Fat is more than an issue of appearance. Fat can lead to multiple chronic illnesses, and obesity is by far the greatest risk factor contributing to the burden of chronic diseases in the U.S. Obesity increases insulin resistance, blood pressure, LDL cholesterol, and triglycerides. Further, obesity lowers HDL cholesterol and places the body in a pro-inflammatory state.

Fat retention in the body is detrimental because fat cells networked together act as an endocrine organ. These endocrine secretions preserve and promote tumor progression, increasing the host’s consumption of nutrients. If you suddenly developed a large tumor in your right arm, you would likely pay attention to it. A tumor is merely a word that describes “swelling” and is further defined as “a swelling of a part of the body, generally without inflammation, caused by an abnormal growth of tissue, whether benign or malignant.” Think of fat as a tumor that is also an unregulated endocrine organ, and yourself as the host of this parasitic swelling.

Type 2 diabetes, with all of its excessive insulin levels, can also be thought of as signaling peptides promoting fat tumor production.

My point is not to create anorexics, but to have clinicians and patients recognize the significance of fat as more than an issue of appearance. Fat is metabolically active and is self-preserving.

About GGT (Oracle of Death or The final common Pathway) | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

Excess processed foods and carbohydrates can also lead to increased liver damage. GGT isn’t something that people consider when considering health risks, but it could be referred to as the “oracle of death” or “the final common pathway” because of how it predicts liver damage and subsequent disease. Gamma-glutamyl transferase (GGT) is an enzyme found in high concentrations in the liver, and it is elevated in diseases that cause damage to the liver.

GGT is a transferase that catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione (GSH) to an acceptor that may be any amino acid, a peptide, or water. GSH removes free radical toxins and provides natural protection against harmful oxidative stress. The normal biologic role of GGT is to reconstitute glutathione, the body’s master antioxidant.

GGT is the only enzyme of the GSH cycle located on the outer surface of the plasma membrane. It breaks down extracellular GSH and provides cysteine, the rate-limiting substrate, for intracellular de novo synthesis of GSH. When GGT concentrations are above “low-normal” ranges, excess GGT can catabolize (degrade) GSH, causing critical depletion of this antioxidant.

When GSH is depleted, oxidative stress and damage start to occur.  This leads to lead to a cycle of the irreversible cell, tissue, and DNA damage, and severe impairment of organ function. Elevated GGT indicates that you are demanding more GSH, and there was not enough GSH in the system to deal with an oxidative insult. During oxidative stress, GGT gene expression is increased, an adaptation to stress.

If you consume excess carbohydrates, processed foods, vegetable oil, alcohol, or other liver toxins, the liver can become insulin resistant, resulting in a high insulin level. Elevated insulin is a metabolic switch that causes fat to accumulate in the liver. Hyperinsulinemia (excess insulin) drives insulin resistance, and insulin resistance encourages more hyperinsulinemia.

As fat accumulates in the liver, the liver becomes more insulin resistant and simultaneously undergoes more oxidative stress, depleting Glutathione, which is reflected by increasing GGT.

 

GGT data was originally collected by the smartest guys in the room (life insurance actuaries), and the original reason for measuring it was its ability to mark alcohol abuse in life insurance applicants. The life insurance industry collected this data for many years, resulting in biometric stratification of mortality risk, and it has now become central to the life insurance underwriting process for predicting all causes of death.

Palmier J., Dixon A., Lanzarth B. Leading Contributors to Mortality Risk in Life Insurance Applicants. Schaumburg, Ill, USA: Society of Actuaries; 2012. (Smalltalk Issue 38).

Palmier J., Lanzrath B. J. Laboratory and biometric predictors of cancer-related mortality in an insured population. Journal of Insurance Medicine. 2012;43(3):162–168

 

Traditionally, elevated GGT has been associated with liver dysfunction, most often alcohol overconsumption. Other drugs that can elevate GGT include barbiturates, phenytoin, anti-inflammatory drugs (including aspirin), St. John’s Wort, and kava.

We now believe that elevated GGT is an early warning sign of other health risks, such as atherosclerosis, stroke, type 2 diabetes, kidney disease, cancer, metabolic syndrome (MetS), and all-cause mortality.

GGT doesn’t have to be above levels considered normal by a laboratory in order to have increased risks. When GGT concentrations exceed the lowest 25% to 35% of normal population ranges, disease risks grow in proportion to increased GGT. This “dose-response” increase in GGT concentration, indicates a greater risk of future diseases and mortality, even when GGT levels are within “normal” ranges.

Even a higher end of normal GGT poses a significant increase in risk:

Normal low

• < 9 U/l for women
• < 14 U/l for men

Moderately high with increased risk

• 18 U/I for women
• 28 U/I for men

High levels of normal with significant increase in risk

• >36 U/L for women
• >56 U/L for men

According to the National Institute of Health, “GGT levels measured in the Framingham Offspring Study (FOS), only moderately elevated GGT, starting at levels just above population GGT medians, and often measured one or two decades in advance of disease endpoints or mortalities, established GGT as an early predictive marker of MetS, CVD, heart failure, and all-cause mortality.”

 

Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk

Gerald Koenig, Stephanie Seneff. Dis Markers. 2015; 2015: 818570. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620378/

GGT is predictive of future mortality. In the general population, about 21% of men and 15.6% of women have elevated GGT. Elevated GGT, even within normal laboratory ranges, presents significant additional risks.

Patients with a high end of normal  GGT have more than a 1.5-fold risk of dying from cardiovascular diseases in comparison to people with normal low levels of GGT.

All-cause mortality and elevated GGT in the upper fifth of the population levels results in a 2x higher risk for all-cause mortality, 1.7x  higher risk for cardiovascular death, and 2.3x higher risk for cancer and death. Liver cancer and elevated GGT in the upper fifth of the population levels (not even top 1%) results in 15 to 18 times higher risk hepatic cancer and death from liver cancer

Hazard ratios

According to Clinical Chemistry, “GGT above the reference category (GGT ≥9 U/L in women, ≥14 U/L in men) was significantly (P <0.001) associated with all-cause, cancer, hepatobiliary, and vascular mortalities.”

Gamma Glutamyltransferase and Long-Term Survival: Is It Just the Liver? Lili Kazemi-Shirazi et al. DOI: 10.1373/clinchem.2006.081620 Published April 2007. http://clinchem.aaccjnls.org/content/53/5/940

Elevated levels also result in increased risk for atherogenic dyslipidemia, a predictor of impending heart disease. Dyslipidemia is a reflection of insulin resistance, and when your liver becomes insulin resistant, it will tend to cause visceral fat accumulation in your organs.  Visceral fat accumulation is most noticeably seen as a larger waist than expected, or a “beer belly,” even a small one in women.  Many people are apparently slim, but they are TOFI (thin outside, fat inside).

Dyslipidemia is a combination of high LDL, low HDL, high triglyceride, high particle count of LDL

• LDL:HDL
  Triglyceride:HDL
  LDL-P
  Oxidized LDL
  GGT

 

Most idiopathic or essential hypertension (where they don’t know the cause of the high blood pressure) – is related to hyperinsulinemia with resulting vessel stiffness and thickness.  Reversing hypertension may be as simple as reducing insulin.

GGT correlates with atherosclerotic plaque formation in arteries, which is associated with an inflammatory disease, metainflammation.

GGT activity also co- locates with oxidized LDL in the atherosclerotic plaque, as seen below.

Circulating Markers of Liver Function and Cardiovascular Disease Risk.

Arterioscler Thromb Vasc Biol. 2015 Nov;35(11):2290-6. doi: 10.1161/ATVBAHA.115.305235. Epub 2015 May 14.

https://www.ncbi.nlm.nih.gov/pubmed/25977566

Risk for future diabetes:

If your BMI is low and you have a low GGT, you have a baseline risk of 1.0

If you have a low BMI below 25 and a high GGT (in the top quarter of the population), you have a 3x risk of diabetes within 3-5 years

If you have a moderate-high BMI greater than 30 and a high GGT (in the top quarter of the population), you have a 15x risk of diabetes within 3-5 years

If you have a high BMI greater than 35 and a high GGT (in the top quarter of the population), you have a 19x risk of diabetes within 3-5 years

Obesity is one factor that predicts future diabetes, but GGT may be more accurate. If you correct the obesity level for GGT, obesity doesn’t predict diabetes. GGT is more predictive of diabetes as it reflects liver insulin resistance and liver inflammation.

Our treatment protocols for elevated GGT encourage:

• Decompress the fat out of the liver by either time-restricted feeding or fasting
• Eliminate vegetable oil and supplement with fish or krill omega-3 oil
• Switch to natural fats, such as butter and tallow
• Eliminate processed foods, including refined grains and acellular carbohydrates
• Metformin to enhance insulin sensitivity in the liver
• Moderate to high coffee consumption has been universally shown to reduce GGT

Time Restricted Feeding | Reverse Diabetes MD from Gurpreet Padda on Vimeo.

Time-restricted feeding.

Time-restricted feeding can help people move into a healthier lifestyle and reverse insulin resistance as well as maintain a healthy weight. Most people eat from the time they wake up until the time they go to bed; typically, they eat three main meals, multiple snacks, and often soda in between.  This pattern leads to chronic high insulin production, which fatigues the insulin receptors.  In addition, insulin is a fat storage hormone, and elevated insulin levels lead to fat accumulation in the liver, creating metabolic inflammation.

Your metabolism exists in two states – the “fed” (insulin high) state and the “fasted” (insulin low) state. Either we are storing food energy (increasing storage), or we are burning stored energy (decreasing storage or fat lysis).  If we start eating the minute we roll out of bed and do not stop until we go to sleep, we spend almost all our time in the fed state. Over time, we gain weight, because we have not allowed our body time to burn stored food energy.

Time-restricted feeding shortens the time window that a patient eats, shortening the “fed” state and lengthening the “fasted” state.  This reduces the total amount of insulin produced for the day.  Insulin is a fat-storage hormone, and a high level of insulin production leads to insulin resistance.  Time-restricted feeding is considered a type of fasting and has extraordinary benefits, including weight and body fat loss, lowered blood insulin and sugar levels, and a reversal of type 2 diabetes. Other possible benefits include improved mental clarity and concentration, a reduction in the risk of Alzheimer’s disease, activating of cellular cleansing by stimulating autophagy, and reduction of inflammation.

Time-restricted feeding is a type of fasting; it is not starvation.  Starvation is the involuntary absence of food for a long time, leading to severe suffering or even death. Starvation is not deliberate or controlled.  Fasting is the voluntary withholding of food. It’s done by someone who is not underweight and thus has enough stored body fat to live off. When done right, intermittent fasting should not cause suffering.  Food is easily available, but you choose not to eat it. You may begin a fast at any time of your choosing, and you may end a fast at will, too. You can start or stop a fast for any reason or no reason at all.  Any time that you are not eating, you are intermittently fasting. For example, you may fast between dinner and breakfast the next day, a period of approximately 12-14 hours. In that sense, intermittent fasting should be considered a part of everyday life.

The mere presence of insulin increases fat storage, and the absence of insulin permits lipolysis or fat usage as energy.

Lifestyle changes are key to managing obesity and Type 2 Diabetes, but by themselves don’t always control blood glucose levels. Bariatric surgery (gastric band or bypass) is effective but has significant risk. Drugs often manage the symptoms and may stave off complications, but don’t reverse the disease.

Time-restricted feeding has the potential to fill this gap in obesity and diabetes care by providing calorie restriction and the hormonal benefits of bariatric surgery without invasive surgery. Time-restricted feeding is defined as the controlled and voluntary abstinence from all calorie-containing food and drinks for a specified period of time.  During the fasting periods, patients are allowed to drink unlimited amounts of very-low-calorie fluids such as water, coffee, tea, and even bone broth. A general multivitamin supplement is encouraged to provide adequate micronutrients.

Metabolic flexibility:

Time-restricted feeding, or meal-timing strategy, reduces swings in hunger and alters fat and carbohydrate burning patterns, which may help with losing weight and improving insulin sensitivity.  It does not necessarily affect how many total calories patients burn but reduces the daily hunger swings and increases fat burning at night. It improves metabolic flexibility, which is the body’s ability to switch between burning carbs and burning fats.  Metabolic flexibility is the ease with which the body transitions between two different and opposing states, “fed” and “fasted,” without cravings or hunger pangs.

During feeding, insulin is elevated, which signals your body to store excess calories as fat. In the presence of insulin, the burning of fat is halted, while the body burns glucose instead.  In the fasted state, insulin is low (while glucagon and growth hormone increase), so the body mobilizes stored body fat from your fat cells and burns this fat for energy (instead of glucose).  You can only burn stored body fat while in the fasted state, and you can only store more body fat while in the fed state.

Most overweight patients live in a constant fed state, and rarely in a fasted state.  They continually burn glucose rather than fat at the cellular level. They have insulin resistance, caused by chronically high insulin levels, which promote fat storage and suppress fat mobilization.

When overweight “sugar burners” stops eating for even a few hours, they quickly run out of glucose from their last meal, instead of transitioning to the fasted state and burning stored body fat.  This causes acute brain signals of hunger and cravings for immediate sugar.  They spend most of the day trapped in a cycle of eating every few hours, spiking glucose, and then becoming hungry when blood sugar drops.  They may even develop low blood sugar and feel jittery; this is called reactive hypoglycemia.  This is a big clue that a patient lacks metabolic flexibility.

Fat-adapted energy use:

Your metabolic flexibility is determined by your mitochondria, the tiny energy factories inside the cells.  The mitochondria can burn both glucose (sugar) or fat for fuel, and over time they will develop a preference for one over the other; “sugar burners” have increased the pathways in the mitochondria that burn glucose and decreased pathways for burning fat.  As you become more metabolically flexible, the fat burning pathways will predominate, and you will become “fat adapted.”

Becoming fat adapted takes time and practice, and your body has to do a number of things to slowly up-regulate (or increase) your fat-burning pathways.  This includes improving insulin sensitivity to lower insulin and promote fat mobilization into free fatty acids and upregulating the fat-burning pathways at the cellular level (in the mitochondria).

Ways to improve fat adaptation include:

• Low-carbohydrate diets: A low-carb, high-fat (LCHF) diet improves the body’s ability to utilize fat for energy rather than glucose, as there is more fat and less glucose, even in the fed state.
• Exercise: High-intensity exercise depletes glucose and glycogen rapidly, forcing the body to switch to fat for fuel. Exercise also improves insulin sensitivity.
• Caloric restriction: Eating fewer calories also equals less glucose available for fuel, forcing the body to rely on stored body fat for fuel.
• Intermittent fasting forces the body to spend more time in the fasted state, giving the body more “practice” at burning fat.
• Supplementation: Ketone supplementation may be useful when first starting out. Ketones are breakdown products of fat, and when you first start out, ketones can reduce your hunger and provide energy for your mitochondria.

Patient education and engagement is the key to remission and curtailing the use of pharmacological interventions.  Morrison et al, also found that more frequent interactions with a provider led to markedly rapid reductions in serum glucose, HbA1C, and low-density lipoprotein cholesterol levels, followed up with the treating physician on average every 2 weeks.

How to do time-restricted feeding:

Our protocol can reverse obesity and Type 2 Diabetes (in individuals who still have the capacity to produce some insulin) by resensitizing the insulin receptor and restoring normal cyclical insulin production.  We restore the normal ebb and flow pattern of insulin, so the receptors are re-sensitized, and the constant high level of circulating insulin is reduced, reducing the fat storage action of insulin.

Time-restricted feeding is a type of intermittent fasting that limits your food intake to a certain number of hours each day.  An example of time-restricted eating is if you choose to eat all your food for the day in an 8-hour period, such as from 11 a.m. to 7 p.m., providing an 8-hour feeding window.  The remaining 16 hours are the fasting period, during which no calories are consumed.  This same schedule would be repeated every day.

Restricting feed times to a shorter window each day, starting at 8 hours/day and reducing by 1 hour per week down to 4-6 hours/day is highly effective in reversing diabetes and weight loss.  Medications must be clinically adjusted to prevent unintentionally low glucose levels or changes in blood pressure, which can be life-threatening.  To have success with this technique, cravings should be prevented.  Satiety is the key; you should not be hungry, or this will not be sustainable.  Food choice drives satiety.

Steps to success

Step 1

Before you start a time-restricted feeding schedule, you should talk to your doctor or health care provider. Get medical advice from a professional who is aligned with your health goals.

You may have medical conditions that need close monitoring. Likewise, you may be on medications that may need to be adjusted. It is important to have a strong understanding of your medical history and the medications you take prior to initiating a fasting program. Please talk to your doctor or healthcare provider.

Step 2

Stop all sugars, including all artificial sweeteners. Many sugars and processed carbs just aren’t satiating. Stop all sugar and artificial sugar sweetened beverages. Before you start your protocol, you should eliminate sugars and processed carbohydrates.

Stop all sources of vegetable oil and replace with healthy natural oil and real butter.  Replacing industrial seed oil with real oils is easy if you are not eating processed foods.  It even makes the food taste better.

Stop all processed foods.  Processed foods are engineered to make you eat again and again and again, every 2-3 hours.

Step 3

Focus on protein and healthy fats. Focus on getting meals that are rich in protein and healthy fats. Eat all types of meat like beef, fish, chicken, eggs, lamb, and seafood. Yogurt and cheeses are also nutritious and filling. Fill up on low-sugar vegetables like olives, peppers, cucumbers, and avocado, and eat as many green leafy vegetables as you please.  This approach will help you get better adapted to fat metabolism and may make fasting easier to adopt.

Step 4

Start slow.   This metainflammation didn’t happen in one day, and it won’t go away in a day. Consider a liberal 8-hour eating window on your first day to see how it feels. Eat as you please during your 8-hour time frame and see how your body and appetite feel during the remaining hours of the day.

Then, slowly narrow your eating window. As you feel more comfortable assessing your hunger and understanding the nature of hunger pangs, you can slowly decrease your daily feeding window. Consider decreasing by one hour a week, until you reach a 4-hour window.

Things to think about:

If you haven’t made adjustments to your diet beforehand to include more satiating foods filled with protein, healthy fat and fiber, you may notice hunger pangs. If you are experiencing hunger pangs, consider drinking some hot tea, coffee, water or seltzer. This will fill your stomach up and give you enough time to realize that maybe you really aren’t as hungry as you initially thought.  Some people use lemon in seltzer water.

This should be a fun experience, not a miserable experience.  If you are having a miserable experience, something has been overlooked.  Remember that time-restricted feeding is a  great way to limit snacking. Eating satiating real food during your eating window will restore and realign your hormone system.

Patients can reverse their diseases without the worry of side effects and financial burden of many pharmaceuticals, as well as the unknown long-term risks and uncertainty of surgery, all by means of time-restricted feeding.

Some practical tips:

• Don’t use time restricted feeding as an excuse to eat junk food when you are eating—continue to avoid processed foods.
• When you first start time-restricted feeding, you might have to supplement with a fast-mimicking substance like a ketone supplement.
• Check with your doctor before starting time-restricted feeding, especially if you are diabetic and on diabetes medications!
• You can generally take any vitamins or supplements you want while fasting as long as they don’t have calories, but you don’t need any supplements as you will be eating plenty of nutrient-dense foods every day. You may have to increase salt intake.
• You don’t have to worry about losing muscle from lack of protein during your fast, as long as you eat adequate protein at the meals before and after fasting. A LCHF (low-carb, high-fat) diet pairs nicely with intermittent fasting, as both improve fat adaptation a great deal.
• Exercising with time restricted feeding, either cardio or lifting weights (lifting weights is better), is acceptable. You will not lose muscle while fasting as long as you are exercising regularly.
• Drink plenty of water and non-caloric beverages while fasting; coffee and tea in the morning make fasting considerably more enjoyable in addition to health and fat-burning benefits and are highly recommended. You may have to increase salt intake.
• Skipping your morning meal gives your body more time to burn fat for energy. Hunger is lowest in the morning, so it may be easiest to skip it and break your fast later in the day.

Time-restricted feeding has many benefits but remains controversial. Diabetes medications will need to be adjusted. Discuss any changes in medication and relevant lifestyle changes with your doctor.  People who should not use time-restricted feeding include those who are underweight or have eating disorders, pregnant or breastfeeding women, and children under the age of 18.

Need more help? We have more to offer.

Additional references:

Suleiman Furmli, Rami Elmasry, Megan Ramos, Jason Fung. Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin. BMJ Case Reports, 2018; bcr-2017-221854 DOI: 10.1136/bcr-2017-221854

Morrison F , Shubina M , Turchin A . Encounter frequency and serum glucose level, blood pressure, and cholesterol level control in patients with diabetes mellitus. Arch Intern Med 2011;171:1542–50.doi:10.1001/archinternmed.2011.400

Duke S-AS , Colagiuri S , Colagiuri R . Cochrane Metabolic and Endocrine Disorders Group. Individual patient education for people with type 2 diabetes mellitus. Cochrane Database Syst Rev 2009;22.doi:10.1002/14651858.CD005268.pub2

Brethauer SA , Aminian A , Romero-Talamás H , et al . Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg 2013;258:1.doi:10.1097/SLA.0b013e3182a5034b

Pucher PH , Lord AC , Sodergren MH , et al . Reversal to normal anatomy after failed gastric bypass: systematic review of indications, techniques, and outcomes. Surg Obes Relat Dis 2016;12:1351–6.doi:10.1016/j.soard.2016.01.030

Shoar S , Nguyen T , Ona MA , et al . Roux-en-Y gastric bypass reversal: a systematic review. Surg Obes Relat Dis 2016;12:1366–72.doi:10.1016/j.soard.2016.02.023

The University of Alabama at Birmingham. “Time-restricted feeding study shows promise in helping people shed body fat.” ScienceDaily. ScienceDaily, 6 January 2017. www.sciencedaily.com/releases/2017/01/170106113820.htm

Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? K. A. Varady. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2011.00873.x

Moro, T., Tinsley, G., Bianco, A., Marcolin, G., Pacelli, Q. F., Battaglia, G., … Paoli, A. (2016). Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. Journal of translational medicine, 14(1), 290. doi:10.1186/s12967-016-1044-0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064803/

Gabel, K., Hoddy, K. K., Haggerty, N., Song, J., Kroeger, C. M., Trepanowski, J. F., … Varady, K. A. (2018). Effects of 8-hour time restricted feeding on body weight and metabolic disease risk factors in obese adults: A pilot study. Nutrition and healthy aging, 4(4), 345–353. doi:10.3233/NHA-170036. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004924/