycemic control disappointedly declined in U.S. adults with diabetes 3 .
In the face of these mounting challenges, L-Nutra is introducing a paradigm shift in diabetes care. L-Nutra Health for Diabetes aims to help people with type 2 diabetes thrive without medication through precision nutrition that reverses insulin resistance, inspires better behavioral habits, protects metabolic rate and muscle function while positively impacting their biological age to enhance their healthspan. At L-Nutra, we view diabetes as an urgent multi-organ system disease requiring prompt interventions so remission and/or regression can take place before permanent beta-cell and end-organ damage occurs, turning diabetes into a progressive chronic illness.
We’re spearheading a global movement to turn sick care into health care with NIH funded discovery and invention developed at the University of Southern California. We believe science should treat the source, not the symptoms. We believe food – one of the few things you consume continually – is the key to health, longevity and preventing and curing disease. We’re using groundbreaking science and natural, plant-based solutions to prove it. We believe these solutions - combined with AI technology, lifestyle education and health professionals - can help everyone live healthier and longer. In short, we’re here to change the world and usher in an entirely new kind of proactive health care, starting with diabetes.
First Systemic Solution for Diabetes: Program Approach and Rationale
The current standard of diabetes care emphasizes medical nutrition therapy with a focus on weight management through chronic caloric restriction, physical activity, and behavioral changes as part of a lifestyle modification strategy 4 However, in our current environment, adhering to the lifelong dietary measures required to mitigate the metabolic disorder of type 2 diabetes is difficult to sustain and may have detrimental consequences. Consequently, nutritional research has begun to shift its focus to other dietary patterns, such as the various forms of fasting, in shaping weight control, disease management, and longevity 5 .
Fasting lasting longer than two consecutive days, also known as periodic fasting, triggers, systemic response that activates cellular stress resistance and rejuvenation, and optimizes metabolism 6 Preclinical and clinical studies with periodic fasting increasingly demonstrate
its potential for disease modification in obesity, diabetes, autoimmune diseases, cancer, and neuro-degenerative disorders 7-9 . However, prolonged water-only fasting, despite its potential benefits, is difficult or unsuitable to implement for individuals with health conditions. Due to the inherent difficulties in adhering to prolonged periods of fasting, intermittent fasting (IF) regimens have become more popular and may be followed with better compliance 10 . However, periodic fasting has distinct benefits that cannot be realized by shorter duration variants of IF 5
To address the difficulty and potential risks of water-only fasting for 4 or more consecutive days, Professor Valter Longo at the University of Southern California (USC), with the support of the National Institutes of Health (NIH), developed the Fasting Mimicking Technology (FMT) platform and Longevity Nutrition. The Fasting Mimicking Diet (FMD) includes scientifically formulated and clinically tested foods that can be consumed while allowing the body to remain in a fasting state, allowing the person to experience comparable benefits associated with fasting. Research on FMD indicates that the intervention targets multiple organs related to diabetes pathophysiology, including fat, muscle, brain, liver, kidney, and potentially pancreatic beta-cells imparting upstream, systemic, and integrative beneficial effects. The diabetes studies detailed later in this dossier were conducted at leading academic centers such as the University of Heidelberg, Leiden University, and the University of Southern California. FMD, backed with substantial preclinical and clinical evidence and associated patents, is truly a unique market differentiator, offering a competitive advantage that cannot be replicated.
Targeting a New Diabetes Outcome
Recently, major medical associations around the world have begun to recognize that improvement of glucose levels into the normal range can be achieved in some people living with diabetes, either spontaneously or after specific interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy 11. These associations include the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK. The American College of Lifestyle Medicine, along with the American Association of Clinical Endocrinology, the Academy of Nutrition and Dietetics, and the Endocrine Society have jointly published an expertise consensus statement explicitly calling for using dietary interventions to treat type 2 diabetes in adults with a goal of remission12 Remission, according to the new consensus, is defined as a return of HbA1c to less than 6.5% that occurs spontaneously or following an intervention and that persists for at least three months in the absence of usual glucose-lowering pharmacotherapy. L-Nutra’s L-Nutra Health for Diabetes builds on the guidelines from the new consensus and aims to employ various fasting-mimicking interventions with pescatarian- or plant-based nutrition approaches to drive type 2 diabetes regression and remission.
L-Nutra is the first company to combine both products and services, compared to competitors who only offer a product or a service in its unique solution to drive diabetes into remission.
FMD Nutrition Formulation and Administration
FMD Nutrition is a specially formulated FMD for diabetes and the metabolic restoration of the body. It is a fasting-mimicking nutrition kit that comes in 5 daily boxes, including gluten-free plant-based energy bars, soups, a variety of snacks and drinks, and supplements, all designed and studied to nourish the body during the fast.
Physiological Changes during 5 day FMD Nutrition:
FMD Nutrition provides approximately 4600 kJ (1100 calories) on Day 1 (11% protein, 46% fat, and 43% carbohydrate) and approximately 3000 kJ (720 calories; 9% protein, 44% fat, and 47% carbohydrates) on days 2–5. All program foods and supplements are included in the kit; water is the only addition to complete the diet. The omega-3 supplement is derived from algae and is suitable for vegetarians.
Transition Diet/Re-feeding Period (not included in the kit)
Upon completion of the FMD Nutrition cycle, binge eating should be avoided. The program member is to gradually resume a normal diet, starting with liquid food such as soup, then light meals including brown rice and whole wheat pasta, and small portions of fish, meat, and/or legumes. A regular, healthy diet is resumed on Day 7.
The Longevity Diet
For the days in-between each FMD Nutrition cycle, the program members will be advised to follow the Longevity Diet. The diet embraces the nutritional principles outlined in the Longevity Diet book 13 , authored by Professor Valter Longo at USC. Studies on aging and the link between diet and longevity have identified feasible nutritional strategies, which have been integrated to define a longevity diet. These nutritional strategies have been shown to delay aging and/or prevent diseases 5 . The Longevity Diet is characterized by a moderate to high carbohydrate and a low but sufficient protein (mostly plant-based) intake. It emphasizes five nutritional strategies, including: 1) lots of legumes, whole grains, and vegetables; 2) regular consumption of fish and vegetable-derived proteins; 3) no red or processed meat and very low white meat; 4) low sugar and refined grains; and 5) Include nuts, olive oil, and some dark chocolate. Although limiting daily eating within a 12-hour window is recommended, Longevity Nutrition is not a dietary restriction intended to only cause weight loss. Rather, Longevity Nutrition is a lifestyle focused on promoting healthspan, which can complement standard healthcare to aid in ameliorating morbidity and sustaining health.
In addition, L-Nutra offers other FMD products including Fast Bar™ (with a Glycemic Index of 25) 14 and Fast Shake™, both of which are specially formulated with energy content and macronutrient composition that extend physiological ketogenesis similar to fasting, while providing some energy and nutrients to increase the sense of fullness and satiety. L-Nutra will soon be launching a Longevity Shake™ aimed to provide nutrition that helps maintain muscle mass without spiking the insulin and IGF-1 levels.
Difference between Fasting Mimicking Diet & Ketogenic Diet
Fasting results in a progressive selection of fat as body fuel. After a meal, glucose is used for energy or converted for storage as glycogen or triglycerides. Fasting leads to the mobilization of hepatic glycogen stores. As the hepatic glycogen stores are being spent (after 8–18 hours of fasting), the body starts breaking down protein and then fat to produce ketones as an energy substrate for peripheral tissues. Individuals with higher BMI values may take longer to reach ketosis. Fat provides more than 75% of the calories utilized after the first few days of fasting. The associated progressive decrease in daily urinary nitrogen excretion suggests an increasing conservation of protein 15 Ketoacid levels in the blood become elevated over the first week, and the brain preferentially uses these compounds instead of glucose. The net effect is to spare protein even further as glucose availability is diminished.
Born as an alternative therapeutic strategy for refractory epilepsy, the classic ketogenic diet (KD) is characterized by a low-protein, low-carbohydrate, and high-fat dietary regimen (90% fat). Although KD simulates the metabolic fasting response, patients could have variable
responses to these dietary regimens 16 . KD is not a physiological diet. Supplementation is essential, and patient compliance presents as an issue 17 . Indeed, chronic KD is difficult to manage because of eventual unpalatability and adverse effects, including hyperuricemia, hypocalcemia, hypomagnesemia, nephrolithiasis, and ketoacidosis 16 . Additionally, due to the protein content, ketogenic diets trigger nutrient-sensing pathways in the cells, providing growth signals instead of activating cellular protective and restorative pathways associated with fasting. FMD Nutrition provides primarily plant-based and scientifically formulated ingredients characterized by a low-protein content. It does not contain additives, preservatives, or chemicals. It nourishes the body while providing many of the benefits of prolonged fasting. FMD is designed to put the body’s cells into a fasting state, which inhibits cellular growth and activates a stress-resistant state, allowing cells to undergo autophagy and rejuvenation, thus supporting multisystem renewal. In a study of generally healthy subjects, serum ketone bodies increased 3.2-fold at the end of the FMD regimen (p <0.001) and returned to baseline levels following normal food intake 18 . FMD Nutrition includes food item enhancements to induce cells to enter a state of metabolic fasting while protecting lean body mass 19 . FMD Nutrition leads to upstream and systemic effects and appears to have broader therapeutic potential when properly used as dietary support in certain disease states.
Program Description
L-Nutra Health for Diabetes is a 12-month metabolic restoration program, based on the proprietary Remission and Regression (R-R) Protocol, designed for individuals with type 2 diabetes who are not merely satisfied with keeping their glucose levels in control with pharmaceuticals but want to get their diabetes into remission without surgery, medications, or jeopardizing their long-term health. L-Nutra is launching the Program as the full-suite solution partner for health care professionals (HCPs) who want to safely deprescribe medications and help their patients reverse diabetes through a combination of sciencebacked fasting nutrition and Longevity Nutrition under the guidance of a registered dietitian who is trained in metabolic and longevity science.
The HCP enrolls suitable patients and is responsible for medical supervision, medication adjustment, and quarterly laboratory monitoring. A registered dietitian from the Program, who serves as the patient navigator and coach, provides personalized consultations for nutrition and behavioral support, gathers and interprets information from connected health devices, and liaises with the HCPs. The customized nutrition interventions consist of the following:
• A 6-month active phase, which taps into 6 cycles of monthly 5-day Fasting-Mimicking Diet (FMD), to kickstart metabolic, cellular, emotional, and behavioral changes
• A plant- or pescatarian-based Longevity Nutrition eating plan implemented by the dietitian coach
• The recommended Time Restricted Eating (TRE), which involves food consumption for 12 hours a day and fasting periods of 12 hours per night during the Program
Following the 6-month R-R Protocol, the Diabetes Expert Care Team from the Program regularly monitors the progress and tailors the intervention. When clinically indicated, the dietitian coach directs members to the maintenance phase, where the frequency of the FMD is reduced to every three months and the Longevity Nutrition is continued based on the patient’s need and preference.
L-Nutra Health for Diabetes
A unique FMD formulation scientifically developed specifically for people with Type 2 Diabetes
The Program provides a bluetooth-enabled bioimpedance scale to track anthropometric changes. The Diabetes Management (DM) app further supports comprehensive diabetes education, communication, data collection, and in-app product fulfillment. In addition to FMD, members receive one round of the Longevity Nutrition meal package. Through this trial, members have the option to purchase the ready-to-eat Longevity Nutrition meal package delivered by N4L (https://nutritionforlongevity.com/)
References
1. IDF Diabetes Atlas, <https://diabetesatlas.org/> (08/01/2020).
2. Cost-Effectiveness of Diabetes Interventions, <https://www.cdc.gov/chronicdisease/programsimpact/ pop/diabetes.htm> (08/01/2022).
3. Fang, M., Wang, D., Coresh, J. & Selvin, E. Trends in Diabetes Treatment and Control in U.S. Adults, 1999-2018. N Engl J Med 384, 2219-2228, doi:10.1056/NEJMsa2032271 (2021).
4. Evert, A. B. et al. Nutrition Therapy for Adults With Diabetes or Prediabetes: A Consensus Report. Diabetes Care 42, 731-754, doi:10.2337/dci19-0014 (2019)
5. Longo, V. D. & Anderson, R. M. Nutrition, longevity and disease: From molecular mechanisms to interventions. Cell 185, 1455-1470, doi:10.1016/j.cell.2022.04.002 (2022).
6. de Cabo, R. & Mattson, M. P. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med 381, 2541-2551, doi:10.1056/NEJMra1905136 (2019).
7. Nencioni, A., Caffa, I., Cortellino, S. & Longo, V. D. Fasting and cancer: molecular mechanisms and clinical application. Nature reviews. Cancer 18, 707-719, doi:10.1038/s41568-018-0061-0 (2018).
8. Di Francesco, A., Di Germanio, C., Bernier, M. & de Cabo, R. A time to fast. Science 362, 770-775, doi:10.1126/science.aau2095 (2018).
9. Mattison, J. A. et al. Caloric restriction improves health and survival of rhesus monkeys. Nature communications 8, 14063, doi:10.1038/ncomms14063 (2017).
10. Barnosky, A. R., Hoddy, K. K., Unterman, T. G. & Varady, K. A. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings. Transl Res 164, 302-311, doi:10.1016/j.trsl.2014.05.013 (2014).
11. Riddle, M. C. et al. Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes. Diabetes Care, doi:10.2337/dci21-0034 (2021).
12. Rosenfeld, R. M. et al. Dietary Interventions to Treat Type 2 Diabetes in Adults with a Goal of Remission: An Expert Consensus Statement from the American College of Lifestyle Medicine. Am J Lifestyle Med 16, 342-362, doi:10.1177/15598276221087624 (2022).
13. Longo, V. The Longevity Diet. (Penguin, 2018).
14. Huang, A. W. et al. An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study. Nutrients 13, doi:10.3390/ nu13051523 (2021).
15. Cahill, G. F., Jr. Starvation in man. N Engl J Med 282, 668-675, doi:10.1056/NEJM197003192821209 (1970).
16. Schugar, R. C. & Crawford, P. A. Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care 15, 374-380, doi:10.1097/ MCO.0b013e3283547157 (2012).
17. D'Andrea Meira, I. et al. Ketogenic Diet and Epilepsy: What We Know So Far. Front Neurosci 13, 5, doi:10.3389/fnins.2019.00005 (2019).
18. Wei, M. et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med 9, doi:10.1126/scitranslmed.aai8700 (2017).
19. Nardon, M., Venturelli, M., Ruzzante, F., Longo, V. D. & Bertucco, M. Fasting-Mimicking-Diet does not reduce skeletal muscle function in healthy young adults: a randomized control trial. Eur J Appl Physiol 122, 651-661, doi:10.1007/s00421-021-0486