Saturday, April 9, 2011

Sweet Bird of Youth



About a month ago, I took a sabbatical from this blog to view my blogging from a distance. Was I writing useful stuff? Was I helping anyone? Was my blogging centered in people's needs and interests and not merely my attempts to prove I had something to say?

A part of me knows I have something important to say, yet another part of me says that I delight in appearing knowledgeable, smart and sometimes witty. A part of me wants to write for the sake of writing. It's akin to arguing for the sake of arguing. You hear people say all the time, when they interject a hypothetical, "Arguing for the sake of argument."

A little more than a week ago I was introduced to a book that could possibly change my life and perhaps other people's lives.

The book, called "NO More Heart Disease," traces the author's life's work to Alfred Nobel, the inventor of dynamite. Nobel, as almost everyone knows, at the end of the 19th and dawn of the 20th century packaged powdered nitroglycerin mixtures in dynamite sticks that revolutionized modern-day living. Through Nobel's invention, mountainsides have been blasted to make way for roads, mine shafts and tunnels have been built, neighborhoods have been demolished to make way for shopping malls.

Nitroglycerin, invented by a chemist in 1846, is a substance that has been around for more than 150 years. Nothing new with this product, which is even used to treat angina pectoris, or chest and other pains. Exactly how nitroglycerin works to ease the pain was not widely known during Alfred Nobel's time, and that is probably the best explanation for why Nobel himself refused to be treated with nitroglycerin for his cardiovascular disease, even when all other treatments had failed. He died of complications of that disease.

Nobel, against his doctors' advice, refused to use nitroglycerin for his ailment because he did not want a substance used in producing dynamite, or its by-product - nitric oxide, which comes out of automobile tailpipes - to enter his blood stream. To him, nitroglycerin was simply a product for the sewers, not his body.

A Brooklyn boy with a prodigious love for chemistry, Louis Ignarro, was so fascinated by Alfred Nobel's life and dynamite itself that he soon found himself devoting his scholarly energies to a greater understanding of nitroglycerin. His research took him to the study of nitric oxide, which most assuredly comes out of cars' tailpipes but is the primary substance in nitroglycerin that treats angina pectoris.

His interests led him to a career in pharmacology. Through collaborative research with other medical scientists, he learned that there was a silver bullet in the treatment of atherosclerosis - hardening of the arteries - and arteriosclerosis, the clogging up of arteries. It was nitric oxide, but he did not know this at first.

The enormity of the subject transfixed him. It was well-known that the average human body has 80,000 miles end to end of arteries, veins and capillaries. Every cell in the body needs oxygen and nutrients, and the body's infrastructure of arteries, veins and capillaries are the conduit for the blood that oxygenates and feeds the cells in our bodies.

Heart attacks and strokes are the result of blood vessels no longer functioning at optimal levels or are clogged up, depriving organs - especially the heart and brain - of oxygen and nutrients. His life's mission, he felt in his gut, was to find ways to improve the functioning of the blood vessels. His medical research and experiments led him to an amino acid known as L-Arginine. This protein would prove to be effective in repairing the endothelium, the one-cell-thick lining that protects the blood vessels' interior walls.

Ignarro knew that the interior walls had to be protected, otherwise the vessels would harden, a condition known as atherosclerosis. Atherosclerosis or hardened arteries, makes arteries inefficient conduits for blood.

Ignarro knew that the key to delaying, even reversing aging was the proper functioning and health of the blood vessels. In fact, 75% of aging is caused by damaged and worn-down blood vessels.

His research revealed that a substance, which he called "endothelium-derived relaxing factor" or EDRF, was produced by the endothelium and was the body's defense against harmful molecules and substances that damage both the endothelium and the blood vessels' interior walls.

It took years before researchers discovered that the substance was nitric oxide, the very substance found in nitroglycerin and auto exhausts, and which substance the human body produces in sufficient quantities in youth but in ever-decreasing quantities as we age. Nitric oxide, chemical formula NO, or one atom of nitrogen and one atom of oxygen, is secreted by the endothelium in much the same way that the linings in our mouths produce saliva. Nitric oxide protects the endothelium from free radicals and bacteria.

Once this relationship between the health of blood vessels and nitric oxide was established, one would think that it would all be downhill from there. No such luck.

As we age, the endothelium is damaged, veins, arteries and capillaries are blocked all along the 80,000 miles of blood vessels. Because the endothelium is the main source of nitric oxide, not enough NO is produced, and eventually the blood vessels harden to the point that organs no longer get enough sustenance, leading to disease and eventually death.

Ignarro knew that to delay aging and prevent strokes and cardiovascular disease, the key was to keep the blood vessels young and healthy. To accomplish this, the endothelium needed to be repaired.

His research introduced him to an already known protein called L-arginine. That protein was found to repair the endothelium, bringing it back to health and appeared to reverse the hardening of the arteries and other blood vessels. It also appeared to melt away the plaque buildup in arteries, sending the liquefied plaque to the kidneys for disposal.

The problem with L-arginine, however, was that its effect lasted only a few seconds. Hardly the kind of treatment that anyone would be interested in. Through his many experiments he found that L-citrulline, another protein, when combined with L-arginine, worked synergistically with the latter to encourage production of nitric oxide by the endothelium for 24 to 36 hours. This pharmacological breakthrough eventually won for Ignarro the Nobel Prize for Medicine in 1998.

Ignarro was almost home. Since much of the damage to the endothelium is caused by free radicals (oxygen atoms missing one electron) he knew instinctively that the mixture of L-arginine and L-citrulline had to be combined with powerful anti-oxidants to do the job. Determining sufficient quantities of antioxidants was the next big challenge, which Dr. Ignarro was more than equal to.

Ignarro was at Nice (France) airport in 1998 when he retrieved his voice mail and heard his friend in the U.S. tell him that he had won the Nobel Prize for Medicine for his successful research into the cocktail mixture of L-arginine, L-citrulline and antioxidants to combat atherosclerosis and arteriosclerosis. He got the call on April 1, so he assumed that it was an April Fool's joke.

When he arrived at his destination - Naples, Italy - some journalists and photographers greeted him as he alighted from the plane, walking down the metal staircase. He looked behind him because he thought that a celebrity was closely on his trail. There was nobody there.

When his Italian friend, a pharmacology professor, handed him a copy of a press release announcing Dr. Ignarro's Nobel prize, Ignarro fell to his knees on the tarmac, overcome with emotion.

It was as though the decades of hard work and disappointments typical among researchers looking for that proverbial needle in the haystack - all those years of not being taken seriously by the medical community - had melted away. History, of course, is replete with examples of announced breakthroughs that in the end proved to be worthless - even harmful - junk. So how does society know that this time, this discovery is for real? Society only knows after the fact.

The book, "NO More Heart Disease," is a runaway best-seller at amazon.com. It sells for $10.87, with free delivery.

More importantly, the book has encouraged medical researchers to conduct parallel research on the effectiveness of nitric oxide treatment on cardiovascular and other diseases. A brilliant researcher, Dr. Joe Prendergast, has confirmed not only that nitric oxide treats and repairs the endothelium and interior wall of the blood vessels, it also acts as a signaling agent for the maintenance of the vessels.

A substance that is present in dynamite and that comes out of auto tailpipes - nitric oxide - is our own bodies' defense against degenerative diseases of the organs, the blood vessels themselves, cellular damage, and even microbes and other harmful substances that invade the blood stream. In fact, Ignarro and others discovered that our white blood cells repel invaders by producing nitric oxide and using that gas as an important weapon.

And because nitric oxide, through continued and prolonged use and in sufficient quantities, cause normal functioning and regeneration of blood vessels, the effects of disease and aging are known to have been reversed. People who were on the waiting list for heart transplants in the High Desert Heart Institute in Victorville, California (Dr. Prendergast's study and treatment, not Ignarro's) recovered and were taken off the waiting list. Thousands of Dr. Prendergast's diabetes patients recovered from the organ damages that the disease had wrought on those patients.

Because blood vessels tend to become new again when sufficient quantities of nitric oxide are used in treatments, physiological aging stopped for most patients, and in many cases there was evidence that aging was reversed, meaning that people actually got younger.

The excited buzz among the researchers is that because aging is caused primarily by blood vessel decline and because nitric oxide repairs, regenerates, makes supple and softens blood vessels again - to the point that old people eventually become physiologically young again - theoretically people's life expectancy could someday increase to 150 years, instead of today's 79 years.

Has modern medicine found the fountain of youth? I certainly hope so. If man can build robots that think, look, feel and fall in love like humans, why can't man discover a way to doubling his life expectancy?

So far, only man's optimism is eternal. But, in the not-too-far distant future, maybe man himself will be close to being eternal.

(Disclosure: I am involved in the marketing of a product that uses Dr. Ignarro's discoveries to treat cardiovascular, diabetes and other diseases. The product, which increases blood flow as one of its primary effects, also allegedly treats some forms of male impotence. I can't vouch for this personally because this claim is based on theory and not on actual testimony of the product's users.)

3 comments:

  1. From Ramon Franco by email:

    Chay
    Thanks very well written and interesting.
    Ramon

    ReplyDelete
  2. From Gene Pulmano by email:

    Hi Chay,

    You picked my curiosity. I'd like to read the book. We of course in the medical field know of the beneficial effects of NTG and NO. And there is this hypothesis being bandied about, namely, endothelial dysfunction, on the basis of which anti-oxidants have been poised on the public. Alas, the promise of anti-oxidants have not been satisfactorily realized. About one and half or two yrs ago there was a major article published in the New England Journal of Medicine (NEJM), one of the major reputable medical journals in the world based in Boston. The study was about B complex vitamins, including Vit. E, and their effects on atherosclerotic cardiovascular diseases; these vitamins are touted to have anti-oxidant properties. The expectation was that they'd confer benefits with respect to CV diseases. The finding was these did not do any good; in fact, in the particular case of Vit. E, above the dose of 400 units, the opposite seemed to occur, that is, more CV diseases.

    Late last yr I went home to the Philippines because of my brother's illness; he eventually died. Anyway, while passing time in Olongapo, I happened to attend a medical symposium on peripheral arterial diseases at the newly inaugurated hospital, Baypointe Hospital and Medical Center at SBMA in Olongapo/Subic (the location of the old US Naval Base). One of the speakers was Richie Quintos, MD, PhD, who had fellowship at the NIH (USA), did research there and came home to PH, practicing in Manila as vascular surgeon and teaching at UPCM. He talked on peripheral circulation, in particular on microcirculation a cellular and molecular level. I brought up the NEJM article and the unexpected results. I thought I nailed him. But he knew his stuff and up to speed on the latest literature. I wasn't surprised at all. Anyway, his reply was at the micro or cellular level, there is indeed increase flow with some of the antioxidants, but at the macro circulation this is not true; these seem to account for the discrepancy in what is expected for macro-vascular disorders and the results of the study published in the NEJM. This seem to indicate that at the macro level there are some other mechanisms at work. There's the lipid hypothesis and now modified as inflammatory-lipid hypothesis of atherosclerotic CVD. Parenthetically, it turned out that Dr. Quintos is my fraternity brod. I came to know later that he was a TOYM awardee in medicine in the Philippines not too long ago.

    The problem of atherosclerosis is fascinating and complex one. But we're making tremendous progress.

    I'll get a copy of Dr. Ignarro's book. Thanks

    Gene

    ReplyDelete
  3. Hi Gene,

    Thanks for your comments. If you want more information on L-arginine therapy, please google "High Desert Heart Institute L-arginine study" and marvel at how effective this substance appears to be.

    Cesar

    ReplyDelete