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 compoundfs 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
- Supplements Target Ketogenisis and Metabolic Flexibility TotalHealth Magazine
- Measuring Ketones
- 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.
- How To Get Into Ketosis
- Ketone_Bodies
- Measuring Keytones
- 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.
- 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.
- Ketone sports supplements: Good for athletic performance or not?
- 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.
- 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.
- 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.
- 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.
- Zinn C, Wood M, Williden M, Chatterton S, Maunder E. Ketogenic diet benefits body composition and well-being but not performance in a pilot case study of New Zealand endurance athletes. J Int Soc Sports Nutr. 2017 Jul 12;14:22.
- McSwiney FT, Wardrop B, Hyde PN, Lafountain RA, Volek JS, Doyle L. Keto-adaptation enhances exercise performance and body composition responses to training in endurance athletes. Metabolism. 2017 Dec 2. pii: S0026-0495(17)30328-1.
- Louter-van de Haar J, Wielinga PY, Scheurink AJ, Nieuwenhuizen AG. Comparison of the effects of three different (–)-hydroxycitric acid preparations on food intake in rats. Nutr Metab (Lond). 2005 Sep 13;2(1):23.
- 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.
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