Pyruvate for the Treatment of Obesity

March 1999; Volume 2: 31-34

By Dónal P. O’Mathúna, PhD

Have you noticed that your patients’ weights keep climbing? More than half of those 20 and older are overweight, now defined as a body mass index (BMI) of 25-29.9 kg/m2.1 Roughly one quarter of U.S. adults are obese (BMI > 30), as are many children and adolescents.2 Your overweight patients have substantially increased risks of coronary disease, hypertension, type II diabetes, osteoarthritis, cholecystitis, stroke, and sleep apnea. In the words of the World Health Organization, the escalating epidemic is "one of the greatest neglected public health problems of our time."2

Obesity is a complex problem, involving social, behavioral, emotional, cultural, physiological, metabolic, and genetic factors.1 Drug therapy offers some promise, but was set back by the greater-than-previously-reported serious complication rate of fenfluramine, often used in combination with phentermine as "Phen/Fen." Memories of fenfluramine and dexfenfluramine’s market withdrawal, and all those worrisome cardiac ultrasounds in otherwise healthy young women now makes prescription of sibutramine and orlistat just that much less appealing.

Claims

Among alternative approaches, pyruvate is the hottest supplement around. Internet sites proclaim it as the newest and best "fat burner." It is said to boost overall weight loss by 37% and enhance fat loss by 48%.3 Promoters say it lowers cholesterol levels, improves cardiovascular health, and increases athletic endurance. They also claim the support of 25 years of extensive scientific research published in peer-reviewed journals.

So should physicians recommend that overweight patients add pyruvate to their dieting regimens? Not if they look closely at the reported studies.

Pharmacology

Pyruvate (or pyruvic acid) is a metabolite of glucose you encountered in biochemistry as a product of glycolysis. Pyruvate forms an important junction in carbohydrate catabolism, being reduced to lactic acid under anaerobic conditions. Aerobic conditions bring it into the citric acid cycle, allowing its complete oxidation to CO2 and H2O.

Dietary interest in pyruvate began in the late 1970s when animal studies revealed that large quantities of different natural metabolites altered lipid and carbohydrate metabolism.4 Rats raised on ethanol failed to develop fatty liver steatosis when fed pyruvate and/or dihydroxyacetone (DHA). DHA is closely related to another glucose metabolite, DHA-phosphate, and was one of a number of metabolites tested in these studies. Subsequent studies showed that adding pyruvate and DHA to animal diets produced the largest reductions in weight gain and body fat, while increasing heat production and energy expenditure.4

Mechanism of Action

Pyruvate’s mechanism of action in weight loss is unknown. One proposal is based on the reversible conversion of pyruvate to phosphoenolpyruvate, another glucose metabolite. This may be a "futile cycle" where the reaction runs forward and backward, continuously expending energy.5 This theory is supported by the greater heat production and energy expenditure found in animal studies.

Pyruvate also appears to improve glucose uptake by skeletal muscle. Rats fed pyruvate have lower plasma insulin levels, without increased plasma glucose concentrations. Human studies showed that pyruvate and DHA increased glucose extraction by muscles, but plasma insulin levels remained unchanged.6,7

Clinical Studies

Claims that pyruvate suppresses appetite are based on one animal study.4 The authors state that pyruvate’s taste could also account for their observations. A Medline search (using "pyruvate," "weight loss," and "human") revealed four clinical studies, all coordinated by the same researcher, Ronald T. Stanko, MD, at the University of Pittsburgh Medical Center. Three 1998 reviews revealed no additional studies.8,9,10

The first weight-loss study reported by Stanko et al was conducted on 13 obese women (average BMI 38.9 kg/m2; average age 48 years).11 Subjects were confined to bed in a metabolic ward, observed continuously, and allowed no exercise. Participants were randomly divided between two groups, although the number in each group was not reported. All were placed on a severely restricted liquid diet (500 kcal/d) for 21 days, with one group receiving a placebo while the other received pyruvate (26 g) plus DHA (12 g) daily. Those taking pyruvate- DHA showed greater overall weight loss (6.5 kg vs. 5.6 kg; P < 0.05) and greater fat loss (4.3 kg vs. 3.5 kg; P < 0.05).

Stanko’s second study was done with 14 obese women (average BMI 39.9 kg/m2; ages not reported) confined under similar circumstances but given 1,000 kcal/d for 21 days.12 Exactly half the subjects received 30 g pyruvate and showed greater overall weight loss (5.9 kg vs. 4.3 kg; P < 0.05) and greater fat loss (4.0 kg vs. 2.7 kg; P < 0.05), than those who simply endured the diet. Bioelectrical impedance, as in all Stanko’s studies, was used to measure body composition. This study’s conclusion is frequently quoted: "Patients in the pyruvate group increased weight loss by 37% and fat loss by 48%."12

The third Stanko study investigated pyruvate’s ability to reduce cholesterol levels. An earlier Stanko study had shown a 4% reduction in plasma cholesterol while hyperlipidemic patients were maintained at the same weight on a high-cholesterol, high-fat anabolic diet while taking 36-53 g pyruvate.13 In the study of interest here, 34 hyperlipidemic patients (average BMI 28.3 kg/m2; average age 57 years) consumed a low-cholesterol, low-fat diet for six weeks.14 Half the subjects, randomly assigned, received 22-44 g pyruvate daily. Compared to controls who consumed the same diet but no pyruvate, no differences in cholesterol levels were found, in contrast to the results in Ref. 13. However, those taking pyruvate had greater overall weight loss (0.7 kg vs. 0.1 kg; P < 0.05) and greater fat loss (0.5 kg vs. 0.1 kg; P < 0.05).

Stanko’s fourth weight-related study examined whether pyruvate would slow weight gain when a normal diet was resumed after a severely restricted liquid diet.15 Seventeen obese women (average weight 232 lb, average height 63 in; BMI 41.3 kg/m2; average age 43 years) were confined as in Stanko’s first two studies. After 310 kcal/d for 21 days, they were randomized to two groups and everyone received a weight-gaining diet (2,500-2,700 kcal/d) for 21 days. Nine subjects receiving pyruvate (15 g) plus DHA (75 g) gained significantly less weight overall than the eight who received the placebo (1.8 kg vs. 2.9 kg; P < 0.05) and gained less fat (0.8 kg vs. 1.8 kg; P < 0.05). The authors concluded that pyruvate and DHA "will inhibit weight gain by 36% and body fat deposition by 55% during hyperenergetic feeding in obese humans."15

In all these studies, very little additional weight was lost by those taking pyruvate. (See Table 1.) But the small benefits are exaggerated in reports by statistical manipulation. For example, the widely cited 37% great-er weight loss while taking pyruvate was derived from a 3.5 lb difference between the pyruvate and control groups.12 It only seems large when expressed as a percentage. While the results appear statistically significant, their clinical significance is questionable. The reliability of available techniques for measuring such small changes in body composition is also in question, as Stanko acknowledges.15 Further, placing research subjects on a 500 kcal/d diet is highly problematic, not to mention making meaningful comparison with everyday clinical situations difficult.

Table 1
Summary of weight change differences between pyruvate and control groups                                                      
Study
n
Subject Average 
Weight
Diet 
(Cal/d)
No. Days
Dose of Daily Supplements
Differences in
Weight 
Changes*
Differences in 
Body Fat 
Changes*
Ref 11
13
220 lb
500
21
Pyruvate (26 g) + DHA (12 g)
2.0 ± 1.1 lb#
1.8 ± 0.7 lb#
Ref 12
14
237 lb
1000
21
Pyruvate (30 g)
3.5 ± 2.2 lb 
2.9 ± 1.5 lb 
Ref 14
34
232 lb
Weight-based
42
Pyruvate (22-44 g)
1.3 ± 0.9 lb 
0.9 ± 0.7 lb 
Ref 15
17
230 lb
2500-2700
21
Pyruvate (15 g) + DHA (75 g)
2.4 ± 0.9 lb 
2.2 ± 0.9 lb 
*(Average weight loss of test subjects) – (Average weight loss of control subjects) and converted to pounds using 1 kg = 2.20 lb.
#(Average weight gain of control subjects) – (Average weight gain of test subjects) and converted to pounds using 1 kg = 2.20 lb.
_______________________________________________________________________________________________________

Formulation and Dosage

Supplement manufacturers package pyruvate as the bulk powder or as 500 mg capsules, sometimes adding 10 mg DHA. Being anionic, pyruvate is compounded with a variety of cations, usually sodium or calcium. Newer "enhanced" pyruvate products include other supplements like creatine, carnitine, or chromium.

Providers recommend taking 1-5 g pyruvate daily, usually broken into 2-3 doses. Pyruvate can be added to flavored drinks, either by breaking the capsules or using bulk powder. However, these recommended doses remain much lower than the 15-44 g used in animal and clinical trials. The ratio of pyruvate to DHA in commercial products is completely different than in the reported research. Also, the studies used liquid formulations, which could impact absorption, although no bioavailability reports were found. (See Table 2 for price comparison.)

Table 2
Sample pyruvate prices ____________________________________________________________________
Brand Formulation Recommended Dose Price/Count
Pinnacle 1000 mg pyruvate per tablet (calcium and sodium salts of pyruvic acid) 2-6 tablets daily $39.99/60 tablets
Kal 5 g creatine pyruvate per scoop 1 scoop 1-3 times daily $39.98/500 g powder
Twinlab 750 mg calcium pyruvate monohydrate per capsule 3 capsules daily $36.95/60 capsules
Natrol 1000 mg calcium pyruvate per capsule 3 capsules daily $26.99/60 capsules
MET-Rx 500 mg calcium pyruvate per capsule 4 -10 capsules daily $24.95/60 capsules
Natural Balance 500 mg calcium pyruvate per capsule 6-8 capsules daily $19.99/90 capsules
Advanced Research 500 mg calcium pyruvate/100 mcg chromium per capsule 4 caplets daily $19.99/60 caplets

Source: Online mail-order firms
_____________________________________________________________________________________________________

Adverse Effects

All four clinical studies reported pyruvate producing "some" diarrhea, intestinal rumblings, and flatus. Two studies were more specific. Almost half the subjects taking pyruvate (26 g) plus DHA (12 g) had diarrhea and borborygmi,11 while 35% of those taking 22-44 g pyruvate had diarrhea.14 No other adverse effects were reported.

Conclusion

Preliminary studies show that pyruvate provides, at most, a very small benefit to a select group of obese women attempting to lose weight in highly controlled environments. These studies need to be replicated and others performed by different researchers with larger numbers of subjects. No studies have been reported on the commonly recommended doses or on pyruvate’s long-term effectiveness or safety.

Recommendation

Until long-term effectiveness and safety studies are reported, pyruvate should not be recommended as a weight-loss supplement. Pyruvate supplementation as obesity treatment may delay patients from dealing with the complex, difficult problems underlying weight gain.

Dr. O’Mathúna is a Professor of Bioethics and Chemistry at Mt. Carmel College of Nursing, Columbus, OH. He acknowledges Joseph G. Lutz, MD, for valuable input in preparing this article.

References

1. Executive summary of the clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Arch Intern Med 1998;158:1855-1867. Complete report available at http://www.nhlbi.nih.gov/nhlbi/nhlbi.htm.

2. Rippe JM, et al. Obesity as a chronic disease: Modern medical and lifestyle management. J Am Diet Assoc 1998;98(suppl):9-15.

3. Chambliss G. The powers of pyruvate. Healthy Alternatives Newsletter 1998;1. Available at http://www.mineralconnection.com/news5.htm

4. Cortez MY, et al. Effects of pyruvate and dihydroxyacetone consumption on the growth and metabolic state of obese Zucker rats. Am J Clin Nutr 1991;53:847-853.

5. Newsholme EA. A possible metabolic basis for the control of body weight. N Engl J Med 1980;302:400-405.

6. Stanko RT, et al. Enhancement of arm exercise endurance capacity with dihydroxyacetone and pyruvate. J Appl Physiol 1990;68:119-124.

7. Stanko RT, et al. Enhanced leg exercise endurance with a high-carbohydrate diet and dihydroxyacetone and pyruvate. J Appl Physiol 1990;69:1651-1656.

8. Ivy JL. Effect of pyruvate and dihydroxyacetone on metabolism and aerobic endurance capacity. Med Sci Sports Exerc 1998;30:837-843.

9. Sukala WR. Pyruvate: Beyond the marketing hype. Int J Sport Nutr 1998;8:241-249.

10. Canon JP. Pyruvate: Just the facts. Nutr Forum 1998;16:33-34,36.

11. Stanko RT, et al. Body composition, energy utilization, and nitrogen metabolism with a severely restricted diet supplemented with dihydroxyacetone and pyruvate. Am J Clin Nutr 1992;55:771-776.

12. Stanko RT, et al. Body composition, energy utilization, and nitrogen metabolism with a 4.25-MJ/d low-energy diet supplemented with pyruvate. Am J Clin Nutr 1992;56:630-635.

13. Stanko RT, et al. Plasma lipid concentrations in hyperlipidemic patients consuming a high-fat diet supplemented with pyruvate for 6 wk. Am J Clin Nutr 1992;56:950-954.

14. Stanko RT, et al. Pyruvate supplementation of a low-cholesterol, low-fat diet: Effects on plasma lipid concentrations and body composition in hyperlipidemic patients. Am J Clin Nutr 1994;59:423-427.

15. Stanko RT, Arch JE. 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 Relat Metab Disord 1996;20:925-930.