Advice Pool - Health and Fitness

For many years exercise science has perpetuated the concept of a lactate threshold - a point during exercise where a sudden, sharp increase is noted in the concentration of lactate in the blood. This phenomenon is supposedly noticed when blood samples are taken from subjects performing incremental to max exercise tests

According to USFDA, a combination product is one composed of any combination of a drug and device; biological product and device; drug and biological product

much the same as a VO2 max test. Traditionally, it has been noted that when concentration of lactate is plotted against running speed (or %VO2 max) on a graph, as the individual runs faster the quantity of lactate in the blood remains constant up to a certain speed, after which a sudden inflection in the gradient occurs

; or drug, device, and biological product and fixed dose combination would include two or more combinations of drug.

Examples of combination products may in

. This inflection point has been dubbed the lactate threshold - the point during intense exercise where the muscles become increasingly anaerobic, generating vast quantities of lactate. Therefore, this phenomenon has also become known as the anaerobic or ventilation threshold.

As discussed in an earlier article on lact

lude drug-coated devices, drugs packaged with delivery devices in medical kits, and drugs and devices packaged separately but intended to be used together.

ate featured on this website, early exercise scientists (and even some present day ones) attributed the increasing amounts of lactate in the blood during exercise to a lack of oxygen supplied to the muscles. This theory holds that the cardiorespiratory system must be inefficient at matching blood (oxygen) supply to the

here is enormous increase in the number of combination products entering the market in the recent years. Combination products have proven advantages but fixe

muscles and exercise intensity. Therefore, as the intensity of exercise increases, the muscles have to rely increasingly on “oxygen independent” (anaerobic) metabolism and its associated lactate generation. What these researchers failed to understand, or were unaware of was that as the intensity level (power output) of

d dose combinations are still in the process of convincing regulatory authority on their advantages over the single ingredient formulations.

Combination pro

exercise progressively increases, there is a corresponding increase in the dependence of the glycolytic energy system. It is now universally accepted that energy systems are exercise intensity dependent. As explained in the previous article on lactate, this accumulation of lactate is a necessary consequence to maintain

ucts have become life saving products for the pharmaceutical companies who doesn’t have many innovative molecules in their product pipeline and have been inc

the increased flow of energy through the glycolytic pathway.

Tim Noakes at the University of Cape Town, South Africa states that it is highly unlikely that the muscles ever become truly anaerobic. He provides some powerful evidence to back up this statement and quite possibly the most convincing might be what he calls

easingly used in the product life cycle management. Even the companies having product patents are trying to extend their product life cycle through the combi

the “lactate paradox”. In his studies of the results of several research papers on Everest climbing expedition experiments, Noakes noted that lactate accumulation in the blood actually decreased as attitude increased. This finding is the exact opposite of what one would traditionally expect since as altitude increases,

nation products and maximize the revenues. But the companies involved in this practice are overlooking that they are burdening the patients both economically

the ambient barometric pressure decreases, as does the relative availability of oxygen in the inspired air. Therefore, one would suspect that near the peak of Everest, the exercising muscles must be truly anaerobic and generating large amounts of lactate but as mentioned previously, this does not occur. Professor Noakes

and physically. They need to rightly judge the benefits of the combination products and they have to even look at the risks involved when combining the produ

explains that at such an extreme altitude, some internally regulated factor (possibly the brain) severely limits the intensity of exercise to protect the heart therefore also limiting the amount of lactate production. Additional research, has demonstrated that even at rest under more than adequate oxygen availability,

ts. Some of the combination products were well accepted by physicians while others suffered. Companies involved in development of combination products are fi

muscles generate lactate. Furthermore, other researchers have failed to find conclusive evidence that muscles become anaerobic at exercise intensities approaching the lactate threshold or even during maximal exercise. Therefore, Noakes prefers to refer to anaerobic metabolism as “oxygen independent” metabolism since in

ding difficulty in defining their combination products and facing various challenges from selecting a combination to marketing it.

Following aspects would a

his astute opinion there exists no such thing as anaerobic muscle.

Noakes dismisses the probability of a sudden increase in lactate concentration. He explains that if too few blood samples are taken - say for every three or four kilometers per hour increase, then when the rise in lactate is actually observed, it may in

dd to the challenges in developing combination products:

Which markets to tap where the combination products can do fairly well?
Which combination prod

deed show a precipitous “jump” from the one observation to the next. If samples are taken more frequently however, say at every speed increment, then the increase is much more gradual, producing a smoother logarithmic or hyperbolic curve. Dr. Noakes indicates that lactate buildup during increasingly intense exercise is

cts are meaningful and rational?
Which therapeutic categories to select?
Which Combinations can address unmet needs of the patients?
Do combin

the result of its production rate exceeding its clearance. As mentioned in our article,Lactate is NOT the Culprit!, Brook’s lactate shuttle is purported as being responsible for assisting with the transport, utilization and clearance of lactate during ex

tions increase the patient compliance?
What would be the developing cost?
How to tackle the risks encountered during combination product developmen

ercise. At lower exercise intensity levels, the rate of lactate clearance is able to match the rate of production. However, as exercise becomes increasingly more intense and more muscle mass is recruited, proportionately large quantities of lactate are produced, but it is unlikely that clearance via the shuttle will be

t?

As combination products don't fit into the traditional categories of drugs, medical devices, or biological products, the USFDA is in the process of devel

able to maintain pace. Therefore, there exists a speed or intensity level at which the production of lactate surpasses its clearance and the blood concentration begins to steadily increase. This point is what Noakes prefers to call for lack of a better word – the “lactate turnpoint” and that it occurs at an intensity/sp

ping new procedures for reviewing their safety, efficacy and quality.

Professional from academic institutions, pharmaceutical industries, health care indust

eed where the concentration of lactate in the blood is approximately 3.0 mmol/L. If the individual were to run at this constant speed, this would be called running at the subjects “lactate steady state”. In theory this is the fastest speed that can be maintained by the exerciser for extended periods of time such as mara

y and representatives from various regulatory agencies are working out to design the regulatory requirements for manufacture and sale of combination products

thon running.

Therefore, from discussions in this and previous articles, it is safe to conclude that lactate production in the body is the direct result of an increased reliance on the glycolytic energy systems, not from a lack of oxygen in the muscles. Paired with this increased use of oxygen independent metabolism is

.

As there is an increasing trend of the combination products companies manufacturing such products should be able to tackle the problems involved in the de

an increase in lactate production. The sudden jump in lactate production simply does not exist; it increases proportionally with the increased exercise intensity or power output. In addition, it should be obvious that the term anaerobic threshold is a misnomer and that perhaps the only appropriate term to refer to this

elopment. They need to be wiser in analyzing the market trends and the regulatory requirements.

Companies that provide selfless information through particip

phenomenon is the lactate turnpoint.

References and further reading: more information on the concept oxygen independent metabolism and the lactate turnpoint may be found in Lore of Running – a classic book in its fourth edition dedicated not only to running performance, but to cutting edge exercise physiology as well.

tion in industry events and feedback to regulatory authorities would be able to face the challenges and will be successful in developing combination products

HTTP = HTML link (for blogs, profiles,phorums):
<a href="http://www.advicepool.org.ua/article/246002/advicepool-The-Lactate-Threshold--Reality-or-Fallacy.html">The Lactate Threshold - Reality or Fallacy?</a>

BB link (for phorums):
[url=http://www.advicepool.org.ua/article/246002/advicepool-The-Lactate-Threshold--Reality-or-Fallacy.html]The Lactate Threshold - Reality or Fallacy?[/url]

Affiliate Programs Are A Great Way To Make Money Online. They Require Little Investment & Little Risk. But There Are Certain Mistakes That Will Cost You Dearly In Affiliate Marketing. Learn These Mistakes Now.

The more you know the more you save. Get good rates and good coverage with these tips.

Now there are some things that you have to find out about a lawyer if you want him or her to handle the case for you. First you must find out how many cases he has successfully handled till date. If possible talk to people who have used the services of that lawyer and find out how efficient he or she is in handling the case. Well you will surely want the best art lawyer in New York to handle the case for you and of course win the case.

Tags

Links

Advice Pool - The Lactate Threshold - Reality or Fallacy?

Related Articles: