For Sports and Health
Most readers who have heard of ketosis and ketogenesis
likely associate the concepts with dieting and the works of Dr.
Robert C. Atkins (Dr. Atkins’ Health Revolution, 1989; Dr. Atkins’
New Diet Revolution, 1992) that launched a bit of a movement
in the 1990s. Much less well known is the role of ketosis in
sports and the importance of being able to enter ketosis as an
aspect of metabolic flexibility, meaning the ability to rapidly and
easily shift between carbohydrates and fats as fuel substrates
to match, on the one hand, dietary sources of calories and, on
the other hand, particular physical demands for energy. In fact,
the health implications of metabolic flexibility are significant
and are related to the body’s degree of insulin sensitivity and
thereby to the components of the metabolic syndrome. The
latter condition often is defined as being based on insulin
resistance and associated with abdominal (central) obesity,
elevated blood pressure, elevated fasting plasma glucose, high
serum triglycerides and low high-density lipoprotein (HDL)
levels. This way of looking at matters makes ketogenesis and
metabolic flexibility major determinants of health. One does
not need to be diabetic or even pre-diabetic for these issues to
be important, a point that Harry Preuss, MD and various coauthors,
including myself, make in a recent article intended for
practicing physicians, “Importance of Fasting Blood Glucose in
Screening/Tracking Overall Health.”1,2
Not only athletes for reasons having to do with competition,
but also non-athletes for reasons of health likely would benefit
from some form of supplement protocol or other approach
that can achieve ketogenesis and maintain metabolic flexibility
without depending entirely on the diet. Indeed, achieving
ketosis via diet alone is hard to maintain over the long haul for
a variety of reasons. Eating mostly protein and fat may sound
like a treat at the beginning, but highly restricting all sources of
carbohydrates quickly leads to a boring diet and even limited
social interaction because few social events are built around
ketogenic snacks! It also means avoiding many or most sources
of phytonutrients, not eating adequate fiber for gut health and
bowel regularity, probably inadequately eliminating toxins via
the bile route in the stool, and even ramping up production
of the hormone cortisol.3 Extreme ketosis leads to unpleasant
breath (acetone breath) although this is not an issue with
moderate and healthy ketogenesis.
Background on Ketosis and Ketogenic Diets
There are only two primary sources of energy, carbohydrates
and fats. If needed for energy, protein can be broken down to
yield a carbohydrate component, not a fatty acid component.
Ketosis refers to the state in which the body meets its energy
requirements largely through the oxidation of ketone bodies.
These build up in the blood when glucose is not being used for
energy and even the brain can run on ketone bodies. Glycolysis
is the opposite number to ketosis in that it refers to the oxidation
of glucose, for which all carbohydrates ultimately are a source,
for energy. People sometimes associate ketosis with diabetes,
but ketosis is a nutritional process whereas in diabetes the body
either lacks sufficient insulin or cannot respond properly to
insulin and therefore builds up ketone bodies due to a failure of
metabolism while at the same time not properly harnessing fats
for fuel. There is plenty of evidence to the effect that ketogenic
diets can be healthful. Traditional Eskimo diets consisted almost
entirely of raw meat and blubber (fat) and yet the Eskimos did
not exhibit diabetes. Similarly, for certain neurologic conditions
children are raised from early life into their thirties or later
with completely normal physiologic and mental development
without eating any carbohydrates at all.
Athletes and some "paleodieters" speak of keto-adaptation,
which means simply moving the metabolism to preferentially
accessing stored fats as fuel sources rather than depending on
glucose. The body has quite limited stores of glycogen or "animal
starch" stored primarily in the liver in contrast to virtually
unlimited calories stored as fats. A quite standard assessment
is that there may be 400 grams of glycogen in the liver and
another 100 grams in the muscles. Glycogen is associated with
water on a 1:3 to 1:4 ratio. 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.
High fat diets were employed at the turn of the century to
treat Type I diabetes, the form that begins in childhood with
the destruction of the insulin-producing cells of the pancreas.
Since the body can and will produce its own blood sugar from
protein in order to feed the brain, there is always some role for
insulin in the body regardless of the diet followed. Needless to
say, those with juvenile diabetes almost invariably died young
until the discovery of insulin.
In adult-onset or Type II diabetes, which typically begins
fairly late in life and with those already overweight, diet and
exercise often can completely control the problem. This and
other clues have led a number of researchers to suspect that
excess weight gain is related to insulin production either directly
or indirectly, as discussed briefly above. Dr. Robert C. Atkins was
one of the first to popularize the notion of dieting by bypassing
the insulin mechanism through eliminating most carbohydrates
from the diet while continuing to consume both proteins and
fats. Atkins' Diet is both high in protein and high in fat.
High protein, low fat/very low carbohydrate diets have
been common for some time, but not with the particular
justification that they bypass the insulin mechanism. Generally
the justifications have had to do with energy production, or
rather the lack of it on these diets. In the Stillman Diet, for
instance, it was argued that protein molecules are so large that
they use up extra energy as a food for the body. This diet calls for
the drinking of at least eight glasses of water a day, which truly
is necessary to remove the waste products of excess protein
consumption and from the oxidation of the body's own fats.
Very similar is the famous Scarsdale Diet, designed for use for
only two weeks at a time. Both strictly limit carbohydrates and,
somewhat less strictly, fats. Both do reduce weight in the short
term, but such large amounts of protein are hard on the body.
In contrast to these, the Dr. Atkins' Diet allows for unlimited
amounts of both proteins and fats, but for restricted amounts
of carbohydrates according to the theory that a faulty insulin
mechanism is the cause of excess weight. A more limited form
of this ketone-based diet popularized at about the same time as
the Atkins Diet is presented by Dr. Calvin Ezrin in The Endocrine
Control Diet (1990).
Athletes long have experimented with ketogenic diets. For
instance, during the 1990s a number of top bodybuilders in the
World Bodybuilding Federation adopted a diet similar to the one
Atkins uses (roughly 40 percent of calories from protein and
60 percent from fat) in order to cut body fat and build muscle.
These individuals were all undertaking extremely hard physical
labor, so the diet itself cannot be a source of fatigue, but must
in fact supply considerable energy.4 Nevertheless, even major
competition class athletes ultimately generally give up on
strict ketogenic diets. 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."5
Ketogenesis with Supplements
Can ketogenesis be achieved using a more normal diet with
the help of supplements? The answer appears to be "yes."
Nevertheless, there are important considerations, among which
are the following:
- 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¨C 30 percent protein, 30¨C40 percent carbohydrate and 30¨C40 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."
- 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 disinhibiting 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.
A small number of supplements, especially if taken together,
may fulfill the above requirements and actually have been tested
successfully in a pilot case. The subject in question was able to
consume a normal diet, indeed one that included quite a bit
of alcohol, by relying on only four supplements to remain in
moderate ketosis during much of the day: hydroxycitric acid,
wild bitter melon extract, sesame lignan extract and green
coffee bean extract. The sources of these supplements were
not generic and this should be kept in mind because different
production methods lead to different products with different
results. Published comparative trials, for example, with
hydroxycitric acid have shown this definitively.
The key component in supplement-support ketogenesis is
(-)¨Chydroxycitric acid (HCA). That some forms of properly
manufactured HCA can be used to encourage ketogenesis has
been known at least since 2000. In that year, Ishihara published
that HCA ingestion for 13 days increased fat oxidation and
improved endurance exercise time to fatigue by 43 percent
compared to a placebo in mice.6 Over the following few years,
three studies by Lim and others in trained athletes demonstrated
that ingestion of HCA enhances endurance performance via
increasing fat oxidation and sparing glycogen utilization during
moderate intensity exercise. In fact, in trained athletes HCA
ingestion for five days shifted fuel selection to fat oxidation
at both 60 percent and 80 percent VO2max during exercise.7
Lim further demonstrated a number of significant findings.
First, using mice as his model, he showed that chronic HCA
ingestion alters fuel selection rather than the simple release of
fat from stores as is true of lipolysis, i.e., mechanism for HCA
is not the same as with caffeine, capsaicin, etc. Second, Lim's
review data that showed that the combination of HCA plus
L-carnitine improves glycogen status in liver and various muscle
tissues versus placebo in exercised-trained rodents. Since the
publication of Lim's papers, this finding has been repeated
more than once with human athletes. Although L-carnitine
improves the effect, it is not necessary.8 Third, Lim in his
studies employed a pure synthesized trisodium hydroxycitrate
salt rather than commercial calcium or calcium-potassium
HCA salts, which did not yield his results. As is true of many
herbal products, the benefits of HCA are highly dependent
upon how the item is prepared. The acid must be stabilized by
the addition of high pH ions (basic or alkali), such as those of
potassium, magnesium or calcium. Using the wrong stabilizing
counter-ions results in little or no activity. In the case of the acid
derived from Garcinia cambogia and related sources, adding any
calcium at all reduces some desired benefits and blocks other
benefits entirely.9 This fact has been verified by more than one
Another benefit of HCA that supports ketogenesis is its
impact on insulin sensitivity. At the 2005 Annual Meeting of the
American College of Nutrition for the first time it was reported
that the potassium-magnesium HCA salt in an animal model
gave the same blood glucose regulation as found in the control
arm of the test while almost literally cutting insulin levels in
half.10 The same study demonstrated that this salt dramatically
improved glucose clearance from the blood, lowered systolic
blood pressure and also lowered several key indicators of
inflammation, including C-reactive protein and tumor necrosis
factor-alpha (TNF-alpha). In contrast, the potassium-calcium
salt exerted no effect upon insulin and blood sugar regulation
and only very poorly influenced blood pressure.11 In the areas of
insulin metabolism, glucose regulation and blood pressure, the
proprietary potassium-magnesium salt was between five and
seven times as active as the potassium-calcium salt of the fruit
acid. A paper just published this year also indicates that HCA
may help to regulate thyroid hormones and promote muscle
Wild Bitter Melon Extract and Sesame Lignan Extract
As indicated above, HCA appears to be extremely useful in
freeing the body's metabolism regulators to allow a shift
towards preferentially oxidizing fatty acids for energy. Increasing
insulin sensitivity and reducing insulin levels removes one of
the primary brakes on fatty acid metabolism. A complement to
these actions is direct activation of fatty acid oxidation. Both
wild bitter melon and sesame seed lignans help to do just this.
Bitter melon previously has been discussed in these pages
under the title, "Going WILD with Bitter Melon for Blood Sugar
Support."13 As noted in that article, it has been found that
extracts of bitter gourd activate cellular machinery to regulate
energy production (technically, AMP-activated protein kinase or
AMPK) and the way that fats are handled by the liver. These
components can account for as much as 7.1 g/ kg of the dried
The sesamolin lignan found in sesame seeds (but not in
most extracts) likewise increases fat metabolism. As pointed
out in an important study, the "[e]ffects of sesamin and
sesamolin (sesame lignans) on hepatic fatty acid metabolism
were compared in rats. Sesamolin rather than sesamin can
account for the potent physiological effect of sesame seeds
in increasing hepatic fatty acid oxidation observed previously.
Differences in bioavailability may contribute to the divergent
effects of sesamin and sesamolin on hepatic fatty acid
oxidation. Sesamin compared to sesamolin was more effective
in reducing serum and liver lipid levels [with]sesamolin more
strongly increasing hepatic fatty acid oxidation." "Sesamolin
rather than sesamin can account for the potent physiological
effect of sesame seeds in increasing hepatic fatty acid oxidation
observed previously."14 "...gene expression of hepatic enzymes
involved in fatty acid oxidation [was] much stronger with
episesamin and sesamolin than with sesamin¡[serum] half
lives of 4.7±0.2, 6.1±0.3 and 7.1±0.4 h for sesamin, espisesamin
and sesamolin, respectively...15
Green Coffee Bean Extract
After meals, up to 70 percent of the glucose from food is
stored in muscle and other lean tissues. However, moment-to-moment
regulation of blood glucose typically is handled by the
liver. It does this via two processes, both of which are highly
regulated. Gluconeogenesis generates glucose from certain noncarbohydrate
carbon substrates, including certain amino acids
and lipid components, such as triglycerides. Glycogenolysis is
the freeing of glucose from glycogen stores. In the liver, but
not the muscles, the hormone glucagon is involved. The liver
also uses the enzyme glucose-6-phosphatase. With aging and
as the metabolic syndrome develops, regulation of these two
processes becomes impaired. Dysregulation is a particularly
significant issue in diabetes.
Coffee, especially green coffee extracts, supply chlorogenic
acid, which inhibits the glucose-6-phosphatase enzyme.16,17
Chlorogenic acid also inhibits glucose absorption from the
intestinal tract and thus reduces after meal blood glucose
Ketogenesis requires that the body preferentially use fatty
acids for fuel. This cannot happen if either gluconeogenesis or
glycogenolysis is not under proper control.
L-Carnitine and Astaxanthin
L-carnitine is a nutrient that, among other things, helps to
shuttle fatty acids into the mitochondria for oxidation. In the
discussion of HCA above it was noted that the combination
of HCA and L-carnitine greatly improves the replenishment
of glycogen stores after exercise. Unfortunately, tissue levels
of L-carnitine are highly regulated and difficult to elevate to
the extent necessary for ergogenic benefits in athletes. HCA
improves L-carnitine metabolism by increasing uptake.HCA is an
insulin memetic as well as an insulin sensitizer. HCA also shifts
the body towards metabolizing fats, which makes L-carnitine's
job easier. Another approach is to supplement with astaxanthin.
Astaxanthin (≥4 mg/d) has been shown to reduce lactic acid
accumulation during exercise, improve fatty acid oxidation and
maintain better blood glucose levels while improving endurance.
The mechanism may involve carnitine palmitoyltransferase I.18,19
Studies have demonstrated the importance of metabolic
flexibility for maintaining cardiovascular health and reducing the
risk of developing metabolic syndrome components. Likewise,
studies have shown that the related ability to enter ketosis as
needed for athletic purposes can render rich ergogenic rewards.
Nevertheless, enabling ketogenesis or keto-adaptation, however
desirable this might be, through dietary measures alone
under modern circumstances in Western countries is not only
inconvenient, but downright difficult. Fortunately, it is possible
to enable keto-adaptation through the use of appropriate
supplements. These include properly manufacture HCA salts,
wild bitter melon extract, sesame lignans and green coffee bean
extracts. L-carnitine and astaxanthin are two more supplements
that fit into this schema.
- Preuss HG, Mrvichin N, Clouatre D, et al. Importance of Fasting Blood Glucose in Screening/Tracking Overall Health. The Original Internist. 2016, March:13-15,17.18.
- Bjornholt JV, Erikssen G, Aaser E, et al. Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men. Diabetes Care. 1999 Jan;22(1):45.9.
- Sears B. Anti-inflammatory Diets. J Am Coll Nutr. 2015;34 Suppl 1:14.21.
- Mauro DiPasquale, M.D., "Let the Fat be with You: The Ultimate High-Fat Diet," Muscle Magazine International (July and September 1992); "High Fat, High Protein, Low Carbohydrate Diet: Part I," Drugs in Sports 1, 4 (December 1992) 8.9.
- 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.
- 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.
- 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.
- 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. See also notes 18 and 19.
- 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.
- Clouatre D, Preuss 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.
- Han N, Li L, Peng M, Ma H. (-)-Hydroxycitric Acid Nourishes Protein Synthesis via Altering Metabolic Directions of Amino Acids in Male Rats. Phytother Res.2016 May 4. doi: 10.1002/ptr.5630.
- Lim JS, Adachi Y, Takahashi Y, Ide T. Comparative analysis of sesame lignans (sesamin and sesamolin) in affecting hepatic fatty acid metabolism in rats. Br J Nutr. 2007 Jan;97(1):85.95.
- Ide T, Lim JS, Odbayar TO, Nakashima Y. Comparative study of sesame lignans (sesamin, episesamin and sesamolin) affecting gene expression profile and fatty acid oxidation in rat liver. J Nutr Sci Vitaminol (Tokyo). 2009 Feb;55(1):31.43.
- Henry-Vitrac C, Ibarra A, Roller M, Merillon JM, Vitrac X. Contribution of chlorogenic acids to the inhibition of human hepatic glucose-6-phosphatase activity in vitro by Svetol, a standardized decaffeinated green coffee extract. J Agric Food Chem. 2010 Apr 14;58(7):4141.4.
- Bassoli BK, Cassolla P, Borba-Murad GR, et al. Chlorogenic acid reduces the plasma glucose peak in the oral glucose tolerance test: effects on hepatic glucose release and glycaemia. Cell Biochem Funct. 2008 Apr;26(3):320.8.
- Malmsten C, Lignell A. Dietary Supplementation with Astaxanthin-Rich Algal Meal Improves Strength Endurance; A Double Blind Placebo Controlled Study on Male Students. Carotenoid Science. 2008;13:20.22.
- Aoi W, Naito Y, Takanami Y, Ishii T, Kawai Y, Akagiri S, Kato Y, Osawa T, Yoshikawa T. Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification. Biochem Biophys Res Commun. 2008 Feb 22;366(4):892.7.