Tag Archives: nitric oxide

Interview with Patrick Jacobs PhD

SNI:  Summarize the data briefly regarding the NO or Nitric Oxide category of products. Does it assist with skeletal muscle hypertrophy?

Dr. Jacobs: About 20 years ago, Nitric Oxide (NO) was identified as the factor responsible for increased blood flow to skeletal muscle during exercise. Since then, there have been tremendous efforts to find means to influence NO synthesis for exercise benefits. Increased blood flow should provide increased nutrient supply with improved removal of waste products during and following stressful exercise. These enhancements would presumably increase training capacity and produce increased rates of strength gain or hypertrophy.

The ‘pump’ sought by bodybuilders is primarily an extreme NO-induced swelling of the capillary bed within a muscle in response to intense exercise efforts. Researchers are currently investigating the role of the ‘pump’ as a means to increase internal positive pressure thereby signaling increased protein synthesis and greater rate of hypertrophy.

Today, the NO stimulators make up one of the largest categories of food supplements behind protein powders, energy-weight loss products, and creatine.  Unfortunately, many of the current commercial NO products are based more on advertising hype and less on a scientific basis.

SNI: Arginine is a commonly found amino acid in many supplements. Can it enhance blood flow to skeletal muscles?

Dr. Jacobs: Arginine is the primary ‘active’ ingredient of most NO products. This is based on the well established role of arginine as the precursor of NO. That is, arginine is broken down to make NO. Unfortunately, increasing the amount of a precursor does not necessarily lead to increased synthesis. Delivering more and more concrete blocks to a work site does not speed up the completion of a home as the work process is limited by other factors (workers, mortar). The limiting factor in the synthesis of NO is not the precursor, arginine, but rather the specific enzyme that controls the breakdown of arginine, Nitric Oxide Synthase (NOS).

Advertising claims for arginine based NO products usually reference clinical studies in which high amounts of arginine were injected intravenously producing increased NO production. However, many studies have demonstrated that it is impossible to ingest that amount of arginine (30g) orally as most persons have significant gastric distress with over 7 grams by mouth. This is true regardless of the current fad version of arginine being touted as the next big thing (e.g. arginine AKG, arginine ethyl ester, arginine gobblegook). One further issue to consider is that pre-workout arginine ingestion has been shown to significantly lessen the beneficial GH response to intense exercise.

While arginine supplementation is not a particularly effective means to enhance NO levels, it is possible to influence the production of NO via increased NOS (remember, it’s the rate limiting enzyme) with oral nutritional supplementation. This is actually, to some degree, the basis of common versions of nutrient timing. The most common powerful factor to augment the production of NOS is insulin.  Thus, ingestion of high glycemic carbohydrates produces release of insulin into the blood stream which in turn augments production of NOS. The increased enzymatic activity increases the breakdown of arginine and then production of NO which in turn signals relaxation of arterioles for increased blood flow. This is why uptake of creatine or carnitine is greater when taken with sugar. Insulin sensitivity determines the degree to which tissues respond to insulin with over half of Americans today displaying decreased sensitivity, so this approach today appears limited in application.

A number of nutritional supplements also augment the production of NOS including grape seed extract, pine bark extract, and glycine propionyl l-carnitine (GPLC).

SNI: GPLC – what’s the latest data on this supplement? Does it have ergogenic effects?

Dr. Jacobs: GPLC is a supplement based on a naturally occurring acyl-carnitine. The total carnitine pool is made up of free carnitine and acyl-carnitines, the two most common being acetyl l-carnitine and propionyl l-carnitine. Carnitine is involved in two important metabolic functions: 1) shuttling of free fatty acids into the inner mitochondria where they can be burned for energy, and 2) serving as an anaerobic buffer during intense exercise. However, oral intake has not been shown to effectively increase tissue concentrations thereby limiting effectiveness as a supplement.

The acyl-carnitines present unique characteristics from free carnitine. Acetyl l-carnitine has a very high affinity for nervous tissue and has been shown beneficial in a number of clinical and athletic settings. Propionyl l-carnitine has a very high affinity for skeletal and cardiac muscle tissue and is used as a pharmaceutical agent for persons with cardiac damage and peripheral vascular disease. A variation, glycine propionyl l-carnitine (GPLC) is available as a commercial food supplement ingredient.

Controlled research studies have indicated the high muscular affinity of GPLC is related to its ability to significantly increase NO levels under stress situations, such as intense exercise. My studies illustrated that a single dose increases high intensity exercise work capacity with limited recovery periods. These laboratory tests involved five very intense 10 second cycling sprints with only one minute recovery between sprints. With a single dose of 4.5 gr, there was significantly greater power output and work capacity with significantly lower production of lactate. These results would suggest increased work capacity with many resistance training programs which has been supported by numerous field examinations. Interestingly, our studies also indicated that this same dosage (4.5 g/d) and a lower dose of 3.0 g/d actually produced reductions in power output in the same cycling tests after 30 days of supplementation (worse than baseline placebo). Study participants reported very intense swelling of their thighs (supported by girth measures) that actually limited cycling performance. Another study group receiving 1.5 g/d for the 30 day period displayed improved cycling performance.  Thus, it is possible to get too much of a good thing sometimes and it is important to dose GPLC in regards to your specific purposes.

SNI: What’s the most idiotic thing you ever heard regarding dietary supplements?

Dr. Jacobs: Regularly we hear that dietary supplements are not necessary if we eat a ‘good, balanced diet’. For years, I have asked students, “How many of you ate your 5-8 servings of fruits and vegetables yesterday?” While these students were exercise science majors and presumably promote a healthy lifestyle, less than 10% were able to respond in the affirmative. Thus, we can assume that for most of us, dietary supplements should be considered as a main nutritional staple.

SNI:  For diabetics, is there a supplement cocktail that you would recommend?

Dr. Jacobs: After some thirty years of using high glycemic carbohydrates as part of my nutrient timing strategy, I was diagnosed as a type II diabetic. After following the clinical recommendations provided me for over a year, it became evident why we are losing the battle on diabetes.

The primary characteristic of diabetes is, of course, problems with the digestion and assimilation of carbohydrates, particularly high glycemic carbohydrates. Most Americans ingest a great deal of refined carbohydrates which do provide an energy source as well as making us feel good. However, remember that sugar levels stimulate the pancreas to release insulin and higher levels of blood sugar make the pancreas work harder. Over time the pancreas may wear out and body tissues may become less responsive to insulin. Reduced insulin response limits NO production and the ability of relax the arterioles which become brittle thereby increasing blood pressures (hypertension). Insulin is also known to reduce the activity of the important enzyme responsible for breakdown of fat cells for weight loss.

Effective management of diabetes must be based on very controlled intake of carbohydrates. As Dr. Antonio often states: There are essential amino acids, essential fatty acids but carbohydrates are not essential. Thus, carbohydrates are not as indispensible as generally considered. The two primary functions provided by carbohydrates are as an energy source and as a means to induce vasodilation for increase blood flow. Both of these functions must be provided by alternative strategies if one can be reasonably expected to succeed with a low carbohydrate lifestyle.

First, appropriate fatty acids must be provided as an alternative energy source to carbohydrates. Given that fatty acids can effectively provide long lasting but low intensity energy, what about the need for high intensity energy? There are numerous dietary supplements that provide support for high intensity exercise including creatine, beta alanine, GPLC, etc.

Reduced circulatory function is commonly associated with diabetes. Common dietary supplements known to support healthy circulation included GPLC, alpha lipoic acid, and Vitamin E.

Finally, someone that reads this might respond that these supplements look a lot like what an aspiring athlete might use to enhance their performance. Yeah, this is because the person with diabetes needs to exercise similarly to an aspiring athlete. Exercise is not an occasional complement to your life but rather should be an integral component.


Dr. Patrick Jacobs is the Director/Owner of Superior Performance, a private contract organization.  He holds a PhD from the University of Miami in Exercise Physiology and has achieved Fellow status with the International Society of Sports Nutrition, the National Strength and Conditioning Association, and the American College of Sports Medicine.  Dr. Jacobs has had dozens of peer-reviewed manuscripts published in respected exercise science and rehabilitation journals and has made hundreds of scientific presentations and lectures across five continents. Dr. Jacobs holds patents on several novel forms of exercise equipment. Dr. Jacobs’ background spans both clinical research and practical field application of scientifically based nutritional and exercise programs. His work has examined the benefits of dietary supplements and exercise conditioning in populations ranging from the most elite champion athletes to those persons with chronic disease or disability.  While functioning as a strength and conditioning coach at major US universities, he coordinated the physical conditioning programs multiple national championship football and baseball teams. Dr. Jacobs has also coached elite champions in sports ranging from powerlifting (World record holders) to Indy car racing (Indy 500 winner). He has also assisted with the physiological testing, education, and supervision of many Olympic and Paralympic athletes.  Dr. Jacobs’ diverse research interests have included such topics as specific effects of variations of strength and endurance training, nutritional supplements such as creatine monohydrate and carnitines, cooling vests, functional electrical stimulation, bodyweight supported treadmill training, physiological stresses of auto racing, whole body vibration, and exercise in persons with spinal cord injuries.