Updated: Jun 8, 2021
The Posting Picture has little to do with Nitric Oxide elevation for muscle mass but it sure gets your attention.
Original post: April 4, 2011
This poor guy’s distorted perception of figure building has slowly led to disfiguring proportions. NO, nitric oxide supplements wont take you to this unfortunate outcome but it is a good idea to know a little about the strategy since N.O.’s making headlines in therapy and sport today.
When it comes to therapy such as in some cardiovascular conditions, nitric oxide is actually old news; and it’s not cutting edge news when it comes to erectile performance either.
But nitric oxide (NO) has become a hot topic in sports and performance nutrition recently and nowhere have we seen the marketing escalate to more bewildering intensity than in the bodybuilding arena.
There’s no doubt that nitric oxide elevation in certain tissues can have amazing performance enhancing effects but there are some downsides so it may not be all its pumped up to be for everyone.
This discussion will present some basic nitric oxide principles to help users with differing goals make the right choices:
1) Power and Muscle Pump: Understanding a little about the physiological effects and the nitric oxide chemistry may help those who want the most performance potential from their nitric oxide supplements achieve these extremes.
2) Treatment and Prevention of Disease: A simplified understanding of this nitric oxide pharmacology may also shed some light on how the strategy can be used for disease prevention and even treatment.
3) Using NO precursors safely: This insight is also important to those who may be at risk for side-effects from the unmonitored use of the stuff. It may also help explain why some users just can’t tolerate it; or shed light on some physiological effects to help make the link to adverse symptoms for users who shouldn’t be using the NO precursor supplements.
Nitric oxide is synthesized in the body from the amino acid L-arginine through a basic pathway that is enzyme dependent. This means that arginine doesn’t spontaneously convert to nitric oxide; the reaction has to be catalyzed by a highly specific cellular enzyme. In fact, there are three enzyme types located in different tissues that depend on or produce NO. These enzymes have different functions that are not easily controlled in an arginine-loaded environment, creating the need for some safeguards. The three enzymes are:
i) endothelial Nitric Oxide Synthase (eNOS) which works in the blood vessel walls,
ii) inducible NOS (iNOS) which is a central immune system factor, and
iii) neuronal NOS (nNOS) which works to propagate neural activity.
The nitric oxide activity that bodybuilders, power athletes and muscle enthusiasts are in pursuit of is that from eNOS; but what most don’t know is that they are also activating nNOS to assist in muscle contraction intensity. In other words there’s more to NO loading than just blood flow and pump. Proper use of the NO precursors can also enhance contraction intensity and consequently power output.
Endothelial nitric oxide synthase is quite effective at converting circulating arginine into Nitric Oxide. The endothelium is a layer of the blood vessel that houses the eNOS rich cells which produce NO. After it’s produced, this nitric oxide affects the proximate smooth muscle causing it to relax consequently causing the blood vessel to dilate.
The ultimate result of this vessel dilation is increased cavity size, potentially increased blood flow and increased perfusion of blood and the nutrients this blood flow carries into the target tissue. In the bodybuilder’s case the intended target tissue is skeletal muscle and the purpose is to create that bigger, tighter ‘pump’. Fact is, it works, and it works well, that is, if you are healthy and there are no underlying health risks including genetic predispositions for disease.
Nitric oxide elevation does pump up skeletal muscle, and it’s this same system or principle that also pumps up penile tissue tofacilitate erectile function. Arginine is known to improve performance and sensual experience in the bedroom for both men and women. But Arginine supplementation is beneficial at multiple levels when used correctly including blood pressure regulation, growth hormone management, anabolism, recovery from injury and burn trauma; skin and mucosal cell restoration are facilitated by controlled arginine supplementation; and more.
Although, on its own, this amino acid can deliver the described benefits, certain herbs can be used in conjunction with it to direct its activity with greater target tissue specificity. In other words, just taking an oral arginine load on its own delivers non-specific activity that may not produce the intended outcome. Planned and strategic supplementation is key.
Interestingly, impotence, itself is linked to heart disease by way of this common NO pathway. If nitric oxide production is interrupted by way of enzymatic (metabolic) causes or genetic predisposition, there’s a good chance that the same vasoconstriction (or restriction) impairing penile saturation of blood could be impairing blood vessels of the heart reducing blood flow to that muscle as well. Impotence should be considered a preliminary warning for heart disease.
Regular supplementation with functional doses of arginine is a great prophylactic cardiovascular strategy especially if blood clots and and/or occlusions (blood vessel blocks) are a risk factor. But this supplement should be accompanied by herbs like grape seed extract and a few others that support eNOS activity. On the other hand, herbs like red ginsengs, tongkat ali and tribulus terrestris facilitate penile blood saturation from the arginine load.
Here are a few tips to consider:
Side Note recommendation 1 for Cardiovascular Disease: after speaking to your health care practitioner about your type of cardiovascular condition and how these support nutrients may help, consider combining: CoQ10, Natto Kinase, Arginine and Omega 3 Fatty Acids [EPA, DHA])
The research website (www.biologicpharmamedical.com) also presents a Drug-Nutraceutical Interactions Database shedding light on any prescriptive drugs you may be taking and how these interact with these suggestions. Always consult a medical health professional before making amendments to health protocols.
Side Note recommendation 2 for ED: Viagra, (active chemical sildenafil) was originally studied for its effects on the blood vessels supplying the heart. The drug activity was to increase the half-life of NO in these coronary blood vessels by blocking an enzyme (phosphodiesterase or PDE-5) that inhibits NO survival. This would improve blood flow and oxygen availability to the heart muscle.
Viagra is simply a phosphodiesterase inhibitor and without inducing NO directly it simply just allows it to hang around longer to deliver the required blood vessel relaxation and blood flow.
Well, in its trials sildenafil seemed to work better in penile tissues in the initial studies and was successfully marketed as the erectile drug known well today. …which by-the-way, relies in part on arginine for activity. A cautionary note NOT to entertain what you might be thinking now. DO NOTUSE both Viagra and Arginine supplements together – a dangerous prospect that can take blood pressure to dangerous lows.
Some insight on an INSULIN-related NO problem
High dose arginine supplementation supplies the NO precursor throughout the body supplying all of those nitric oxide enzymes with the precursor. The result is non-specific elevation of NO. Research shows that insulin efficiency plays a role in nitric oxide management although the specific pathway is not known. It’s somehow related to an insulin-related influence on NOS enzyme activity rate.
What this means, however, is that someone with a state of insulin resistance may not be able to produce nitric oxide where they want it to be enhanced. Most of us don’t even know we’re contending with a state of insulin resistance unless it has advanced to the clinical level of type II diabetes, where the desensitization to insulin’s signal in peripheral cells of the body is only 65% of the normal activity. This is one pathway linking a common occurrence – the co-morbidity of ED to diabetes. (insulin resistance in relation to prediabetic states and diabetes is discussed in many other articles on this website – search ‘insulin’ for more info)
Research shows that joint degeneration and associated arthritis is associated with an elevated connective tissue nitric oxide level. In other words, inadvertently using arginine precursors (poorly planned formulations) if joint disease is a health concern may further elevate NO in these joint tissues. The mechanics of this adverse activity is related to free radical-induced inflammation (specifically peroxynitrite). It’s also linked to insulin efficiency.
Research shows that as insulin efficiency declines (insulin resistance advances), NO levels in the active chondrocyte tends to increase and oxidative control declines. This translates into a higher risk for joint degeneration and inflammation. In fact, one of the pharmacological actions of the PROPER chondroitin supplementation (research-supported molecular weight) is to ultimately inhibit NO elevation in these worker cells and allow the chondrocyte (the worker cell of the cartilage tissue that utilizes GAGs to rebuild collagen) to do its job undisturbed. Heavy arginine supplementation amidst an antioxidant compromised body, exposed to overexertion, and insulin resistance is a setting for joint degradation and inflammation. The solution is to use properly formulated performance products – no different from using properly formulated high performance engine oils when pushing your sports-mobile to the limit. (more Cutting edge Rsch on this Chondroitin subject matter)
Nitric oxide (NO) is highly reactive and in the presence of the superoxide free radical is quickly converted to peroxynitrite (ONOO – ). This nasty free radical fuels inflammation and is known to damage DNA to kill cells. In fact, it is one fundamental way that our immune system uses NO to protect us from invading pathogens. The problem is, that once this inflammatory cycle starts, it can be self perpetuating turning NO into more ONOO – and intensifying the inflammatory activity in the proximate tissue.
This takes us to another related subject about the oral arginine load and how it can be a problem for those consuming poorly strategized formulations. Supplemented arginine can be used by the immune nitric oxide enzyme (iNOS) of an overactive immune system to over produce the free radical NO > ONOO – ) and start in motion inflammatory activity. For those with autoimmune diseases or other sources of chronic inflammation this arginine dose can exacerbate the condition or even start a reactive cycle of the disease. This includes asthma and COPD.
In fact, a 2005 peer reviewed study hones in on NOS and skeletal muscle inflammation in relation to COPD to demonstrate the global damage beyond respiratory tissues condition and how it relates to the proportional global NOS (throughout the body) induction in the diseased state. Can adding arginine via supplementation add to this inflammatory fire? The answer is a likely yes. The goal of these details is not to ‘bash’ the idea of arginine supplementation rather to highlight the activity.
In doing so, those who may be users of high dose arginine supplementation (>2500 mg per dose for example) and might be experiencing mild signs of escalating inflammation might make the link earlier on rather than later on in the advanced stage of the inflammatory cycle. Insight on these adverse activities is especially important for those with autoimmune diseases, syndromes and chronic inflammation that might be in remission or low activity that could be triggered by these nutraceutical applications.
Once supplemented, we do not have control over how this arginine is used in the body. The activity of nNOS, for example, is critical to nerve impulse transmission but an uncontrollable level of NO in the neurons or brain will lead to higher peroxynitrite levels in these highly vulnerable tissues causing inevitable damage. This can literally kill brain cells by the thousands per second; negatively affecting memory recall, emotional state and general mental health. NO is thought to be central to formation of memory but peroxynitrite is central to neurological decline.
Uncontrolled nitric oxide and the peroxynitrite it breeds can form a cloud of oxidation throughout the body to damage blood vessels, neurons, muscles, eyes and other tissues that are vulnerable to oxidation. No fear though, typically, the body regulates NO well and uses NO for health maintenance. The concern is only for those with underlying disease that sets the stage for poor NO management.
Interestingly, the powerful anti-inflammatory activity conveyed by corticosteroid drugs like prednisone (used to treat the symptoms of autoimmune diseases and chronic inflammation), works in large part by inhibiting Nitric Oxide Synthase, reducing NO concentrations and through this activity, reducing the consequential levels of that highly inflammatory free radical, peroxynitrite. Nitric oxide elevation is definitely a performance enhancement strategy but if health risks are underlying it comes with potential consequence.
Nitric Oxide and the power athlete
Skeletal muscles are intimately affected by nNOS in addition to the more known eNOS activity. The eNOS activity improves bloodflow, pump feel and muscular look. But studies are also now showing that both nNOS and eNOS are expressed directly by skeletal muscle. In other words working muscle is directly involved in producing NOS related activity that literally signals the rest of the body for “MORE blood to this area please”…. BUT also ‘faster stronger nerve signals’ to create stronger contractile force. This is specifically attributed to those fast-twitch muscles involved in explosive power.
The interesting thing to come out of this more recent research is the validation for NOS induction by POWER athletes for improved fast twitch activity. This sets NOS induction strategies in line with sports that involve explosive sprinting, punching, kicking, throwing, jumping, power lifting and more.
However, the vulnerability of the unstable NO as a precursor to that nasty peroxynitrite free radical may make this strategy a poor fit for distance or stamina sports where more free radical loads on the body by not allowing for regular resting periods during the event.
Research also shows that the sex hormones play a central role in NOS expression so anabolic steroid use may play a role in increasing eNOS and nNOS concentration in skeletal muscles and even their activity. This may very well be one of the primary pathways for the performance enhancement by anabolic agents. So for those USING, there may be some significant advantage of high dose arginine co-USE.
Now here’s the interesting paradox.
Exercise is known to induce oxidation (free radicals) as a basic function of the hard work – a consequence of basic oxygen consumption and cellular metabolism. It’s just a natural cellular exhaust like carbon monoxide is exhaust to petro-fuelled automobiles. These free radicals contribute to the conversion of your NO to peroxynitrite to potentially have your arginine load work against you and induce catabolism and tissue damage. So there’s a fine line or threshold dose that crosses over to adversity.
Most of us have biological systems that work efficiently and manage these biological modulators and oxidation safely. But even mild mismanagement can result in lower efficiencies and reduced results from training, supplements nutritional or other.
Recommendation number 1: Supplementing nitric oxide induction strategies for sport or other reasons must be done in the context of proper antioxidant blends that preserve the NO in its functional state, concentrate the conversion activity in the target tissues and reduce the risk of peroxynitrite development.
Recommendation number 2: If inflammatory conditions arise after using an NO inducing supplement lower the dose or don’t use it at all; OR increase antioxidant load to accompany the supplement and combat the ill-effects. (POWERFUL SYNERGISTS – beta alanine is a perfect carnosine-supportive agent for power and building athletes while abundant glutathione supplementation via properly processed undenatured whey supports glutathione antioxidant levels)
Recommendation number 3: If autoimmunity is a challenge do not use NO induction and if you choose to do so use while monitored by a professional AND only use in conjunction with potent antioxidant saturation.
Recommendation number 4: Use of high dose antioxidant supplements even at the best of times improvers NO viability in the body. Grape seed extract is known to actually induce NOS so it may be a good synergist to the program.