Book Questions

What was the most significant discovery from your research group related to metabolism?

In 2009 our group identified specific genes that are altered by a high-carb, high-fat diet.This gene array included all relevant pathways in muscle and adipose tissue, including Fatty acid biosynthesis.

Fatty Acid Metabolism covering nearly the entire mouse genome, is posted on the wall here at the lab. But then we went two steps beyond that, testing thousands of plant compounds for their ability to RESTORE normal metabolic pathways that control fat-burning and glucose disposal. If either of those were successful, that would be a breakthrough, but we accomplished BOTH.

The active ingredient in Level G (known as UP-780) was shown – in two human clinical trials (one published in FASEB) to upregulate fat-burning and dramatically improve glucose disposal, resulting in a remarkable drop in triglycerides, and improvements in fasting glucose, insulin, HgbA1C and biomarkers relating to oxidative stress.

What’s the connection between The Metabolic Makeover and the condition called Metabolic Syndrome?

Metabolism is the complex series of biochemical reactions that maintain life. The Metabolic Makeover was designed to support and enhance metabolic functions related to energy balance; basically, what happens to the food we eat, and how those molecules are burned, stored and transported. Obviously, all of these factors play key roles in the dysregulation of energy balance, known as Metabolic Syndrome. But the research was not designed to treat that constellation of symptoms.

We create energy all the time; some from sugars and starches derived mainly from the carbohydrates we eat. We also create energy from burning fat. In fact, each person burns a mix of fat and sugar. This is called energy balance. Not surprisingly, this balance – how much sugar and how much fat we are burning – has a tremendous effect on our body composition, exercise tolerance, mood, and overall health.

For more than 20 years, the research group that I am associated with – known as ECONET- investigated the effect of natural products on energy balance. With advanced genomic technologies, we identified plant compounds that can help support normal glucose and fat metabolism. Then, a human clinical trial was conducted at a leading university, UC Davis Medical Center, showing significant benefits derived from these all-natural compounds . Importantly, this research was presented at an international scientific symposium and published in two peer-reviewed biomedical journals.[1],[2]

Physicians using the Metabolic Makeover are documenting improvements in serum lipids, fasting glucose and insulin, exercise tolerance and carbohydrate cravings. Over time, these benefits translate to a restoration of energy balance and improvements in Metabolic Syndrome. Since increased activity and improved energy balance can lead to weight loss, the Metabolic Makeover has also been producing improvements in body composition.

It is our belief that improving the muscle to fat ratio is the key to restoring normal metabolic function. Failing that, the health care provider has to resort to a drug-only approach that is NOT geared to resolution of the condition, but management of the symptoms. Thus a patient with this common disorder might be placed on 6 or more drugs. A diuretic, beta blocker and ACE inhibitor for their blood pressure, a sulfonylurea (eg glyburide), a biguanide (eg Metformin) and a TZD (eg Actos) for their blood sugar, and a statin (with or without a fibrate) to lower their cholesterol and LDL.

Watching the on-going news reports of adverse drug effects, it is no surprise that increasing numbers of patients are seeking natural alternatives. This presents a problem for the physician who is expected to produce rapid improvements in critical biomarkers. The natural product arena, however, generally lacks the kind of scientific support that physicians need in order to provide best care. Both patients and physicians want safety AND efficacy.

The Metabolic Makeover provides health care professionals with a documented, carefully researched program. Not a “magic bullet” panacea approach, but one that addresses virtually every aspect of energy balance. With improved exercise tolerance and reduced carbohydrate cravings, patients are far more likely to follow their physician’s diet and exercise recommendations. In other words, patients on the Metabolic Makeover are more likely to comply with healthy lifestyle recommendations, bringing them closer to resolution, not just management, of their metabolic dysfunction.

[1] Sridevi Devaraj, Rohan Jialal, Ishwarlal Jialal, and Jason Rockwood Effect of Aloe vera Supplements in Patients with Pre-Diabetes FASEB J. 23: 900.7

[2] Get ref from Metabolic Syndrome and Related Disorders

How long before my patients see results?

Positive physiological change, especially involving diet and lifestyle factors, takes time. The average adult is replacing approximately 300 billion cells a day, which means that we all have a remarkable opportunity to build a body that looks, feels, and performs better than we presently do. But this cannot happen overnight. These benefits are cumulative; some may be felt within a matter of days, but the rest unfold over a period of weeks or months.

For validation of biomarker changes, you may use a conventional blood chemistry, or select from a growing number of comprehensive metabolic assessments. Physicians sometimes retest after 60 days in order to demonstrate efficacy to the patient, but in many cases, the benefits are already obvious. In any event, retest at 90 days provides valuable evidence of efficacy for doctor, patient and insurance carrier.

Details (for the science geeks)

1. High carbohydrate diet + sedentary lifestyle + genetic factors -> insulin resistance, dyslipidemia, diabesity. In this state, exercise tolerance (already compromised due to sedentary lifestyle) falls to a state where exercise is nearly impossible.

2. Reduced respiratory efficiency (chest wall breathing, poor circulation) contributes to systemic acidosis and increased oxidative stress.

3. Inflammation and oxidative stress -> downregulation (at transcription and tissue level) of signaling molecules that COULD restore homeostasis, eg adiponectin, GLUT4, AMPK, sirtuins.

First things First

We have to start thinking of Metabolic Syndrome as a process, and intervene as early as possible with safe and effective means to improve insulin sensitivity, blood lipids and energy balance. Patients are appropriately wary of a treatment plan that only includes additional drugs at every visit. The integrative approach, in which natural products are used first and pharmaceuticals added when necessary, is not only patient-friendly, but more effective in the long run.

The Metabolic Makeover takes advantage of the inter-relationship between oxidative stress (OS), inflammation, aging and insulin sensitivity. There is a close relation between OS and the metabolic control of diabetes, indicated by the levels of HbA1c. In fact, these are closely related processes, as demonstrated by the positive correlation between the rate of superoxide release from PMN’s and blood levels of HbA1c in type 2 diabetic patients.[1] The causative effect of OS on HbA1c in diabetes was previously reported in animals[2] and humans.[3] But the cycle of inflammation and oxidative stress, and its accelerating effect on glycol-oxidation of proteins, begins long before the diabetic state.

OS/ Inflammation à endothelial damage, atherosclerosis The Metabolic Makeover addresses all three system failures.

A. Upregulates genes associated with restored energy balance. In fact, comprehensive gene array analysis of mice fed a high fat diet indicates a general reversal of diet-induced epigenetic changes.

In Chapter 8, we list the Metabolic Modifiers that have been found to be most effective.

B. Optimal results can only be achieved by concomitant reduction of inflammation and oxidative stress. Botanicals like scutellaria, acacia, boswellin, hops and curcumin have been shown to downregulate IL-1 beta, TNF alpha, NF Kappa B and IL-6 in tissues where these inflammatory cytokines are overexpressed.[4]

C. Improved fat-burning -> greater and more consistent energy -> increased exercise tolerance. Reduced inflammation provides for increased joint comfort and range of motion. Leading to the performance of aerobic and resistance training.

D. Improved diet, Increased activity and proper breathing (diaphragmatic or abdominal breathing) increases respiratory efficiency, thus balancing pH.
[1] Revital Shurtz-Swirski, PHD, Shifra Sela, DSC, Avraham T. Herskovits, MD, Shaul M. Shasha, MD, Galina Shapiro, MSC, Lubna Nasser, MSC and Batya Kristal, MD. Involvement of Peripheral Polymorphonuclear Leukocytes in Oxidative Stress and Inflammation in Type 2 Diabetic Patients. Diabetes Care January 2001 vol. 24 no. 1 104-110
[2] Young IS, Tate S, Lightbody JH, McMaster D, Trimble ER: The effects of desferoxamine and ascorbate on oxidative stress in the streptozotocin diabetic rat. Free Radic Biol Med18 : 833-840,1995
[3] Ruiz C, Alegria A, Barbera R, Farre R, Lagarda MJ: Lipid peroxidation and antioxidant enzyme activities in patients with type 1 diabetes mellitus. Scand J Clin Lab Invest59 : 99-105,1999
[4] Ahonen TM, Saltevo JT, Kautiainen HJ, Kumpusalo EA, Vanhala MJ. The association of adiponectin and low-grade inflammation with the course of metabolic syndrome. Nutr Metab Cardiovasc Dis. 2010 Nov 17

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