Pyruvate: A Comprehensive Review ©1997-2009

By William R. Sukala, MSc. Clinical Exercise Physiologist
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INTRODUCTION

Pyruvate is a dietary supplement targeting both sedentary and active individuals. The most
popular claims for pyruvate center about its purported ability to: 1) "significantly" increase fat and
weight loss; 2) improve exercise endurance capacity; 3) effectively reduce cholesterol, and; 4)
serve as a potent antioxidant. However, these contentions are based mainly on faulty
extrapolations of preliminary or inconclusive evidence.

Multi-level marketing supplement distributors and internet entrepreneurs, most without any
formal training in nutrition, are leading the campaign with reckless abandon and little regard for
the accuracy of their claims. Anecdotal testimonials from "satisfied" users permeate everything
from internet websites to fitness magazines to television infomercials. While the mere mention of
"scientific studies" is enough to impress the lay consumer, a critical review of the original
research reveals a very different picture.

WHAT IS PYRUVATE?
Pyruvate is a three-carbon (triose) ketoacid produced in the end stages of glycolysis. It can be
reduced to lactate in the cytoplasm or oxidatively decarboxylated to acetyl CoA in the
mitochondrion (13). Simply, it is a product of sugar metabolism.

COMPARISON OF POPULAR CLAIMS TO ACTUAL RESEARCH
Claim: "Significantly increase fat loss by 48% and weight loss by 37%!"
Two human studies evaluated pyruvate's role as a fat and weight reductant (11, 12). In both
investigations, treatment subjects lost more fat and weight than the control group, but only one
found these percentages (11). Considerably smaller changes (23% greater fat loss and 16%
greater weight loss) were noted in the other study (12). This claim is particularly misleading to
consumers since these "significant" percentages actually amount to only a few pounds. The
widely popular 48% translates to a mere 1.3 kg or 2.86 lbs and 37% is really 1.6 kg or 3.52 lbs--
hardly the significant losses dieters have come to expect. Furthermore, these percentages have
no practical relevance outside the context of a research article (How does a consumer quantify
48 and 37%?). A formal research environment differs from the real world in that the latter
presents many confounding variables, so results (or lack thereof) may be attributable to factors
unrelated to pyruvate supplementation.

The experimental protocol was extremely exclusive. All subjects were: 1) morbidly obese
women; 2) housed in a metabolic ward for 21 days; 3) confined to bed except for walking to the
restroom and kitchen; and 4) restricted to a 500 to 1,000 kcal liquid diet. As such, the results of
these studies are specific to these criteria and cannot be reliably generalized to the population at
large.

The relatively small differences observed in treatment subjects were induced by dosages
considerably larger (22 to 28 grams of triose) than those available to consumers. Commercially
available preparations provide about 500 mg to 1 gram of pyruvate, usually taken a few times a
day for a daily intake of 3 to 5 grams. To date, no studies have been performed with such benign
dosages.

Claim: "Prevents fat regain and eliminates "yo-yo" effect"
This claim is based on a single study (5). Initial weight loss was induced by a 310 kcal diet
followed by subsequent hypercaloric refeeding supplemented with large amounts of triose (15
grams of pyruvate and 75 grams of dihydroxyacetone). The treatment group gained 1.8 kg or
3.96 lbs (36%) less weight and 0.8 kg or 1.76 lbs (55%) less fat than the placebo group.
However, for a number of reasons, these results cannot be accurately ascribed to the general
public.

This study also employed morbidly obese women housed in a metabolic ward for 21 days while
refraining from all physical activity. While results were statistically significant, they were
physiologically negligible; that is, from an absolute standpoint the changes were relatively
inconsequential.

Claim: "Significantly improve exercise endurance by 20%."
Stanko and colleagues found triose-supplemented (75 grams dihydroxyacetone and 25 grams
pyruvate) subjects increased time to exhaustion by 20% during arm and leg ergometry protocols
(9, 10). Unfortunately, these results are far from conclusive and should be considered, at best,
preliminary.

First, both studies employed small numbers of untrained males; no large-scale investigations
using trained subjects have been performed. Well-trained athletes present less intra- and intersubject
variability in performance which can increase the statistical power of the trial (2).
Second, the large amounts of pyruvate needed to elicit improvements ranged from 20 to 100
times the amounts found in supplements. Unfortunately, there is no evidence that the minuscule
doses available to consumers exert any physiological effect.

Some marketers have generalized that pyruvate supplementation can improve performance
across a broad spectrum of activities. However, such quantum leaps are inappropriate since
these results are specific to arm and leg ergometry protocols. Different activities impose specific
physiological and biochemical demands, and can vary in their motor unit recruitment patterns.
The point is that no one knows what effect it has, if any, on other sports; claims to the contrary
are based solely on speculation.

Claim: "Shown to lower cholesterol."
Two studies (7, 8) investigated pyruvate's role as a cholesterol reductant; however, only one
showed any change (8). Treatment subjects took (large doses) 36 to 53 grams of pyruvate over
the course of six weeks while consuming a high fat (45 to 47%), high cholesterol (560-620 mg)
diet. While the results in this study (8) showed small changes in total cholesterol (4%) and LDL
cholesterol (5.4%), these effects were negated when subjects consumed a low-fat, low
cholesterol diet (7).

It is not valid to state that pyruvate has been conclusively proven to reduce plasma lipids. While
popular marketing literature leads consumers to believe that this is an effective treatment for
hyperlipidemia, one study does not constitute a substantial body of evidence. No legitimate
public health agency would ever make broad recommendations based on such scant evidence.

Claim: "Improves cardiac function and lowers blood pressure."
In one of the cholesterol studies (8), heart rate and diastolic blood pressure decreased by 9 and
6%, respectively; however, these changes were incidental to the research objectives and were
not the main focus of the study. These preliminary findings should not be considered conclusive.
Rather, they can serve as the impetus for future studies in this capacity. Unfortunately,
marketers do not address this in their promotional literature.

Claim: "Pyruvate is a powerful antioxidant!"
The effect of pyruvate as an oral antioxidant has never been investigated. Two studies (1, 3)
have shown its potential as an in-vitro antioxidant under tightly controlled experimental
conditions; but extrapolating these results to humans is particularly misleading since isolated
tissue culture (1) and post-ischemic heart models (3) are not the same as human trials. This is
not to discount the relevance of these clinical findings; rather, the practical application of
pyruvate as an oral antioxidant remains to be established.

Claim: Pyruvate is a "natural alternative" to Phen/Fen
This claim capitalizes on the American public's fear and distrust of the pharmaceutical industry.
To understand why this comparison is invalid, it is necessary to look at how drugs and
supplements are evaluated. A regulated drug must undergo extensive testing to evaluate it's
safety, toxicity, side effects. With the passage of the Dietary Supplement and Health Education
Act of 1994, nutrition supplements can be sold to consumers without being tested for safety,
efficacy, purity, or potency--although many consumers mistakenly believe that simply because
it's available it must be safe and effective.

Even if they were on par with each other, pyruvate has never been clinically tested or proven to
be more effective than Phen/Fen (or any other prescription weight loss medication). In light of
Phen/Fen's 1997, removal from the market, many marketers are quick to trumpet its
“effectiveness” over regulated pharmaceuticals. Clearly, a reliable comparison cannot be made.

FALSE AND MISLEADING CLAIMS
While the most popular claims are supported by limited evidence, there are many more with no
basis in fact whatsoever. Some are downright false and others are deceptive half-truths.
Claim: "Shown to be a more potent fat burner than hydroxycitric acid (HCA) and chromium
picolinate combined."

This claim is blatantly false since no studies have ever compared pyruvate to HCA and
chromium picolinate--chromium and HCA have not been conclusively proven to enhance fat
oxidation. There is absolutely no merit for this claim, yet it can be found on promotional literature
as "clinically proven."

Claim: "Pyruvate is found naturally in the body and in a variety of foods."
Pyruvate is a normal constituent of human and plant metabolism; however, the term "natural" is
ambiguous and therefore confers a deceptive stamp of approval to the unsuspecting consumer.
This tactic is grounded in the "if-it's-natural-it-must-be-safe-and-effective" myth. Unfortunately,
natural does not mean safe or effective—E. coli and rattlesnake venom are both “natural” but
that doesn’t mean they promote health and vigor.

Claim: "Pyruvate has been clinically proven safe with no side effects."
In all human trials (5, 7-12), some subjects receiving large doses of pyruvate experienced
gastrointestinal distress in the form of diarrhea, borborygmus, and flatulence. It is likely that
consumers do not experience these symptoms due to the benign amounts of pyruvate found in
supplements rather than manufacturers' formulations.

Claim: "patented 4 times over."
A patent on a product does not mean it works; anyone can patent anything. Wise consumers
should dismiss patents as "proof" of efficacy. The only true guarantees are big profits for the
companies selling the product.

TESTIMONIALS
Emotional testimonials are often employed by supplement promoters, usually as a way of
downplaying one's natural skepticism--the "be like Mike" syndrome. Unfortunately, testimonials
have no scientific merit since they do not separate cause and effect from coincidence. Let there
be no doubt about it; testimonials are very convincing. One should be skeptical when a product
distributor says, "it worked for me, it can work for you." Yes, maybe the promoter experienced
some type of change, but there is no way to verify if it was a result of the product. For example, if
one takes the pyruvate while reducing calories and engaging in physical activity, there is no way
to differentiate whether the weight loss was caused by the diet and exercise or the supplement.
Again, there is no separation of cause and effect from coincidence.

There is no way to verify the validity of testimonials. A consumer would not be able to confirm if
the people are, in fact, real, or they've been paid for their endorsement. In the case of pyruvate,
conflicts of interest abound. A pro-pyruvate article appeared in Muscle and Fitness Magazine (4)
and quickly became a highly prized marketing tool for promoters. However, the numerous
testimonials listed in the article are questionable.

According to the article:
”Terry Newsome, a 38-year old executive from Westlake California, has battled obesity for two
decades, touts the effects of pyruvate. I've lost 39 pounds in less than 40 days. Other than the 5
grams of pyruvate, my eating and exercise habits have remained the same and I feel better than
I ever dreamed possible.....”

Ironically, Terry Newsome, at the time the article appeared on news stands, was president of
Med-Pro industries, the company that holds four patents on pyruvate. Since he has direct
involvement in the company, this testimonial cannot be considered objective. Even if he did lose
39 pounds in less than 40 days, there is no way to be certain the entire composition was fat.
The First Law of Thermodynamics (Conservation of Energy) holds that energy cannot be created
or destroyed, only transformed from one form to another. So it is unrealistic to believe he could
have expended an additional 3,500 kcal (1 lb of fat = 3500 kcal) above and beyond his daily
caloric requirements, especially since he did not change his eating and exercise habits. And 5
gram doses of pyruvate have never been used in any published clinical research.

Famous athletes double as popular marketing tools for ergogenic aids, the obvious implication
being that average consumers will perform at elite levels. The article states: “Of note, Olympic
gold-medal gymnast Shannon Miller and her coach, Steve Nunno, are expected to endorse
pyruvate because of the increased energy Miller experienced with the product. Though not part
of a scientific study, Miller says that pyruvate helped energize her just days before the 1996
Olympics.” This passage is misleading to consumers for a number of reasons.

First, the terms "increased energy" and "energize" are ambiguous and can be subjectively
defined many different ways (for some, "energy" is just getting out of bed; for others it might be
running 15 miles).

Second, elite athletes operate at such high physiological levels of performance that there is very
little room for improvement. Untrained individuals, on the other hand, have sufficient room for
improvement, with or without supplements. Third, the women gymnasts earned their gold medals
as a team. Clearly Ms. Miller contributed her part, but there is no way to know if pyruvate had
any effect on the final results.

Lastly, gymnastics differs markedly from steady-state endurance exercise--the motor unit
recruitment patterns and metabolic demands of gymnastics are not the same as arm and leg
ergometry protocols (9, 10). So there is no way to tell how much pyruvate contributed to each
activity, if at all.

COMMON MARKETING PLOYS
Pyruvate promoters have accessed every available media outlet. By far, the internet is the
preferred marketing method, allowing pyruvate to be marketed quickly and inexpensively. People
are inculcated by internet message boards, news groups, list-serves, and chat rooms, most of
which lead to unsolicited junk e-mail. Unfortunately, consumers have absolutely no way of
verifying what's legitimate since anyone can exploit the internet.

Print advertisements line the pages of magazines, newsletters, daily and weekly newspapers,
and many supplement industry catalogs. Eye-catching, glossy ads featuring slender, tan bodies
are often paired with the usual grandiose claims.

Infomercials trumpet pyruvate’s benefits via the late night airwaves. As with any paid
endorsement, their content should be viewed with skepticism. Promotional audio tapes are also
making the rounds. Essentially, they mirror print advertisements, but are a convenient way to
target the non-reader.

COST
Pyruvate does not come cheap. Firms sell pyruvate supplements for anywhere from $50 to $65
per bottle of 120 capsules. Usually for a nominal fee, anyone can become a multi-level
marketing distributor which would further lower the price even more. No matter how you look at
it, this is an expensive price to pay for a product that hasn't been conclusively proven to do
anything.

THE BOTTOM LINE
A number of irrefutable certainties exist: 1) The minuscule doses available in commercial
supplements have not been proven effective in any available research. No dose-response
relationship has been established so there is no way of knowing the minimum effective dose; 2)
Existing research does not conclusively support marketers' claims, many of which are based on
faulty extrapolations from inconclusive, preliminary findings; and 3) Most studies were conducted
by Ronald Stanko and have not been replicated by other researchers in other laboratories under
various conditions in various sample populations. But don't expect marketers to readily embrace
these facts. Whether pyruvate works or not seems to be unimportant to marketers. Customers
will continue to be exploited for profit as long as the existing volume of misinformation
surrounding pyruvate persists.

Perhaps all the attention stirred by promoters will spark the interest of other researchers and
may eventually answer some of the questions presented in this article. Existing research is
valuable in that it can serve as a preliminary foundation to guide future investigations.
Nevertheless, at this point in time, pyruvate should be dismissed as nothing more than a toogood-
to-be-true supplement.

REFERENCES
1. Borle, A., and R.T. Stanko. Pyruvate reduces anoxic injury and free radical formation in
perfused rat hepatocytes. J. Appl. Physiol. 270: G535-G540, 1996.
2. Burke, L., and P. Heely. Dietary supplements and nutritional ergogenic aids in sport. In
Clinical Sports Nutrition, L. Burke, and V. Deakin (Ed.). Sydney, AUS: McGraw-Hill, 1994, pp.
227-284.
3. DeBoer, L.W.V., P.A. Bekx, L. Han, and L. Steinke. Pyruvate enhances recovery of rat hearts
after ischemia and reperfusion by preventing free radical generation. J. Appl. Physiol. 265:
H1571- H1576, 1993.
4. Roufs, J.B. Pyruvate: Does it amp endurance and burn more fat? Muscle and Fitness. 57: 87-
88, 195- 197, December 1996.
5. Stanko, R.T., and J.E. Arch. Inhibition of regain in body weight and fat with addition of 3-
carbon compounds to the diet with hyperenergetic refeeding after weight reduction. Int. J. Obes.
20: 925-930, 1996.
6. Stanko, R.T., H. Mendelow, H. Shinozuka, S.A. Adibi. Prevention of alcohol-induced fatty liver
by natural metabolites and riboflavin. J. Lab. Clin. Med. 91: 228-235, 1978.
7. Stanko, R.T., H.R. Reynolds, R. Hoyson, J.E. Janosky, and R. Wolf. Pyruvate
supplementation of a low-cholesterol, low-fat diet: Effects on plasma lipid concentrations and
body composition in hyperlipidemic patients. Am. J. Clin. Nutr. 59: 423-427, 1994.
8. Stanko, R.T., H.R. Reynolds, K.D. Lonchar, and J.E. Arch. Plasma lipid concentrations in
hyperlipidemic patients consuming a high-fat diet supplemented with pyruvate for 6 wk. Am. J.
Clin. Nutr. 56: 950-954, 1992.
9. Stanko, R.T., R.J. Robertson, R.W. Galbreath, J.J. Reilly, Jr., K.D. Greenawalt, and F.L.
Goss. Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone
and pyruvate. J. Appl. Physiol. 69 (5): 1651-1656, 1990.
10. Stanko, R.T., R.J. Robertson, R.J. Spina, J.J. Reilly, Jr., K.D. Greenawalt, and F.L. Goss.
Enhancement of arm exercise endurance capacity with dihydroxyacetone and pyruvate. J. Appl.
Physiol. 68 (1): 119-124, 1990.
11. Stanko, R.T., D.L. Tietze, and J.E. Arch. Body composition, energy utilization, and nitrogen
metabolism with a 4.25-MJ/d low-energy diet supplemented with pyruvate. Am. J. Clin. Nutr. 56:
630-635, 1992.
12. Stanko, R.T., D.L. Tietze, and J.E. Arch. Body composition, energy utilization, and nitrogen
metabolism with a severely restricted diet supplemented with dihydroxyacetone and pyruvate.
Am. J. Clin. Nutr. 55: 771-776, 1992.
13. Stryer, L. Biochemistry. New York, NY: Freeman, 1988.