Can You Benefit From A Fast, Flexible Keto Diet?

Can You Benefit From A Fast, Flexible Keto Diet?

Part Two of the Keto on Demand Blog, go here for Part 1

There’s hardly a diet on the planet that doesn’t tempt one to cheat sometimes—whether at home alone, a party, a business lunch, on vacation, or just whenever the overwhelming urge to eat something delicious and forbidden strikes. The ketogenic diet is no exception. This high fat, low protein, and very low-carb diet offers amazing benefits—from weight loss, to sustained energy, and improvements in cognition, mood, neurological function, exercise performance, cholesterol, blood sugar levels and more—but can be tough to follow all the time.

So the question du jour is, can you gain the benefits of keto and still “cheat”? Is there such a thing as flexible ketosis? What would it look like, and would you still benefit?

As we explained in Part One of this blog, a keto diet triggers your body’s ancient ability to go into a metabolic state called ketosis. In ketosis the body becomes superbly efficient at burning fat for energy, in the form of ketones. Ketones are a particularly rich energy source for our energy-hungry brains, and they create fewer damaging reactive oxygen species and free radicals. Some scientists now call ketones the fourth energy source for humans (in addition to carbohydrates, fats and proteins.)

In ketosis, your mitochondria function better, new mitochondria are created at a faster rate, glutathione production is increased, and metabolism becomes more efficient. The ketogenic diet is also likely linked to longer lifespan and a lower risk of age-related diseases.[1]

Yet most Americans today overindulge in carbohydrates. In fact, many of us are eating a diet of 55-65 percent carbohydrates, in part based on USDA guidelines. Not surprisingly, all those carbs put on weight, and early 40 percent of American adults, over 18 percent of teens and nearly 14 percent of young children are now obese.[2]

The keto diet turns the standard American diet on its head. A ketogenic diet slashes carbs to about 25 grams a day (as opposed to the American average of 275 carbs a day). It’s easy to slip over that allotment. And the accepted wisdom is that while it can take up to six weeks to become fully fat-adapted in ketosis, you only need one brief binge, one carb-heavy meal or day of indulgence to slip out of it. In fact, in an interview with Men’s Health Magazine, Ginger Hultin, MS, RDN, CSO, Seattle-based dietitian and Spokesperson for the Academy of Nutrition and Dietetics, said that even one wrong drink or bite could push you out of ketosis: “Juice, soda, candy will meet that [carb] limit in small amounts.” Hultin says that “as soon as you introduce carbohydrates to your system, the body will use them preferentially for fuel.”

According to Hultin, it may take a few days to get back into ketosis after cheating, and you may even experience “keto flu” symptoms, such headaches, nausea, fatigue, aches, brain fog, and moodiness.

But is that really the case? Read on to find out how you can quickly move into ketosis and fat-burning and even follow an intermittent ketogenic diet, achieving the benefits of keto with a less restrictive and more balanced food plan. First, you need to know a bit about the pathways that a ketogenic diet activates; and then how to support those same pathways with specific botanicals.

Why “Eating Yourself” Is Important: The Health-Boosting Process of Autophagy

All complex life on earth depends on certain universal and ancient pathways. These deep and ancient signaling pathways and receptors evolved in a time when food was not available 24/7 and when a sedentary lifestyle was not common. We frequently moved from fed to fasted and back to fed, from intense activity to rest and back to bursts of activity. During times of fasting or food scarcity, when we had no food to digest, our bodies cleaned themselves—digesting, recycling and disposing of wastes, toxins, debris, and damaged cells. This is called “autophagy” and literally means “to eat oneself” (from the Greek auto and phagein).[3] Autophagy helps keep us healthy, and it helps us fight and digest pathogens as well. Malfunctions in autophagy are linked to many human diseases, including cancers and neurodegeneration.[4]. Autophagy is so important and fundamental that in 2016, the Nobel Prize in Physiology or Medicine was awarded to scientist Yoshinori Ohsumi for his discoveries about autophagy.[5]

Autophagy works in harmony with multiple pathways. One of the most important is called AMP activated protein kinase or AMPK.[6] Here’s what you need to know about AMPK: it is a central regulator of metabolism, growth and energy.[7] It is activated whenever intracellular energy is low.[8]  AMPK activation restores energy by stimulating many important pathways and processes.[9] AMPK may help stimulate weight loss, improve insulin sensitivity, decrease inflammation, and enhance muscle performance and contraction.[10],[11] AMPK is also associated with healthy aging.[12]

AMPK is activated by calorie and carbohydrate restriction, lowered blood insulin levels, and muscle contraction during exercise.[13] AMPK is inhibited by chronic overnutrition, excess insulin and obesity.[14],[15] AMPK helps regulate other profoundly important pathways in your body that modulate carbohydrate and fat metabolism and stimulate the formation of new mitochondria (called mitochondrial biogenesis).[16],[17]  These include pathways with names such as mTOR, PPAR, PCG1 and more. These complex pathways harmonize like an orchestra, carefully regulating metabolism and health.

Activation of AMPK is something we can directly affect through our lifestyle, diet and exercise. And it puts us in an enhanced metabolic state to fight disease.[18] A Keto diet jumpstarts autophagy, and increases AMPK activity. This becomes more important as we age, and the ability to eliminate damaged proteins declines.[19]

Unique Botanicals Can Support Ancient Pathways In The Way That Keto Diets Do

Billions of years ago—or so the story goes—two bacteria bobbing in the ocean encountered each other. Somehow, one engulfed the other, and both survived. Over time, the one that got eaten evolved into the small but powerful mitochondria. That probably took a few million years. The other bacteria probably evolved into the nucleus of the cell. And this was the beginning of complex life on the planet. Mitochondria dedicated themselves to producing energy. They were so spectacular at this that a rich variety of life forms soon spread across the planet. Energy was the currency of spectacular complexity.

Meanwhile, something very similar was happening in the plant world. Bacteria called cyanobacteria (think of blue-green algae today) could generate energy directly from the photons of the sun. At some point they merged with other bacteria, and this led to the entire kingdom of plants. Over time, cyanobacteria evolved into chloroplasts, and like mitochondria, they now generate energy for the cell, directly from the sun.[20] Plants, too, need to both create energy and to clean up their own waste products. Plants also activate autophagy through AMPK and other signaling pathways much like ours.[21]

It’s not surprising, then, that certain specialized botanicals may be able to complement our own signaling pathways and support autophagy, and the very same metabolic features that a keto diet supports. Here is a short list of a few potent botanicals that activate AMPK, autophagy, and the kind of cleansing and repair mechanisms that extend life and support health.

Resveratrol found most commonly in grapes—is well known for research on its antioxidant power and ability to extend lifespan. Harvard Medical School geneticist David Sinclair, has found that resveratrol extends lifespan by mimicking caloric restriction and inducing autophagy, in some cases in as little as four to six hours.[22] It stimulates AMPK[23] and induces autophagy by targeting a complex array of autophagy-associated proteins.[24],[25] Resveratrol enhances thermogenesis and increases the growth of new mitochondria.[26]

Milk Thistle This widely used liver-supportive botanical turns out to contain a potent flavonoid, silibinin, that induces autophagy. Silibinin can induce autophagy, in part through AMPK signaling.[27] Silibinin activates AMPK, and can restore NAD+ levels in non-alcoholic fatty liver.[28]

Quercetin is a potent flavonoid that is widely used for its antioxidant and anti-inflammatory ability. Quercetin activates AMPK, and activates autophagy.[29] ,[30],[31],[32] ,[33]  Quercetin increases the growth of new mitochondria, reduces inflammation, and offers anti-inflammatory, antihistamine and immune support.[34],[35],[36]

Berberine (found in botanicals such as goldenseal and Oregon grape root) has the ability to modulate autophagy and help prevent obesity and metabolic syndrome.[37],[38],[39] Berberine activates AMPK[40] and increases the growth of new mitochondria.[41]

Diindolylmethane (DIM) is a dietary supplement derived from cruciferous vegetables such as broccoli, brussel sprouts, cabbage and cauliflower. DIM has been extensively studied for its ability to modulate estrogen dominance. DIM activates autophagy, in part by activating AMPK.[42] DIM is immune stimulating and immune balancing, shifting the balance towards a calmer immune response.[43],[44]

Cinnamon contains a key bioactive compound, trans-cinnamic aldehyde, which decreases bacterial survival by activating autophagy in microbial invaders.[45] Cinnamon activates AMPK.[46],[47]

Flexible Ketosis: The Ultimate Win-Win Strategy?

Like all complex life on this planet, we alternate between bursts of activity and times of recovery, and between feeding and fasting. During our times “offline”, we engage in rest and repair. Almost every aspect of our physiology reflects this movement between two states of activity and rest. In fact, abundant research suggests that we do best when we regularly move between the two.[48]

 Phytonutrients can activate the same pathways induced by a ketogenic diet, and by so doing, can support ketosis even if we consciously slip out of it. There is an abundance of evidence now that chronic “overnutrition” is not what evolution intended. We evolved to thrive through periods of feast and famine, plenty and scarcity, high demand as well as times of rest and regeneration.[49]  Like keto, the ingredients in botanicals can help us rebuild, repair, and regenerate from the cellular level on up.[50] 

A flexible keto diet allows for periods of carbohydrate “fasting” and periods of carbohydrate “feasting”. By adding complex carbohydrates back into our diet for short bursts of time, we can feed our liver, which depends on glucose. We can feed our food cravings–who doesn’t want freshly baked whole grain bread, still warm from the oven? Who doesn’t want the occasional pasta drenched in marinara sauce and drizzled with cheese? How about polenta, kasha, quinoa, oatmeal with milk and honey? We can feed a diverse gut microbiome—for many of our friendly probiotic bacteria feast on the starches in grains and beans, or the sugars in dairy. These carbs function as prebiotics, that help our friendly flora modify the mucosal lining of our gut and keep it healthy.[51]

Intermittent keto, or keto-on-demand, is a novel approach to health and wellness. With botanical support, one may follow a ketogenic diet before dinnertime, and then ‘break the fast’ with a nutrient-rich, complex carbohydrate-rich meal in the evening. Keto-induced pathways will be supported by botanical assistance during this brief but delicious diversion.

Though many nutraceuticals can support us as we move into fat-burning and nutritional ketosis, a liposomal nanoemulsion will deliver these nutrients more rapidly. In addition to exceptional absorption rates, liposomes enhance lymphatic circulation of nutrients and support cellular delivery. The phosphatidylcholine in high-quality liposomes also supports the energy-rich, fat-reliant metabolism of ketosis.

You May Also Be Interested In:

Can You Reap the Rewards of Keto Without the Downsides?

Humble but Powerful: Cruciferous Vegetables Detoxify via a Potent Molecule called DIM

Are You Ready for a New You?

[1]Moreno CL, Mobbs CV. Epigenetic mechanisms underlying lifespan and age-related effects of dietary restriction and the ketogenic diet. Molecular and cellular endocrinology, 2017;455, 33-40.

[2]Hales CM, Fryar CD. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA. 2018 Apr 24;319(16):1723-1725

[3]Seglen PS, Bohley P.  Autophagy and other vacuolar protein degradation mechanisms. Experientia, 1992;48(2), 158-172

[4]Huang J, Klionsky DJ. Autophagy and human disease. Cell Cycle. 2007;6:1837–1849. 

[5]Levine B, Klionsky DJ. Autophagy wins the 2016 Nobel Prize in Physiology or Medicine: Breakthroughs in baker’s yeast fuel advances in biomedical research. Proceedings of the National Academy of Sciences, 2017;114(2), 201-205

[6]Kim J, Kundu M. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011 Feb;13(2):132-41

[7]Kahn BB, Alquier T et al. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005; 1:15–25.

[8]Bland ML, Birnbaum MJ Cell biology. ADaPting to energetic stress. Science. 2011 Jun 17;332(6036):1387-8

[9]Ruderman NB, Xu XJ et al. AMPK and SIRT1: a long-standing partnership?. Am J Physiol Endocrinol Metab. 2010;298(4):E751–E760

[10]Ruderman NB, Xu XJ et al. AMPK and SIRT1: a long-standing partnership? Am J Physiol Endocrinol Metab 2010; 298: E751–E760

[11]Sahlin K, Tonkonogi M et al. Energy supply and muscle fatigue in humans. Acta Physiol Scand 1998; 162: 261–266.

[12]Salminen A, Kaarniranta K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 2012; 11: 230–241.

[13]Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245

[14]Coughlan KA, Balon TW et al. Nutrient excess and AMPK downregulation in incubated skeletal muscle and muscle of glucose infused rats. PLoS ONE 2015; 10: e0127388

[15]Valentine RJ, Coughlan KA et al. Insulin inhibits AMPK activity and phosphorylates AMPK Ser(4)(8)(5)/(4)(9)(1) through Akt in hepatocytes, myotubes and incubated rat skeletal muscle. Arch Biochem Biophys 2014; 562: 62–6

[16]Wu Z, Puigserver P et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98:115–124

[17]Koh JH, PPARβ Is Essential for Maintaining Normal Levels of PGC-1α and Mitochondria and for the Increase in Muscle Mitochondria Induced by Exercise Hancock CR et al. Cell Metab. 2017 May 2;25(5):1176-1185.e5. doi: 10.1016/j.cmet.2017.04.029

[18]Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer. 2009;9(8):563-575

[19]Bordi M, Berg MJ et al. Autophagy flux in CA1 neurons of Alzheimer hippocampus: increased induction

overburdens failing lysosomes to propel neuritic dystrophy. Autophagy 2016; 12 (12), 2467–2483.

[20]Mereschkowsky C. Über Natur und Ursprung der Chromatophoren im Pflanzenreiche. Biol Centralbl. 1905;25:593–604.

[21]Rensburg HC, Ende, W. Autophagy in plants: both a puppet and a puppet master of sugars. Front Plant Sci. 2019 Jan 22;10:14

[22]Armour, SM, Baur JA et al. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging (Albany NY), 2009;1(6), 515.

[23]Zang M, Xu S et al. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes. 2006 Aug;55(8):2180-91.

[24]Armour SM, Baur JA et al. Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy. Aging (Albany NY). 2009;1(6):515-28

[25]Opipari AW Jr, Tan L et al. Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res 2004; 64: 696–703.

[26]Baur JA, Pearson KJ et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16; 444(7117):337-42

[27]Liu X, Xu Q et al. Silibinin-induced autophagy mediated by PPARα-sirt1-AMPK pathway participated in the regulation of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes. Mol Cell Biochem. 2019 Jan;450(1-2):1-23

[28]Salomone F, Barbagallo I et al. Silibinin Restores NAD⁺ Levels and Induces the SIRT1/AMPK Pathway in Non-Alcoholic Fatty Liver. Nutrients. 2017 Sep 30;9(10

[29]FEng K, Chen Z et al. Quercetin attenuates oxidative stress-induced apoptosis via SIRT1/AMPK-mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model J Cell Physiol. 2019 Mar 10.[Epub ahead of print]

[30]Kim SG, Kim JR et al. Quercetin-Induced AMP-Activated protein kinase activation attenuates vasoconstriction through LKB1-AMPK signaling pathway. J Med Food. 2018 Feb;21(2):146-153.

[31]Klappan AK, Hones S. Proteasome inhibition by quercetin triggers macroautophagy and blocks mTOR activity Histochem Cell Biol. 2012 Jan;137(1):25-36

[32]Wang K, Liu R et al. Quercetin induces protective autophagy in gastric cancer cells: involvement of Akt-mTOR- and hypoxia-induced factor 1alpha mediated signaling. Autophagy 2011: 7, 966–978.

[33]Klappan AK, Hones S. Proteasome inhibition by quercetin triggers macroautophagy and blocks mTOR activity. Histochemistry and Cell Biology 2012; 137, 25–36.

[34]Escande E, Nin V et al. Flavonoid apigenin Is an inhibitor of the NAD+ ase CD38 implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes, 20113; 62(4), 1084-1093.

[35]Li X, Wang H et al. Protective effects of quercetin on mitochondrial biogenesis in experimental traumatic brain injury via the Nrf2 signaling pathway. PLoS One. 2016 Oct 25;11(10):e0164237

[36]Shaik Y, Caraffa A. Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin. Cent Eur J Immunol. 2018;43(4):476-481

[37]Deng Y, Xu J. et al. Berberine attenuates autophagy in adipocytes by targeting BECN1. Autophagy, 2012; 10(10), 1776–1786

[38]Fan A, Wang J. Berberine alleviates ox‐LDL induced inflammatory factors by up‐regulation of autophagy via AMPK/mTOR signaling pathway. Journal of Translational Medicine, 2015; 13(1), 92.

[39]Yao Z, Wan Y. Berberine induces mitochondrialmediated apoptosis and protective autophagy in human malignant pleural mesothelioma NCIH2452 cells. Oncol Rep. 2018 Dec;40(6):3603-3610

[40]Choi Y, Lee K et al. Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice. Toxicol Appl Pharmacol. 2017 Feb 1;316:74-82

[41]Gomes AP, Duarte FV et al. Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis. Biochim Biophys Acta. 2012 Feb;1822(2):185-95

[42]Draz H, Goldberg AA et al. Diindolylmethane and its halogenated derivatives induce protective autophagy in human prostate cancer cells via induction of the oncogenic protein AEG-1 and activation of AMP-activated protein kinase (AMPK). Cell Signal. 2017 Dec;40:172-182

[43]Lui Y, She W et al. 3, 3′-Diindolylmethane alleviates steatosis and the progression of NASH partly through shifting the imbalance of Treg/Th17 cells to Treg dominance. Int Immunopharmacol. 2014 Dec;23(2):489-98

[44]Xue L, Pestka J et al. 3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo. J Nutr Biochem. 2008 May;19(5):336-44

[45]Chung J, Kim S et al. Trans-cinnamic aldehyde inhibits Aggregatibacter actinomycetemcomitans-induced inflammation in THP-1-derived macrophages via autophagy activation J Periodontol. 2018 Oct;89(10):1262-1271

[46]Shen Y, Honma N et al. Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling. PLoS One. 2014 Feb 14;9(2):e8789

[47]Kopp C, Singh SP. Trans-cinnamic acid increases adiponectin and the phosphorylation of AMP-activated protein kinase through G-protein-coupled receptor signaling in 3T3-L1 adipocytes. Int J Mol Sci. 2014 Feb 19;15(2):2906-15

[48]Cronise RJ, Sinclair DA et al. The “metabolic winter” hypothesis: a cause of the current epidemics of obesity and cardiometabolic disease. Metab Syndr Relat Disord. 2014;12(7):355-61.

[49]Guarente L. Mitochondria—a nexus for aging, calorie restriction, and sirtuins? Cell 2008;132:171–176

[50]Condello M, Pellegrini E, Caraglia M, Meschini S. Targeting Autophagy to Overcome Human Diseases. Int J Mol Sci. 2019;20(3):725

[51]Langlands SJ, Hopkins MJ et al. Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel. Gut. 2004;53(11):1610–1616