Almost two years ago, this magazine ran an article entitled

"Supplements Target Ketogenesis and Metabolic Flexibility for Sports and Health."1 (June 2016) Last month there was a review of the state of caloric restriction / fasting and ketogenic diets today. However, many readers have little interest in either caloric restriction or ketogenic diets as lifestyle choices. Both of these approaches are difficult to follow even if being utilized for specific health purposes. Nevertheless, their basic principles have application to general health and to athletics. The foremost impediment to taking advantage of these approaches was laid out in the 2016 article.

A major problem in achieving keto-adaptation by diet alone is that most individuals who have been raised on Western-style diets can take six months or more to make the shift and this shift becomes ever more difficult as we age. Studies examining the role of carbohydrates in the metabolism with roughly 30 year old males in good physical condition have revealed, for instance, that even transitioning from a high glycemic index diet to a low glycemic index diet while maintaining the same ratio of carbohydrate, fat and protein can take more than four weeks. Shifting to fatty acid metabolism for energy can be difficult.

For most of us, the issue is whether a moderate change in diet accompanied by a judicious utilization of special foods and dietary supplements can achieve the goals usually associated with caloric restriction, fasting and ketogenic diets. Fortunately, the answer for the preponderance of readers is "yes." Both for anti-aging purposes and for athletics, metabolic flexibility likely can be achieved through approaches within the reach of almost everyone. The goal is not to be ketogenic all the time, but to be able to metabolize ketones and free fatty acids routinely and easily. For a nice introduction to the distinction, readers might visit the blog entitled "Ketogenesis, Measuring Ketones, and Burning Fat vs Being in Ketosis."2

The Diet

Previously in these pages, it was noted that consuming too little protein presents issues, but, likewise, too much protein in the diet, meaning above roughly 30 percent of calories, defeats a major goal of caloric restriction, which is to not just reduce circulating insulin, but also to avoid elevating insulin-like growth factor-1 (IGF-1). Although those not trained in nutrition seldom realize this, protein sources can be used for gluconeogenesis, which is to say, to produce glucose from, non-carbohydrate sources. It is not just consuming too little fat and too much carbohydrate or too much of these two together with too little protein that defeat the aims of an anti-aging diet.

The recent Prospective Urban Rural Epidemiology (PURE) study followed 135,335 adults in eighteen countries for over seven years with respect to morbidity and mortality in terms of cardiovascular disease, strokes and non-cardiovascular disease mortality as correlated with the effects of nutrients.3 In an interview, Dr. Mashid Dehghan, the lead author, reported that Participants were categorized into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality.

As noted by the researchers, their results flatly contradict decades of nutritional advice: High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.

In the PURE study, those who consumed at least 35 percent of their calories from fat were 23 percent less likely to die than those who consumed only 10 percent or less as fat. According to PURE findings, the higher the fat intake, the less the chance of stroke. Those who consumed 77 percent of their calories as carbohydrates were 28 percent more likely to die than those who consumed less than 46 percent as carbohydrates. The conclusion of the study? "In a nutshell, a healthy diet based on the PURE results would be rich in fruits, beans, seeds, vegetables, and fats, include dollops of whole grains, and be low in refined carbohydrates and sugars."

The observant reader who takes the time to look at the PURE study's findings will quickly realize that the traditional reliance on "markers" such as blood LDL-cholesterol levels—markers long used to argue against the inclusion saturated fats any large amount of fats in general in the diet as well to promote carbohydrate consumption— does not correspond well with the actual endpoints of morbidity and mortality. This does not mean that the PURE diet needs to be ketogenic. To quote from the TotalHealth 2016 article, As admitted by Ben Greenfield, a serious triathlete who was tested with regard to the ergogenic benefits of a ketogenic diet, "after the study at University of Connecticut, I personally quit messing around with ketosis and returned to what I considered to be a more sane macronutrient intake of 50-60% fat, 20- 30% protein, 10-30% carbohydrate."4

As a practical matter, a more normal diet with supplements might look like this:
The diet should not be high in simple sugars, fructose or refined carbohydrates. For non-athletes and those looking primarily to increase metabolic flexibility, the diet should resemble a modified Sears Diet, meaning approximately 20 - 30 percent protein, 30 - 40 percent carbohydrate and 30 - 40 percent fat. For athletes and individuals who seriously want to initiate and maintain a fat-adapted diet, Ben Greenfield's suggestion is more in order: "50-60% fat, 20-30% protein, 10-30% carbohydrate."

Those who want to achieve most of the benefits of a ketogenic diet without undergoing the grueling restrictions normally involved (limitations not just on carbohydrate intake, which are extreme, but also on protein intake) should consider the fact that ketone bodies supply 2–6 percent of the body's energy requirements after an overnight fast (no eating at bedtime) with the higher figure reflecting a longer period without eating. After three days of fasting, 30–40 percent of energy needs are met by endogenously produced ketones. Such facts, again, lead to at least two possibilities aside from caloric restricted and ketogenic diets. First, will consuming exogenous ketones as esters or salts provide the same benefits as special diets? Second, is there a role for dietary supplements in delivering these benefits?

Ketones (Acetoacetate and β-hydroxybutyrate) Esters and Salts?

The new kid on the block in anti-aging and sports supplements is oral ketones, including a ketone ester (D-beta-hydroxybutyrate and D 1,3-butanediol) sports drink and ketone salts, typically beta-hydroxybutyrate bound to calcium, magnesium, potassium or sodium. A limited body of research indicates that such supplements may improve very long-duration endurance performance, but relatively little is known about their impact on short-duration and high-intensity workouts. Likewise, it is unclear that supplementation with ketones delivers the same benefits as adaptation to a ketogenic diet.

As one can learn from a variety of sources, "ketone bodies are three water-soluble molecules that are produced by the liver from fatty acids during periods of low food intake (fasting), carbohydrate restrictive diets, starvation and prolonged intense exercise… These ketone bodies are readily picked up by the extra-hepatic [outside the liver] tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids."5

In the liver, metabolism of fatty acids for energy, as opposed to ketone bodies, works in conjunction with a normal pattern of activity in the mitochondria, including the citric acid cycle. Ketone bodies are formed when there is not enough glucose from either carbohydrates, including glycogen, or the breakdown of protein to fuel the cycle. Technically, the supply of oxaloacetate is exhausted, at which point the liver produces and exports ketone bodies to tissues that can metabolize ketones fully. In starvation and under very low carbohydrate intake accompanied by restrained protein intake, ketone bodies supply up to 50 percent of the energy requirements for most body tissues and up to 70 percent of the energy required by the brain. The blog mentioned above provides a nice diagram of the cellular steps involved in ketone formation. The author also helpfully points out:

As I have written about eight hundred times in other posts, you do not need to be generating high levels of ketones to be metabolizing fat. The body does not operate in a binary system where the two choices are:

(1) Maintain deep ketosis …or…
(2) Become obese

Just because you're not in ketosis doesn't mean you're somehow not metabolizing fat so that the only other possible destination for it is to be stored.6

Ketone esters and salts can be ingested in an attempt to mimic a ketogenic state and work by elevating blood ketone levels to force the burning fat as fuel while interfering with certain other glycogen-related metabolic pathways. Whether supplements are the equivalent of a ketogenic diet in terms of benefits has been tested in humans only to a limited extent. In animal trials, they are not entirely equivalent and this appears also to be the case in humans. Let's start first with the animal experiments. The positive finding is that a 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague– Dawley rats caused a rapid and sustained elevation of beta-hydroxybutyrate and a reduction of blood glucose.7 No doubt, this represented a shift in the energy source to make use of the ingested ketones.

However, in a comparative trial of a ketogenic diet, ketone supplementation and control diet examining both control and chronic stress conditions, results differed with the intervention. Chronic experiments showed that under control conditions, only the ketogenic diet resulted in pronounced metabolic alterations and improved performance in the novel object recognition test and only the ketogenic diet prevented stress-induced deficits at the end of the trial and improved certain other aspects of performance. The advantage was to the ketogenic diet rather than supplementation in the areas of blood glucose, insulin and overall fat metabolism.8 Ketone supplements in animal models do indeed provide benefits, but not at the level of diet-induced endogenous production.

Thanks to recently published clinical trials, in the area of human athletic performance there now is evidence as to the limitations of ketone supplements. In one study, ten healthy adult males with similar athletic abilities and body mass indices fasted and then consumed either beta-hydroxybutyrate ketone salts or a matched placebo in a randomized order followed by a cycling time trial. Power output on the day participants consumed ketone salts was seven percent lower than on the day they consumed the placebo. As observed by study co-author Jonathan Little, assistant professor in University of British Columbia's (UBC) Okanagan's School of Health and Exercise Sciences, "Elevated blood ketones seem to inhibit the body's use of glycogen, the stored form of glucose, and favours burning fat instead."9,10 A previous study utilizing ketone esters (573 mg/kg athlete body weight) in conjunction with carbohydrate consumption had positive findings of better performance in cycling to exhaustion trials.11

The authors of both studies seem to agree that the ingestion of ketones leads to nutritional ketosis that alters the hierarchy of fuel substrate usage during exercise and it is clear that as the intensity of exercise increases, the demand for carbohydrate as an energy source increases. The ketone salt trial tested shorter and higher intensity training versus the longer period tested in the ketone ester trial, hence these were not entirely apple-to-apple trials. In addition, the ketone ester trial tested roughly 30 grams of ketone ester taken in conjunction with carbohydrate leading to significant benefit versus carbohydrate alone. However, bicycle ergometer time trial performance was only approximately two percent greater using the ketone ester plus carbohydrate versus carbohydrate alone "representing a modest increase in physical capacity in these highly trained athletes, despite significant changes in muscular metabolism." This finding, once again, indicates the difficulty of fully substituting ketones for glycogen-dependent aspects of muscle performance.

The latest studies continue the trend from above. Ingested ketones, for instance, as esters, impaired performance in elite cyclists in ˜31 kilometer laboratory-based time trials on a cycling ergometer programmed to simulate the 2017 World Road Cycling Championships course.12 Achieving overall fat / keto adaptation via dietary means is more successful. Nevertheless, aside from the difficulty in following such diets, keto adaptation to a low carbohydrate, high fat diet requires time. Three weeks clearly is not sufficient even in highly trained athletes such as elite endurance walkers.13 Ten weeks in trained athletes appears to be on the margin, improving feelings of wellbeing, but not performance.14 At least insofar as attested in published trials, a full 12 weeks or more of adaptation is required even in the relatively young (20 subjects, 33 ± 11 years) and vigorous to achieve superior endurance results in comparison to a high carbohydrate diet.15

The above findings lead this author to the observation that although ketone ester-induced ketosis may increase metabolic flexibility during exercise by reducing glycolysis and increasing muscle fat oxidation, the benefits during shorter time periods and/or higher VO2/max demands are either not great or actually negative. Metabolic flexibility in the ester trial, such as it was, required the coingestion of carbohydrate. Without the co-ingestion of carbohydrate, as demonstrated in the other ketone trials (both salt and ester), there was a significant inhibition of the ability to access glycogen stores for energy upon demand.

Metabolic Fitness Supplements

Before looking at individual supplements, it is important

to understand that nutrients that aid metabolic fitness generally fulfill a number of requirements, among them the following:

  • It is helpful to support fat metabolism directly such as through improved transport of fatty acids into the mitochondria for oxidation.
  • Insulin sensitivity must be improved and maintained and insulin levels kept low.
  • The release of fatty acids from fat cells likely is less important than is dis-inhibiting fatty acid metabolism. The first is accomplished with caffeine, yet often with a downside such as increased cortisol levels, hence alternatives to caffeine and other similar stimulants are needed.
  • Inclusion of substances that actively promote fatty acid oxidation is important to help kick-start the body's ability to metabolize fats.
  • Excessive gluconeogenesis by the liver (creation of glucose from glycogen in response to the release of glucagon) should be inhibited to promote fatty acid oxidation as the alternative.
  • With diets that are heavy in alcohol and fat, potential "reverse" effects must be prevented.

The sources of useful supplements are not generic and this should be kept in mind because different production methods lead to different products with different results. The following discussion reviews key nutrients that fulfill one or more of the above requirements.

Potassium-Magnesium Hydroxycitrate
Very few athletes are aware of the benefits of (–)-hydroxycitric acid (HCA) for sports despite some impressive findings in terms of greater endurance and faster recovery plus reduced inflammation. This is because early trials—there were several large ones—failed to produce benefits for reasons that, in retrospect, are obvious. First, calcium HCA and calcium-containing HCA salts exhibit very poor uptake and poor results in comparative trials.16,17,18 To this should be added the "food effect," meaning the finding that consuming food within 30 minutes of ingesting HCA typically reduces uptake by approximately 60 percent. HCA salts under normal delivery never exhibit more than lackluster bioavailability, hence any reduction of that already modest uptake into the system leads to extremely poor results. A third factor is that even seemingly nearly identical HCA salts (as tested by standard high performance liquid chromatography / HPLC) produced by slightly differing production techniques can exhibit up to 10-fold differences in bioavailability.19 Notably lacking in the research literature is any attempt to determine cellular uptake, an issue separate from bioavailability. Published research simply assumes that all uptake issues can be reduced to bioavailability, meaning blood levels, an assumption proven to be invalid with a number of nutritional substances, such as coenzyme Q10.

One way around these uptake problems with HCA is by means of a special liquid delivery. HCA salts normally are not stable in ready-to-drink formats and break apart to yield what is known as a lactone. The HCA lactone leads to good uptake—bioavailability—but little or no benefits because the molecule exhibits the wrong shape.20 A recently issued US patent describes a method that not only stabilizes HCA salts in liquid, but also dramatically improves their bioavailability and physiologic efficacy.21

Properly produced and delivered HCA can lead to striking improvements in early fat utilization for energy, glycogen sparing and increases in endurance. This is in part because HCA helps to control the muscle's selection of fuels, an experimental finding from twenty years ago.22 More recently, using mice as the model, HCA ingestion for 13 days was found to increase fat oxidation and improve endurance exercise time to fatigue by 43 percent compared to a placebo.23 Chronic HCA ingestion alters fuel selection rather than the simple release of fat from stores as is true of lipolysis per se, i.e., the mechanism for HCA is not the same as with caffeine, capsaicin, etc. Second, the combination of HCA plus L-carnitine improves glycogen status in liver and various muscle tissues versus placebo in exercised-trained rodents. Readers will recall that glycogen-related issues bulk large in the performance failings of ketogenic diets and ketone supplements.

What about HCA ingestion in humans? Similar positive endurance results were found by the same laboratory both with untrained men and women and with trained athletes as found in the animal tests. The following trial was conducted in trained athletes leading to significant improvements in endurance:

Subjects [n = 6] were administered … HCA or placebo as a control (CON) for 5 d, after each time performing cycle ergometer exercise at 60% VO2max for 60min followed by 80% VO2max until exhaustion.24

Under the conditions of the trial, time to exhaustion at 80 percent VO2max went from approximately six minutes to approximately 8.5 minutes, which is a remarkable level of improvement. Lactate levels were lower. In evaluating the results, it must be observed that the earlier animal trials indicated that there is a greater shift in metabolism if the ingestion period lasts longer. But note clearly: the HCA salt used in these trials was a pure synthesized trisodium hydroxycitrate, not the usual HCA available as a dietary supplement.25

Another benefit from HCA is as much as a 100 percent improvement in glycogen repletion in muscle after exercise when a post-workout snack is consumed.26

Mango Leaf Extract and Caffeic Acid Enhance HCA's Ability to Improve Fat Metabolism

An issue that almost always is ignored with HCA is that under conditions of accelerated use of fat for energy, such as during fasting or ketogenic diets, there is a cycle that can undermine the compoundfs effects on fat metabolism by activating inside cells the substance acetyl-CoA carboxylase.27 Two compounds that help to prevent this and actually improve fatty acid oxidation are caffeic acid and mangiferin (a constituent of mango leaf).

Caffeic acid is interesting for a number of reasons. For current purposes, it has been shown to improve the ability to metabolize fats for energy and also to promote the ability of glucose to enter cells, i.e., it is insulin sensitizing. In terms of HCA, caffeic acid helps block the actions of acetyl-CoA carboxylase.28 This means that it helps to block the impact of high alcohol intake and high fat intake or fasting on HCA, thus allowing HCA to perform the function of disinhibiting fatty acid metabolism via β-oxidation as mentioned above.

Mangiferin, the primary active component in mango leaf extract, is even more significant than is caffeic acid. With regard to HCA, mangiferin, like caffeic acid, inhibits acetyl- CoA carboxylase. However, matters do not stop there. In various in vitro and animal trials, mangiferin increased fatty acid oxidation. A major finding is that the compound does the same, and safely, in human beings. Overweight patients with hyperlipidemia (serum triglyceride ≥ 1.70 mmol/L, and total cholesterol ≥ 5.2 mmol/L) were included in a double-blind randomized controlled trial. Participants were randomly allocated to groups, either receiving mangiferin (150 mg/day) or an identical placebo for 12 weeks. As reported in the published study,29

A total of 97 participants completed the trial. Compared with the placebo control, mangiferin supplementation significantly decreased the serum levels of triglycerides and FFAs, and insulin resistance index. Mangiferin supplementation also significantly increased the serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine, β-hydroxybutyrate, and acetoacetate, and increased lipoprotein lipase activity.

The increase in β-hydroxybutyrate and acetoacetate as well as lipoprotein lipase activity is a clear indication that mangiferin improves the availability of stored fats and promotes the oxidation of these fats for the production of energy as they became available.

Asparagine, Malate and Aspartates for Energy and Endurance

Some of the best supplements for health and sports have, as it were, slipped under the radar over the years. We tend to be attracted to whatever is "new" to the point of overlooking that these new items often are not actually novel, just older concepts dressed up in new terminology. A good example of this is the great fanfare given to the recent "discoveries" involving nicotinamide riboside. (Caloric Restriction, Fasting and Nicotinamide Riboside TotalHealth Feb 2015)30 Proffered benefits include anti-aging effects, better energy metabolism and endurance.31 Strikingly, both the mechanisms involved and the benefits, upon closer examination, look remarkably similar to the benefits associated with what is known as the malate-aspartate shuttle. The anti-aging benefits, for instance, are similar to those associated with the Chinese herb rock lotus, which activates the enzyme (malate dehydrogenase) linked with this shuttle. (Uncovering the Longevity Secrets of the ROCK LOTUS TotalHealth April 2010)32

For the hard science minded, the malate/aspartate shuttle is a principal mechanism for the movement of reducing equivalents from the cytoplasm to the mitochondria. In other words, this mechanism keeps energy as electrons flowing from the cytoplasm of the cell into the mitochondria and supports the production of adenosine triphosphate (ATP), the basic energy unit of the body. Ketones can play a similar role. As expressed in a recent paper, "cellular energy production depends on the metabolic coenzyme nicotinamide adenine dinucleotide (NAD), a marker for mitochondrial and cellular health. Furthermore, NAD activates downstream signaling pathways (such as the sirtuin enzymes) associated with major benefits such as longevity and reduced inflammation... [a ketogenic diet] will increase the NAD+/NADH ratio."33 (NAD exists in oxidized and reduced forms, NAD+ and NADH.) This process is exactly what the recent discoveries regarding nicotinamide riboside are about. The shuttle also is involved in replenishing oxaloacetate, which was mentioned above with regard to ketogenesis and the Krebs/Citric Acid Cycle. Part of the role of oxaloacetate is shown in the diagram.

Now it just so happens that malic and aspartic acid (the "salts" are termed malate and aspartate) are components of this movement of energy. Malate, aspartate and the compound asparagine are known as oxaloacetate precursors. Many athletes use citrulline malate to help promote performance and reduce fatigue thinking that it is the citrulline that is active although, in fact, it is the malate. For instance, in an animal trial a month of supplementation with L-malate increased swimming time endurance by between 26.1 and 28.5 percent.34 The researchers observed the activities of cytosolic and mitochondrial malate dehydrogenase were significantly elevated in the L-malate-treated group compared with the control group.

As pointed out in the TotalHealth article on the rock lotus, the malate dehydrogenase enzyme takes a period of time to be increased in the cell. A number of acute trials of, for instance, aspartates in athletes, compounds that affect the same shuttle mechanism, failed, but this should have been expected due to basic physiology and one wonders why those researchers even bothered. Under conditions of moderate exertion, supplementation with asparagine and aspartate plus L-carnitine increased time to exhaustion by approximately 40 percent.35 In another animal trial, this time with intense exercise and only the two amino acids, the supplemented group showed higher exercise time, lower blood lactate concentration and a decreased the rate of glycogen degradation compared to control leading to the conclusion that "supplementation may increase the contribution of oxidative metabolism in energy production and delay fatigue during exercise performed above the AT [anaerobic threshold]."36

To be sure, there are skeptics regarding magnesium—potassium aspartates for use as ergogenic aids.37 However, the proposed mechanisms of action until recently have been wrong, the time frame for supplementation (acute rather than chronic), the amounts supplemented, etc., typically have been quite wide of the mark. The key mechanism of action involves the shuttle and oxaloacetate. Interestingly, this mechanism also promotes the proper metabolism of that great enemy of athletes, lactic acid. Lactic acid actually can be converted back into an energy source during exercise. As Ben Greenfield explains things in a wonderful post,38 A significant rate limiting step of converting lactic acid into glucose is the conversion of the molecule Nicotinamide Adenine Dinucleotide (NAD) into Nicotinamide Adenine Dinucleotide Hydrogenase (NADH). So what does this have to do with oxaloacetate? In studies, acute oxaloacetate exposure enhances resistance to fatigue by increasing NAD to NADH conversion and allowing lactic acid to get recycled and converted to glucose at a much higher rate.39

Oxaloacetate is notoriously unstable and difficult to supplement orally. A mixture of its precursors (aspartate salts, asparagine and a malate source) plus an activator of the malate dehydrogenase enzyme (rock lotus) supplemented over a period of time (three to four weeks) is a better way to achieve desired benefits. Finally, another benefit of a mixture of malate and aspartate is that the malate-aspartate shuttle plays a role in the regeneration of L-arginine and the production of nitric oxide.40

Conclusions
Move over, NO (nitric oxide) supplements! Altering muscle fuel selection and increasing the anaerobic threshold are the hallmarks of metabolic flexibility in sports. Greater utilization of stored fatty acids for fuel, reduced lactate accumulation and better recycling, enhanced glycogen stores and an elevation of VO2max before the body's limited stores are called upon without an impairment of carbohydrate utilization is an ideal situation. It is not clear that fulfilling this goal demands artificially elevating blood ketone bodies, either through diet or supplements. Instead, maximizing the efficiency of energy pathways that make use of stored fatty acids and the malate-aspartate shuttle would seem to be not just sufficient, but preferred. Chronic HCA ingestion alters muscle fuel selection and improves glycogen stores, especially in conjunction with L-carnitine. Caffeic acid enhances these actions, as does mangiferin from mango leaf in ways that have been demonstrated in humans to augment the metabolism of both fatty acids and carbohydrates leading to elevated energy production. The malate-aspartate shuttle and the enzyme malate dehydrogenase support oxaloacetate recycling and the efficient operation of the citric acid cycle to sustain fatty acid oxidation and the reconversion of lactic acid to glucose for use as fuel by the muscles. Surely a clincher for this approach is that it promises health and anti-aging benefits, not just improvements in athletic performance.

Endnotes

  1. Supplements Target Ketogenisis and Metabolic Flexibility TotalHealth Magazine
  2. Measuring Ketones
  3. Dehghan M, Mente A, Zhang X, Swaminathan S, Li W, Mohan V, Iqbal R, Kumar R, Wentzel-Viljoen E, Rosengren A, Amma LI, Avezum A, Chifamba J, Diaz R, Khatib R, Lear S, Lopez-Jaramillo P, Liu X, Gupta R, Mohammadifard N, Gao N, Oguz A, Ramli AS, Seron P, Sun Y, Szuba A, Tsolekile L, Wielgosz A, Yusuf R, Hussein Yusufali A, Teo KK, Rangarajan S, Dagenais G, Bangdiwala SI, Islam S, Anand SS, Yusuf S; Prospective Urban Rural Epidemiology (PURE) study investigators. Associations of fats and carbohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet. 2017 Nov 4;390(10107):2050–62.
  4. How To Get Into Ketosis
  5. Ketone_Bodies
  6. Measuring Keytones
  7. Kesl SL, Poff AM, Ward NP, Fiorelli TN, Ari C, Van Putten AJ, Sherwood JW, Arnold P, D'Agostino DP. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond). 2016 Feb 4;13:9.
  8. Brownlow ML, Jung SH, Moore RJ, Bechmann N, Jankord R. Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments. Front Mol Neurosci. 2017 May 15;10:129.
  9. Ketone sports supplements: Good for athletic performance or not?
  10. O'Malley T, Myette-Cote E, Durrer C, Little JP. Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Appl Physiol Nutr Metab. 2017 Oct;42(10):1031–5.
  11. Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256–68.
  12. Leckey JJ, Ross ML, Quod M, Hawley JA, Burke LM. Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Front Physiol. 2017 Oct 23;8:806.
  13. Burke LM, Ross ML, Garvican-Lewis LA, Welvaert M, Heikura IA, Forbes SG, Mirtschin JG, Cato LE, Strobel N, Sharma AP, Hawley JA. Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers. J Physiol. 2017 May 1;595(9):2785–2807.
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  17. Clouatre, D., Talpur, N., Talpur, F., Echard, B., Preuss, H. Comparing metabolic and inflammatory parameters among rats consuming different forms of hydroxycitrate. Journal of the American College of Nutrition 2005;24:429 Abstract.
  18. Clouatre D, Preus HG. Potassium Magnesium Hydroxycitrate at Physiologic Levels Influences Various Metabolic Parameters and Inflammation in Rats. Current Topics in Nutraceutical Research 2008;6(4): 201–10.
  19. Analytical report, Chemical Analysis of HCA in Rabbit Serum Samples, Bálint Analitika, LTD., Budapest, Hungary (2005)
  20. Lowenstein JM, Brunengraber H. Hydroxycitrate. Methods Enzymol. 1981;72:486-97.
  21. United States Patent 9,789,076 Bolus Dose of Hydroxycitric Acid with Glycerol
  22. Saha AK, Vavvas D, Kurowski TG, Apazidis A, Witters LA, Shafrir E, Ruderman NB. Malonyl-CoA regulation in skeletal muscle: its link to cell citrate and the glucose-fatty acid cycle. Am J Physiol. 1997 Apr;272(4 Pt 1):E641-8.
  23. Ishihara K, Oyaizu S, Onuki K, Lim K, Fushiki T. Chronic (-)-hydroxycitrate administration spares carbohydrate utilization and promotes lipid oxidation during exercise in mice. J Nutr. 2000 Dec;130(12):2990–5.
  24. Lim K, Ryu S, Ohishi Y, Watanabe I, Tomi H, Suh H, Lee WK, Kwon T. Short-term (-)-hydroxycitrate ingestion increases fat oxidation during exercise in athletes. J Nutr Sci Vitaminol (Tokyo). 2002 Apr;48(2):128-33.
  25. Lim K, Ryu S, Suh H, Ishihara K, Fushiki T. (-)-Hydroxycitrate ingestion and endurance exercise performance. J Nutr Sci Vitaminol (Tokyo). 2005 Feb;51(1):1-7.
  26. Cheng IS, Huang SW, Lu HC, Wu CL, Chu YC, Lee SD, Huang CY, Kuo CH. Oral hydroxycitrate supplementation enhances glycogen synthesis in exercised human skeletal muscle. Br J Nutr. 2012 Apr;107(7):1048-55.
  27. Triscari J, Sullivan AC. Comparative effects of (--)-hydroxycitrate and (+)-allo-hydroxycitrate on acetyl CoA carboxylase and fatty acid and cholesterol synthesis in vivo. Lipids. 1977 Apr;12(4):357-63.
  28. Tsuda S, Egawa T, Ma X, Oshima R, Kurogi E, Hayashi T. Coffee polyphenol caffeic acid but not chlorogenic acid increases 5'AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle. J Nutr Biochem. 2012 Nov;23(11):1403-9.
  29. Na L, Zhang Q, Jiang S, Du S, Zhang W, Li Y, Sun C, Niu Y. Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial. Sci Rep. 2015 May 19;5:10344.
  30. Caloric Restriction Fasting and Nicotinamide Riboside TotalHealth Magazine
  31. Dellinger RW, Santos SR, Morris M, Evans M, Alminana D, Guarente L, Marcotulli E. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis. 2017 Nov 24;3:17.
  32. Uncovering the Longevity Secrets of the ROCK LOTUS TotalHealth Magazine
  33. Elamin M, Ruskin DN, Masino SA, Sacchetti P. Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism? Front Mol Neurosci. 2017 Nov 14;10:377.
  34. Wu JL, Wu QP, Huang JM, Chen R, Cai M, Tan JB. Effects of L-malate on physical stamina and activities of enzymes related to the malateaspartate shuttle in liver of mice. Physiol Res. 2007;56(2):213–20.
  35. Lancha AH Jr, Recco MB, Abdalla DS, Curi R. Effect of aspartate, asparagine, and carnitine supplementation in the diet on metabolism of skeletal muscle during a moderate exercise. Physiol Behav. 1995 Feb;57(2):367–71.
  36. Marquezi ML, Roschel HA, dos Santa Costa A, Sawada LA, Lancha AH Jr. Affect of aspartate and asparagine supplementation on fatigue determinants in intense exercise. Int J Sport Nutr Exerc Metab. 2003 Mar;13(1):65–75.
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  38. Underground Training Tactics For Enhancing Endurance – Part 2
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Assess your health, your strengths, as well as your problems and bad habits, and look for (ask yourself and take time to listen) the causes or basis of each concern. What are your issues? It’s best to ask for this deeper information and healing in your quiet, meditative place or before sleep to ask your dream imagery to come forth. (Review my Staying Healthy Tips on The Nature of Healing.) This is a time to work on solutions.


Make a list of your goals. What are you willing to work on, work out, and achieve? Do you need to lose weight; have more energy; or find a new doctor/practitioner to help you resolve a problem or illness? Or would a therapist or intuitive be more helpful? For example, you could assess your teeth in January, schedule a Thai massage and an acupuncture or chiropractic session in February, and a five-day health retreat in March. First assess your health budget and see what is covered by insurance if you have it, but also look at what you are willing or able to invest into the health of you and your loved ones.

Review your SNACC habits (sugar, nicotine, alcohol, caffeine, and chemicals). These are common substances that undermine most people’s health, and dealing with them is often the beginning of life improvement. Clearing the daily use (even temporarily) of these habits/abuses/ addictions that takes your vitality is often my first step in the Purification Process (see my book, The New Detox Diet). January is a perfect month to take a vacation from these habits. You may also choose two or three habits to get started. Rather than attempting too much at once, do what you know you can. Step by step still gets you along the health path.

Next, look at your food habits and what you may be overusing that stresses your body and causes reactions. Is it breads and baked goods, refined sugars, or a dependency on drinking cow’s milk or eating cheese? You may not be able to tell this unless you take a break and re-check your response again later. Most of us aren’t fully aware of how specific foods or meals effect us, but we know when we don’t feel fully alive or well, or maybe we want to digest better or reduce some aches and pains or sinus congestion, or just lose a few pounds. Here then, the ideas of The False Fat Diet book can guide you in this important process. A reminder is that this process is more difficult with a stress-filled schedule; thus, you may need to carve out some time both physically and mentally. I like starting my program on a Friday to have the weekend to adjust to the new plan.

Exercise your body, keep it moving! Just because it’s winter, don’t get lazy. Get your activity, but get your rest and sleep as well. Stretch that body and don’t let it get old, get it pumping, and tone those muscles. Cleanse and brush your skin daily as well. Inner clean creates outer sheen. Stay fit and stay healthy.

Do some positive therapies. There are many that can be of help, such as massage and other body therapies; acupuncture, counseling, or a personal reading for guidance. Sometimes merely a walk and talk in the trees with a good friend is all you need to set things right. Try something new or go back to something you liked. New experiences are helpful to growth and healing.

What is your spiritual practice? This may be prayer, religious studies, or meditation. We all come from different backgrounds and beliefs. Our reverence for life, our own and others, is the basic premise for a spiritual life. Treating our body as a temple of Living Spirit provides a motivation to treat ourselves as special and thus feed and care for ourselves in a loving and healthful way. It’s the base and the beginning of a healthy life.

Your career or work is often a core area for your well-being. Are you doing something that is important to you? Do you have a plan for life? Some jobs are what you wish for, others are on the way to somewhere else, and still others are there just to support you and your family. These are all important reasons. If you are not pleased with what you are doing, ask why and what can be done differently. Do you need to review this with a professional counselor? Do you need more education and training? Or will a shift in attitude help you to feel better about your work?

What can you complete this year? What’s been on your mind or sitting around your house? Make a list of a few or more areas that could use some of your valuable energy. (Add these to your list of goals.) This may involve old health habits, a messy room to clean up or rearrange, stuck areas in a relationship, or letting go of old patterns at work. Don’t be afraid to go for it this year.

Make your resolutions and commitments. Begin by looking at the key areas of your life. Health and personal habits, love and relationships, and career or work. And if LOVE moves into all those areas, that’s all the better as you’ll care for yourself and your life, plus your relationships in a positive way. Make more room for love to fill your daily life, and let it be the higher Love. Human love is temporal for many, yet love in the Spirit is everlasting. We are all blessed to share this garden, this Earth, which needs our love and protection. We must take the time to nurture nature, to nourish and flourish.

WRITING ABOUT THE SEASONS AND THEIR AFFECTS ON OUR personal health has been part of my medical message for most all of my 40 years of practice. Connecting to Nature and our own true nature is a key to good health, learning and evolving as we become more self aware and also sensitive to all life on this planet, and our future. Eating from the Earth's bounty with simple foods from our gardens, farms and farmer's markets, and our local stores is principle number one of nutrition. A quote from my book suggests, "Every step away from the garden and orchards is a loss of vitality and nutrition."

I am so happy to see that my first book, Staying Healthy with the Seasons, initially published in 1981, has been influencing the public's health education with this simplest of natural messages. Hippocrates purported to "Pay attention to the seasons of the year and what affects they have on our health." Ideally, we pay attention to the times of seasonal change and look ahead to adapt to this ongoing cycle that has been around since the beginnings of life as we know it.

We have been enjoying the most playful of Seasons this Summer, except for these huge damaging hurricanes and rains in the south. The waters and the fires of this season are clearly out of balance. Is this a unique and isolated problem or one of the many signs of a changing planet in a bit of trouble? Please give it some thought and see if your behaviors can shift to support your best health and then extend that to your family and friends and the entire planet.

My Seasons book and writings involve multiple aspects of our health—as with physical, mental, emotional, and spiritual—along with many disciplines of health, such as Natural and Eastern medicines, foods, herbs, and lifestyle care combined into a Western medicine framework and mindset. I call this NEW Medicine. My 10 tips for Autumn follow and include ideas in many of these areas.

Attuning To Each Part Of The Year And Making appropriate lifestyle changes is key, but the ancient Chinese system also focuses on the time between the seasons—known as the Doyo. This is the period 10 days before and 10 days after each solstice and equinox, when we begin to adapt and make the appropriate changes to step forward into the new season, often with subtle shifts in our diet, exercise program, sleep, and work. Do-Yo literally means "All Have" and these 20-day periods contain a little of each element.

1. As with the gardens, open up to the harvest of your year from the seeds you have planted for your life, and be willing to work hard and discipline yourself as you head into a new season. If you are a student (we are all students of life), get back to your studies. Yes, it is time to shift from the fun and laziness of summer. Nature is so giving, and it helps to be receptive to her and what the Earth has to offer. What do we have to give to life for all the energy, love, and beauty I hope we all receive?

2. Relationships are important to all of us. This is a good time to deepen and clarify our love and family connections. This helps us discover more about our own needs and those close to us, as well as learn to listen to them (both the needs and the people). Also, learn to be alone and listen to your inner guidance and truth. Some folks focus relationships on their computers and TV, car or other electronic devices. Can you still your mind chatter, and let your body breathe deeply to your soul? Give it a try and your spirit will be calmed and can also fly free of the burdens of time.

3. Open to the creative Spirit. We can receive new ideas and actions necessary to fulfill our purpose and move us forward in our life. This can help to improve motivation with new energy and excitement for life. This could be writing about past experiences or our future goals, working on a book or personal story, reading a self-help book and applying it to improve our life, or taking up a new exercise. In other words, start a program now that you can develop and work on into the colder, darker months.

4. The foundation and fortification with our Foods and Diet is an important focus now. Again, this is Harvest time and there are a great many foods—apples and walnuts, sunflower seeds, zucchini and other squash, cabbages, peppers and tomatoes, plus many grains and beans. Learn some new recipes and enjoy good foods. Most of us need more protein and heat generating foods in the colder months, even the energizing spicy peppers such as cayenne and chilies. This will keep our blood and energy moving.

5. Exercise activity is crucial now as in any season. As the weather cools, stretching is even more important, as is having indoor exercises we can do. Yoga and other flexibility-enhancing movements are helpful at keeping us youthful. Remember, we feel as young as our spine is flexible. Our weight work and aerobic activities are vital to staying fit and toned, and strong to support our immune function and circulation. A vital body rarely gets sick.

6. Nutritional supplements are often useful this time of year. Many of my patients add some nutrients that support immune function so as not to pick up whatever is going around. Taking some Echinacea now is helpful as is the Chinese herb, astragalus. Some people prefer the use of mushrooms for immune support, as with maitake and reshitake. Maintaining daily vitamins C and E along with selenium and zinc is also immune protective and helps clear our body of certain toxins. Roots are helpful at tonifying our body at this time. Ginseng is quite good for building strength and endurance. Burdock root is good for the skin and lungs, an area of focus for this season. See the Autumn section of Staying Healthy with the Seasons book for further information.

7. Detoxification is a good idea for early autumn. I am doing a whole month myself and creating a 3-week program in September can provide a great benefit. Can you take a break from some of your routine habits, like caffeine, alcohol, sugar, or cannabis? Doing an effective Detox Diet or avoiding sugar, wheat and dairy for a couple weeks (as I write about in The False Fat Diet book) is often quite revealing and helps us to feel better, lighter and more youthful with greater energy. Since it is getting cooler this season, we will need to exercise and sauna or steam as a means to sweat to clear toxins. Regular sweating is important to health and longevity.

8. Prepare for the cold season. Gather your fuel and food, breathe, and exercise, as you should. In Chinese medicine, the fall season focuses on the lungs and large intestine. Overdoing it can lead to congestion and toxicity, as well as constipation and the clogging of the nose and sinuses. This leads then to upper respiratory infections as the germs grow in the mucus and then inflame the membranes. Staying clean and clear this season along with a healthy immune system will help keep you well. Try a facial steam and breathe in the herbal mist (you can use mints, rosemary, chamomile, lemon verbena, and other herbs) to help clear the sinuses.

9. Should you get any colds or flus, it is best to jump on those immediately. I start with hourly vitamin C of 500–1,000 mg, increased doses of vitamin A (not beta-carotene) 25,000– 30,000 IUs three times daily for just 3–4 days and then lower that dosage to 10–20,000 IUs twice daily for about a week (then take a break since excess vitamin A can be toxic if taken too long). I also use fresh garlic as several cloves at a time dipped in honey and chew them; I may repeat this several times the first day. That is a spicy and aromatic natural antibiotic and immune defender; you can alternately use the odorless garlic caps, several three times daily if you do not want to smell, but they are not quite as effective. You can alternatively press several cloves of garlic into your bowl of soup before you eat, instead of eating the garlic straight. Echinacea and goldenseal alcohol extract can also be used to support immunity and cleanse and disinfect the membranes. Some help may be achieved with olive leaf extract as a mild anti-viral herb. Of course, drink lots of water, herbal teas, and hot soup.

10. Take a rest now because the demanding holiday season is just around the corner. Do not burn your batteries out before November. Kindle your inner flame and firepower, which is protective from the invasion of harsh climates and germs. The winter blues comes partly from a loss of this fire energy. Shifting and balancing with the Seasons is vital to Staying Healthy

Often times after summer, we fall out of the fitness mentality and into the warm comforts of autumnal bliss. Sitting in front of the fire, we forget to move, and the idea of body awareness, movement and breath falls out the window. Instead of playing sports, we begin to watch them.

This fall, what can we do differently? How can we break our habits and increase our mindfulness, and mind-body relationship with itself and our environment?

Below are several ways to keep fitness at the forefront of your mind and body this fall with mindful meditation, exercise for the brain, body and breath.

Each morning, wake up 10 to 15 minutes earlier and spend a little extra time with yourself, focus on your breathing, how the breath enters the body, how it makes you feel as you breathe, and how it exits the body. Pay attention to what happens to the rest of the body as you continue to breathe and continue to do the exercises, playing with the lengths of the inhales and exhales. Make it an enjoyable experience, So that it is an opportunity to learn more about your breath, your body and yourself. There is always an opportunity to expand our mental, physical and emotional selves. And this is one of them.

Meditation is exercise for our brains. The central nervous system, which is run by the brain, controls our body and how it functions, making it a crucial element of our fitness regimes.

Taking care of our brain IS taking care of our body. A study led by Harvard researchers at Massachusetts General Hospital, found that meditating for only eight weeks actually changed the brain’s grey matter. Grey matter is associated with processing information as well as providing nutrients and energy to its neurons. This is why it is said that mediation has shown to improve memory, empathy, sense of self and stress relief.

When school is in session, mental acuteness is just as important for the parent as it is the child. Meditation is proven to sharpen the mind’s focus, lower stress levels and help manage anxiety for the student and teacher, and ultimately the parents. Meditation is key to prepare and react to your children’s energies. When sitting in the car line to pick up the children from school, arrive 20 minutes early to prepare mentally for the sprightly youth to jump into cars with inquisitive and ever-so exuberant minds and bundles of energy bouncing off the walls and in the car seats. Meditation lowers our stress, raises our endorphins and prepares us for anything that will ensue.

For those that require more of a structured schedule to hold us accountable, one can begin a yoga practice. It is a great mental and physical exercise that improves balance. Yoga, meaning union of the breath with the body, brings self-awareness, acceptance and peace with our body-mind relationship, and with our body and mind relationship with it’s surrounding environment. One can begin to practice at home or in a studio with others. The beauty of yoga and life is that the choice is ours. Yoga provides us the freedom to practice it anywhere: outside, inside, by ourselves or with others. And, it all begins with the breath. Yoga begins with the relationship of the breath and body. We clear our minds on the mat and nothing else matters nor does it have to even exist. Only the here and now matter with our body and breath. This form of meditation is a beautiful practice synchronized with movements, certain “asanas” or poses that have specific benefits, depending on what we need during that moment. Yoga is a mental, physical and even for some, spiritual exercise that provides balance for our habitual imbalances, whether that imbalance is in our bodies or minds.

The beauty of yoga is that there are different kinds for different people. The type of yoga that is most fitting at that moment is the type that works for the individual. There is no right or wrong answer. There is what is right now. We are blessed being of this technological age where knowledge is literally overflowing at our fingertips. With the touch of a button, all our questions can be answered. However, with such over saturation and access to knowledge, we can often get overwhelmed and weighted down with all these external stimuli being thrown at us. Which type of yoga is most fitting for us, for me, for you? There is meditative, spiritual, physical, hot, Bikram, Iyengar, Kundalini, power, restorative and many, many more. Thus, we stop searching and go within. We go back to the breath. Let’s keep it simple to keep us moving forward. Keeping it simple is essential moving forward. "One breath at a time" is an inviting and achievable place to start; it is a great motto to adapt so that we can reach our goals and keep moving, keep living and keep breathing. With the breath we remember that, although it appears simple, the benefits greatly outweigh it’s simplicity. Remember that breathing keeps us happy, lowers our stress, focuses our mind, and energizes our body. It is an empowering notion. So much can come from so little.

So this fall, sitting in front of the fire, we can gaze into the golden embers, get lost in their glow and begin to focus solely on our breath and body. As we cherish the relationship with our mind, body and breath, everything else fades away and out of existence. We can ignite life in our bodies, blood cells and brains by a single breath. The only constant in life, that ever present ebb and flow of air, we can begin to improve our relationship with ourselves and those that are around us by beginning a journey of mindful meditation. Exercising our brains and bodies, we fall in love with the mindful meditation, our mind, our bodies and ultimately ourselves. Thus, this fall we begin our fitness journey and the rest of our lives with one breath at a time.

References:

  1. http://www.news-medical.net/health/What-is-Grey-Matter.aspx
  2. http://www.medicaldaily.com/mental-health-benefits-meditation-itll-alter-your-brains-grey-matter-and-improve-319298
  3. http://www.princeton.edu/~achaney/tmve/wiki100k/docs/Grey_matter.html
  4. http://www.webmd.com/mental-health/features/meditationheals-body-and-mind
  5. http://www.yogajournal.com/article/beginners/which-yogais-right-for-you-2/
  6. http://chemistry.about.com/od/chemistryfaqs/f/aircomposition.htm
  7. http://www.teachpe.com/gcse_anatomy/respiratory.php

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