Month: October 2017

What Happens to MLB Players Now That The Season Is Over?

“What Happens to MLB Players Now That The Season Is Over? by Greg PryorGreg Royals 1985

What a great World Series!  The great game of baseball and another Fall Classic showed the world why, in my opinion, baseball is the best team sport ever invented.  For most professional baseball players their “cherished” off season is here. A small percentage of players will go to play winter ball in Mexico, Venezuela, Puerto Rico, or the Dominican Republic.  Most players will stay in the States and enjoy their families who they don’t get to see much during the season.

One of the bad things that happens to players on clubs that make the postseason, especially the Indians and the Cubs, is that they will have a much shorter off season. In just 4 short months (exactly 120 days), players on World Series teams will be reporting to spring training.  The “real” MLB ballplayers know that their 2017 season has already begun and they are not wasting time getting ready.

The story of the 2016 MLB World Champs began on the first day of spring training last March at their training site in Arizona.  In reality, the beginning of a baseball season for a “real” MLB player begins on the day that his season ends.  As one who participated in 16 seasons of pro baseball, the 7 month grind of no weekends off and an average of 28 games per month from March to October is not for the feeble minded or physically weak. No offense to the talented players in the NFL, NBA, and NHL who have their own tough grind, but I consider the “combined” mental and physical stress of a MLB season to be the toughest of all sports.  Proper off season preparation by individual players is one of the most important aspects of winning a World Championship.  The story of what George Brett did between the end of the 1984 and the beginning of the 1985 season is a good example.

In 1984, the Kansas City Royals won the American League West Division title but George had one of his worst seasons.  For him, hitting a paltry .284 and driving in only 69 runs was very disappointing and he was challenged by the then-owner, Avron Fogelman, to show people the real Brett in ’85.  George used the off-season to get ready and every Royals fan remembers what happened.  George added 50 points to his average, doubled his RBI output and the Royals went on their first World Series crown.  George put in the workout time during the off season and it paid off.

Next March, around 1,300 pro ballplayers, those on MLB rosters and invitees, will report to the MLB spring training sites of their team.  Older players will be trying to keep their jobs and younger players will be trying to take someone else’s job.  A few will report with jobs locked up because of the size of their contract or the high level of their ability.  Regardless of any of that though, the amount of physical work that they all will have put in over the previous 5 months (but just 4 months for the World Series teams) will determine what kind of season that they, and their teams, will have.

Most MLB players have their own winter workout regimen. The team trainer will give them suggestions and workout schedules to follow but most players will be on their own program.  Many MLB players hire personal trainers to oversee their grueling workouts and to hold them accountable for showing up and putting in the effort.

Being motivated to do effective offseason work is one thing, but the most difficult part of getting ready for another MLB season is to determine what exercises to do, what muscle groups to use, how often to exercise and how many hours or days to rest between exercises.  Every offseason I would try and put on 10-15 lbs of muscle by hiring a trainer to “punish” me during workouts.  I wanted to break my muscles down enough so that they would grow back stronger.  At age 21, I weighed 165 pounds when I signed my first pro contract.  Over my 10 yr. MLB career my weight was between 185-190 lbs. Had I not gotten stronger and quicker, I never would have earned a MLB job.

Another very important aspect of off season conditioning is the diet.  Although MLB players probably eat nutritious meals, I am confident that most use some dietary supplements to help them recover more quickly from workouts.  I did not know until after I was done playing that there are many nutrients not easily found in a decent diet that can have a wonderful effect on muscle recovery after workouts. Some are best used before workouts and some are best used afterwards.

In 1994, my wife and I formed a health and nutrition company called Life Priority, Inc. Life Priority can be located at www.lifepriority.com and offers a line of high quality, results-oriented, scientifically-formulated health supplements to the marketplace.  If you are interested in learning how to get better workouts as a pro player or a weekend warrior, please contact me at customerservice@lifepriority.com.  I will be glad to help evaluate your current regimen and offer time-tested solutions to help you get better results from your workouts.  In 1991, I became a customer of the Life Priority products and, because of my results and the results of others, I joined the health industry.  Make your decision now! The “off season” is shorter than you think!  Get ready for a great 2017!

 

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

Self-Defense Against Infection

Self-Defense Against Infection  By Durk Pearson and Sandy Shaw

First appeared in the July 2008 issue of Life Extension News

Helping Your Immune System Help You

Largely because of FDA regulatory hurdles, life-extension-bookthere are only two new antibiotics in the pipeline and no end in sight for the drought in new antibiotic developments. As a result, antibiotic-resistant infections are becoming a very serious problem, especially so if you have to go to a hospital, where these resistant “bugs” are prevalent. A very close friend of ours died recently from an infection (sepsis) that he got as a result of a catheter implanted in a hospital while being treated for cancer. He never got the chance to benefit (or not) from the cancer treatments. In our opinion, the hospital’s oversight for potential catheter-related infections, a very common occurrence, was very poor, but that is another story. The point we are making here is that you need to avoid infections, and enhancing immune surveillance to prevent them in the first place is what we consider the best strategy.

Rather than just taking supplements that are alleged to “enhance immune activity,” we strive to identify particular types of immune activity that deliver the sort of protection we’re interested in, and we then search the literature for natural substances that can safely provide that type of protection. In the case of infections, we are particularly excited by the protection provided by theanine, isoleucine, and vitamin D. We explain below.

Theanine in Tea Enhances Adaptive Immune Function in Response to Bacteria, Viruses, and Tumors

A new paper in Nutrition Reviews1 reports on the impressive, adaptive immune-enhancing activity of theanine, a unique amino acid found only (as far as is known) in tea (Camellia sinensis). Brewed tea contains millimolar concentrations of theanine.1

Theanine has been found to prime gammadelta T cells, which comprise about 2–5% of total peripheral blood T cells and which mobilize (expanding by up to 50-fold) in response to alkylamines produced by bacteria. Theanine is catabolized in the kidney, resulting in the production of ethylamine, an alkylamine* that primes the gammadelta T cells known as Vgamma2Vdelta2 T cells. Priming does not cause these cells to expand in the absence of antigen but does cause them to more efficiently expand and to produce the potent antimicrobial IFNgamma (interferon gamma) in response to microbial antigens. It is like cocking a gun: the cocking itself doesn’t result in discharge but is a necessary prerequisite for discharge. Consumption of 5–6 cups a day of tea (containing 190 mg of theanine) by human volunteers increased the capacity of Vgamma2Vdelta2 T cells to secrete IFNgamma by up to 15-fold in response to ethylamine or dead bacteria.1 As noted above, the theanine or tea containing it does not increase IFNgamma secretion (which is associated with fever and other flu like symptoms) but primes the T cells to enable them to more efficiently secrete IFNgamma in response to infection.1

*Interestingly, alkylamines are also found in apples and wine and are found in up to millimolar concentrations in urine, breast milk, and amniotic fluid. See Reference 1.

The article reported that severe combined immunodeficient mice reconstituted with human peripheral blood mononuclear cells containing Vgamma2Vdelta2 T cells were protected against death from gram-negative and gram-positive bacteria. Moreover, in the same type of mice, “adoptive transfer of Vgamma2Vdelta2 T cells enhances survival against challenge with a variety of myelomas, carcinomas, and lymphomas. Such enhancement was improved when Vgamma2Vdelta2 cells were first primed.” There are clinical trials in progress testing whether the priming of these cells (by risedronate, a bisphosphonate used to treat osteoporosis, or adoptive transfer of Vgamma2Vdelta2 cells) can effectively treat lymphomas, kidney carcinoma, and solid tumors.

Moreover, a recently published, double-blind, placebo-controlled trial of a proprietary blend of theanine and catechins reported that in healthy human subjects aged 19–70 taking the formulation for three months, the incidence of cold and flu symptoms was decreased by 30%. The authors of Reference 1 found that the protective effect was due to a 30% increase, compared to placebo, in the ability of Vgamma2Vdelta2 T cells to secrete IFNgamma ex vivo (tested outside of the body). (A disclosure, under “conflict of interest” given at the end of this review article, reports that one of the authors owns stock in the company selling the proprietary blend.)

Adaptive Immunity Prevents Growth of Occult Cancer

Another paper2 reports on explicit examinations of the adaptive immune process whereby occult cancers (small, undetectable masses of cancerous cells) are maintained in a small size. In this paper, the authors show that cancer can be prevented from growing beyond a tiny, undetectable size by T cells of the adaptive immune system. Under such conditions of “equilibrium,” loss of immune competence or of the antigenicity (ability of the immune system to recognize the tumor cells) disrupts the process and results in tumor expansion. This is thought to be the reason that some occult cancers emerge when patients have received an organ transplant and immunosuppressive therapy. The authors also propose that suppression by the adaptive immune system may account for why most older men have occult prostate cancers but only in a fraction of them does development of symptomatic prostate cancer occur.

Briefly, the experiments involved exposing mice to a cancer-causing chemical, 3’-methylcholanthrene (MCA), that resulted in the development of sarcomas in some of the mice. They found that “of 187 mice treated with low-dose MCA, 86 (46%) developed progressively growing sarcomas following depletion of CD4/CD8 cells, IFNgamma, and/or IL-12—components that participate in adaptive immunity. . . . We therefore considered the possibility that at least some of the MCA-treated wild-type mice that remained free of progressively growing tumors harboured fully transformed sarcoma cells, the outgrowth of which was immunologically restrained.” In the MCA model, transformed cells emerge exclusively at the site of injection. “Examination of the injection site in 129/SvEv mice treated with 25 µg MCA revealed the presence of small 2–8-mm masses that became palpable within 150 days of MCA injection but did not change in size during an additional 150 days.”

The authors concluded that net tumor cell expansion was being immunologically restrained. They concluded that “maintaining cancer in an equilibrium state may represent a relevant goal of cancer immunotherapy in which augmentation of adaptive tumour immunity could result in improved tumour control” of some kinds of cancers.

The Essential Amino Acid Isoleucine Induces Antimicrobial Peptides in Epithelial Tissues

An exciting paper3 from 2000 that has seemingly been forgotten reported that the essential amino acid isoleucine induces beta-defensins (antimicrobial peptides) in skin, airway, gut, and urogenital tract epithelial tissues, thus providing important protection against microbes by drilling holes in their membranes. “In addition to their direct antimicrobial activities, beta-defensins are chemotactic [attractive] for memory T cells, suggesting that they play an important role in the integration of the innate and acquired [adaptive] immune responses. . . . Isoleucine induced the expression of the beta-defensin 10- to 12-fold with peak activity between 3.12 µg/ml and 12.5 µg/ml.”1

Moreover, the authors found that isoleucine was highly specific in its induction of beta-defensin, as other amino acids did not do so. Isoleucine acts as a signal for the presence of potentially harmful microbes.1 It is an alkylamine1 (as is theanine, see above) and, though they didn’t test for it here, isoleucine probably primes the gammadelta T cells in the same way as theanine. The researchers note that “alkylamines are produced in vitro by a number of pathogenic bacteria includingSalmonella typhimurium, Listeria monocytogenes, and Yersinia enterocolitica.

Vitamin D Against Infections

A recent paper4 reports that bacterial invasion is recognized in injury and stimulates the production of antimicrobial peptides through a vitamin D-dependent mechanism. The authors discovered this via an investigation of the expression of genes influenced by vitamin D3 (1,25D3, the active form) in the setting of wound repair.

They found that “injury triggers a local increase in 1,25D3 signaling in skin.” Then they found that 1,25D3 stimulated an increase in the expression of TLR2 [toll-like receptor 2] and CD14, microbial pattern recognition receptors, and cathelicidin, an antimicrobial peptide.

A somewhat earlier paper5 found that toll-like receptor activation in human macrophages caused an upregulation of the expression of the vitamin D receptor and the vitamin D1-hydroxylase genes that resulted in the induction of the antimicrobial peptide cathelicidin. The cathelicidin killed intracellular Mycobacterium tuberculosis.(The action of the vitamin D receptor in the killing of the tuberculosis microbe links the long-standing knowledge that tuberculosis patients do better when exposed to sunlight.) The authors suggest that innate differences in the ability of human populations to produce vitamin D “may contribute to susceptibility of microbial infections.”

We strive to identify particular types of immune activity that deliver the sort of protection we want, and we then search for natural substances that can safely provide that type of protection.

As part of their study,5 the authors found that “Addition of 1,25D3 to primary human macrophages infected with virulent M. tuberculosis reduced the number of viablebacilli . . . By demonstrating that TLR stimulation of human macrophages induces: (i) the enzyme that catalyzes conversion of 25D3 to active 1,25D3; (ii) the expression of the vitamin D receptor (VDR); and (iii) relevant downstream targets of VDR (including cathelicidin), the present results provide an explanation for the action of vitamin D as a key link between TLR activation and [certain] antibacterial responses in innate immunity.”

Finally, in another report,6 the vitamin D receptor was found to be required for the development of natural killer T cells, which are important cells in immune regulation, tumor surveillance, and host defense against pathogens.

Why Vitamin K Should Be Taken with Vitamin D

We add this section because, while vitamin D and calcium supplements increase the absorption of calcium, adequate vitamin K is essential to ensure that the calcium ends up in bone rather than as calcium deposits in blood vessels. The proper regulation of calcium is carried out by osteocalcin, a hormone like peptide produced by osteoblasts (bone cells that manufacture bone).7 Vitamin K is required for the conversion of the preosteocalcin molecule to osteocalcin, its active form. (In fact, mice with the osteocalcin gene knocked out have abnormally high amounts of visceral fat, and early clinical observations revealed “significantly lower serum OC [osteocalcin] values in patients suffering from type 2 diabetes compared to healthy persons, and restoration of glycemic control resulted in increased OC levels.”7

While the recommended daily allowance of vitamin K is 1 µg/kg of body weight per day, that is based only upon adequate levels for proper blood clotting and not on the amount required for optimal bone formation or to prevent calcium deposition in blood vessels by carboxylating osteocalcin. “There is some evidence that the current RDA may not be sufficient to maximally carboxylate [activate] this protein [osteocalcin].”7 Most dietary vitamin K comes from a few leafy green vegetables and four vegetable oils (soybean, cottonseed, canola, and olive); however, the bioavailability from vegetables is relatively poor. “The 2005 Dietary Guidelines for Americans recommends 3 cups/week of dark green vegetables, which contain about 100 to 570 µg/serving of vitamin K.”8 However, what is actually absorbed is unclear and likely to be much less.

Studies such as that of Sokoll et al.9 found that increasing vitamin K intake from 100 to 420 µg/day resulted in a significant decline in the percentage of uncarboxylated osteocalcin within five days, suggesting that the “normal” intake of vitamin K in the North American population is not sufficient to maximally carboxylate osteocalcin.

References

  1. Bukowski and Percival. L-Theanine intervention enhances human gammadelta T lymphocyte function. Nutr Rev 66(2):96-102 (2007).
  2. Koebel et al. Adaptive immunity maintains occult cancer in an equilibrium state.Nature 450:903-6 (2007); also see commentary on this paper in same issue.
  3. Fehibaum et al. An essential amino acid induces epithelial beta-defensin expression. Proc Natl Acad Sci USA 97(23):12723-8 (2000).
  4. Schauber et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 117(3):803-11 (2007).
  5. Liu et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311(5768):1770-3 (2006).
  6. Yu and Cantorna. The vitamin D receptor is required for iNKT cell development.Proc Natl Acad Sci USA 105(13):5207-12 (2008).
  7. Booth and Suttle. Dietary intake and adequacy of vitamin K. J Nutr 128: 785-8 (1998).
  8. Johnson. Influence of vitamin K on anticoagulant therapy depends on vitamin K status and the source and chemical forms of vitamin K. Nutr Rev 63(3):91-7 (2005).
  9. Sokoll et al. Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects. Am J Clin Nutr 65:779-84 (1997).

©2008 by Durk Pearson & Sandy Shaw

Life Priority is proud to have a working relationship with Durk Pearson and Sandy Shaw since 1994. We offer many of the Pearson & Shaw Designer Food formulas.

Life Priority Inc. 11184 Antioch # 417  Overland Park, Ks. 66210

 800-787-5438      www.lifepriority.com

 

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

Arginine and Muscle Memory- The “Fountain of Youth?” (Interview with Life Extension Scientists: Durk Pearson & Sandy Shaw)

Life Priority Presents— Durk Pearson and Sandy Shaw’s   MUSCLE MEMORY

Dear Customer:

One of the most valuable products offered by Life   Priority, Muscle Memory, has been described as “Youth in a Bottle”   by the formulators, Durk Pearson and Sandy Shaw. When you use it consistently   before workouts or at bedtime (on an empty stomach), you will experience why   this could be your personal fountain of youth.

The enclosed interview will describe the value of using   Muscle Memory. In 1991, I began using this formula to increase my strength   and endurance, speed up my recovery time, and have less soreness after   exercise. The use of Muscle Memory allows you to get the most from your   exercise.

For optimum results, use 1-3 servings of Muscle Memory 1   hour before exercise on an empty stomach (avoid eating protein 2-3 hours   before work outs) or 1 hour before bedtime. Read label instructions before   using Muscle Memory.

Here’s to the Retention of the Youth that is still in   you!

Greg Pryor, President Life Priority

____________________________________________________________________

Interview on Muscle Memory with scientists   Durk Pearson and Sandy Shaw–

Greg: Durk and Sandy, our customers   want to know about the Muscle Memory. Would you explain the formula to our customers   and the reasons why you created it? What is growth hormone and how important   is it to keep our bodies supplied with nutrients that increase the release of   gro

wth hormone?

Durk: Sure Greg, our interest in growth   hormone and it’s history goes back a long, long way, to the early ’70s, when   we realized that not everything associated with aging was necessarily caused   by free radicals and that corrective treatments could go beyond controlling   free radicals. Sandy and I became concerned about changes in the neuroendocrine   system that occurred with aging. For example, as a woman gets older, one of   the obvious changes is menopause. In males, there is a reduction in   testosterone. Some of these changes are in response to internal   “clocks”; others may be due to random damage, possibly related to   free radicals, possibly related to something else, such as receptor loss or   down-regulation. One of the most striking changes we noticed was the loss of   immune system function with age. A person at age 70 is lucky to have 20% of   their T-cell function left compared with when they were a young adult. That’s   why pneumonia used to be called “the old man’s friend.” That is,   pneumonia would kill you over a period of a few days; whereas something like   cancer would kill you over a period of a year, much more miserably.

Sandy: A case of viral pneumonia might   not even stop an otherwise healthy young person from going to work- just make   them miserable for a while- and certainly would never put them in the   hospital. The same virus could easily kill somebody in their 70’s.

Durk: We also noted that as you get   older you start putting on more and more body fat and it becomes harder and   harder to put on lean body mass. A potentially disastrous occurrence is the   fact that it takes longer and longer for wounds to heal. A wound that would   have healed in 5 weeks when you were in your teens or early 20’s might not   heal for 5 months when you’re in your 70’s.

Sandy: What we figured out is that all of   these changes were consistent with a reduction in the release of human growth   hormone.

Durk: Growth hormone (GH) doesn’t make   a person grow any taller after they’ve gone through puberty. You just don’t   grow any taller after that. However, during our mid-20’s to 30 or so, there’s   a big drop in GH output. And that’s when a person begins to find it much more   difficult to put on lean body mass by exercising. For example, if a person in   their teens or early 20’s does heavy exercise, they will release a relatively   large amount of GH from their pituitary. Or if they’re injured, they’ll also   release GH. By the time they’re in their 40’s, it takes a heck of an injury   to get a good GH release, and exercise will rarely do it anymore.

Sandy: It is possible to improve the   response of the GH-releasing system through the use of nutrients, and that’s   something that we became interested in during the 1970’s.

Durk: About 1976 we came to the   conclusion that it was quite possible that a reduction in GH was responsible   for many of the problems of aging, and we got a private grant to do   literature research on this. In fact, the private granting foundation asked   the person who won the Nobel Prize for sequencing human growth hormone   whether he thought our idea had any merit. He said, “Yes, this sounds   interesting. Let’s hope they follow up on it.”

So, as we proceeded to read more about   it, the more interesting it looked. Our thoughts turned to how you get GH   released, because actual human GH was very difficult to come by. Since then,   recombinant human GH has made the hormone much more available, although it’s   still very expensive.

Sandy: So what we did then was to look for   various substances that would cause release of endogenous GH, and we found   out that there were quite a few. For example, some of the opiates will do it,   but for obvious reasons that wasn’t really a suitable source.

Durk: We found out that there were   certain drugs that would do it, for example, L-dopa. But it’s highly   experimental for those who don’t have Parkinson’s disease to take L-dopa   every day for the rest of their lives. What we finally found is that amino   acids release GH, and some do it much better than others. In particular,   different amino acids had different ratios of insulin release to GH release.   Our goal was to find one that would maximize GH release and minimize insulin   release. Arginine and ornithine both fit that criterion.

We decided to use arginine for two   reasons. (Although ornithine was twice as powerful as arginine on a   gram-for-gram basis, it costs twice as much.) The first reason was that you   have a minute amount of ornithine in your diet, whereas you have substantial   amounts of arginine.

Sandy: Ornithine isn’t used to make   proteins.

Durk: You make proteins that contain   arginine. And as a result, we thought the choice of arginine would be more   conservative with respect to what human metabolism is adapted to. Also, we   found out that 20 grams of arginine is normally used intravenously as a   provocative test for GH release to see if a person’s pituitary is responding   normally. We wanted to find out whether oral doses were also capable of doing   that.

It turned out that oral arginine was   particularly effective at releasing GH when you add a couple of additional   factors to it, choline and vitamin B5 (pantothenate). That’s because GH   release involves the cholinergic nervous system.

Arginine along with choline and B5   works just fine when taken orally as long as you don’t have a lot of other   proteins in your stomach breaking down into amino acids that compete with   arginine’s entry into the brain. It worked even better than we had expected.

Sandy was the first experimental subject   matter for this treatment. We were at a Gordon research conference on the   biology of aging back in 1979. And Sandy   jumped up to try to get something off a shelf in our room, and when she came   back down she didn’t come down on her foot straight and there was this   horrible cracking sound.

Sandy: I noticed that my foot was swelling   up, and it was very tender and I couldn’t walk on it very well. I had to   hobble around.

Durk: In fact, it was Dr. Denham   Harman, the father of the free-radical theory of aging, who diagnosed her as   having a probable broken foot and suggested she get it X-rayed.

Sandy: Which I did, and it was broken. We   were aware of studies on animals with broken bones that healed faster with an   arginine supplement. And so we thought, “Well, we’ve done enough   literature search on this; time to start taking it.” The arginine growth   hormone release should help to speed up the healing.

Durk: Because she wasn’t moving around   nearly as much, she thought she ought to do some exercise, so she did some   bench presses lying on her back, which didn’t put any load on her foot. I   knew how much weight she was lifting, and I measured how far she lifted it   and counted the number of times she did it- she spent about 3 minutes a day   on it- and, by golly, in 5 weeks she lost about 20 pounds of fat and put on   about 5 pounds of lean body mass. Arnold Schwarzenegger in “The   Education of a Bodybuilder” said it would be difficult for a dedicated   male bodybuilder to accomplish that much gain in a year.

Also, the foot seemed to be completely   healed up a lot sooner than we expected. The doctor said it would be 2 or 3   months before she was really able to walk around on it. Yet in 5 weeks she   felt fine, had it X-rayed, and it was okay. I mean, it wasn’t broken anymore;   not only that, in the X-ray it didn’t look like it had ever been broken.

Another very interesting story involves   a friend of ours, a plump, sedentary, gourmet, 72 years old, who fell down on   an icy sidewalk several years ago and broke his arm. This guy is very   sedentary. His idea of exercise is taking the elevator from his condominium   down to the underground parking garage, underneath his law office and taking   the elevator up to his office.

His doctor told him that in about 5   months he would probably have to do bone grafts because he didn’t think it   would heal, given our friend’s age and condition. Well, our friend called us   up and said “Didn’t you once tell me something about accelerated wound   healing?” He asked the doctor about that and the doctor was very   dogmatic. “No, it’s not possible to speed up wound healing, there’s   nothing that can be done about it.” So he called us back and we told him   about Muscle Memory our formulation of arginine, choline, and B5, and sent   him some samples. He started taking three servings when he went to bed at   night. Five weeks later he felt so good, he went back to the doctor and said,   “I want you to take the cast off.” The doctor got a real snicker out   of that.

Sandy: He thought it was simply ridiculous.   But the patient asked for it, so he took another X-ray.

Durk: The doctor was absolutely   dumbfounded when he looked at the X-ray. It looked as though the bone had   never been broken, there was not shadow on it indicating a fracture and the   bone was a full density.

If a 12 year-old breaks an arm, you can   take the cast off at 5 weeks. But if you X-ray it, the bone is not going to   be at full density. Here, you have a guy who’s 72 years old with full density   at 5 weeks! In fact, the doctor said that if he hadn’t personally taken the   original X-ray, personally taken the second X-ray, and personally set that   arm and put it in a cast, he’d call it some type of insurance scam, because   what he saw was “completely impossible.”

We’ve heard of this sort of thing   happening to a lot of people using our arginine, choline and B5 combination,   like bodybuilders and Olympic athletes and so forth, who have also found out   how useful this is. It really helps a lot in maintaining the ability to gain   strength from peak output exercise. It also seems to help improve skin   elasticity. A lot of people who’ve been taking it for a year or so notice   that their skin, particularly on their face and neck, stays nice and tight.   And that’s because GH causes the liver to release IGF-1, which in turn   up-regulates production of elastin in the skin and also, I might add, in the   arteries. Elastin’s the molecule that makes tissue all nice and springy and   elastic. Anybody who has seen the skin pinch test done on the back of my own   hands can see that it’s really much more elastic than you would expect for   someone who’s 54 years old. We’ve been taking this formulation since 1979 now   -18 years – which is a pretty significant fraction of our adult lifetimes.

Durk: Remember, there are various   things that can limit your life span and also your quality of life. One thing   is simply muscular strength. A lot of elderly people end up falling down,   breaking their hips and then dying within the next year, because they never   really recover. Such falls have been traced in some cases to the loss of   equilibrium due to damage to the inner ear. But in most cases it’s thought to   be due to lack of muscular strength. A person who stumbles can usually right   himself but if you don’t have enough muscular strength, down you go. This   seems to be a major problem. The average woman over 65, I believe, cannot   lift 10 pounds.

Sandy: That’s right. It’s pretty shocking.

Durk: When you consider that a gallon   just of milk weighs about 9 pounds, you realize what a big limitation that   is. Another thing GH does is help maintain the function of T-cells in the   immune system. The heart of that is the thymus, where T-cells are produced,   selected, and educated or programmed. Maintaining GH levels can help retain   thymus function and thymus mass.

Maintaining elasticity goes beyond the   production of elastin. One very important thing about arginine is that it is   a very powerful sacrificial target for cross-linkers. If nothing else gets   you, you’re going to end up having to go on kidney dialysis at the age of 90   or 100 or 120, because, throughout your lifetime, cross-linking reactions are   taking place in the collagen in the basement membrane of your kidneys.

Sandy: As a result of glycosylation, this   causes the kidney’s basement membranes to thicken throughout life, and   eventually it becomes thick enough that it is not filtering the serum well at   all. In people who have diabetes, the process is accelerated. Diabetics   usually die of kidney failure. There was a very exciting study in diabetic   mice that were given arginine to what would be – scaled up to a human dose –   about 3 gm of arginine a day. They found that the mice that received the   arginine had normal kidneys when they became old as compared with controls.   The diabetic mice that did not receive arginine were dying of kidney failure.   They had thickened basement membranes in their kidneys.

Durk: In fact, what they found was that   there was no increase in thickness after about 6 months in the basement   membranes of those mice that got the arginine. It entirely abolished that   age-related increase in basement membrane thickness and cross-linkage.

Sandy: It’s interesting to note, too, that   the tests also have a basement membrane that thickens throughout life.

Durk: In some cases GH can block the   effects of insulin. And a person who has type II diabetes is already insulin   resistant. You don’t want to make them anymore insulin resistant. In fact, we   have found that in a small percentage of type II diabetics, the blood sugar   will go sky high if they take Muscle Memory. With most others, that doesn’t   happen. In fact, gradually increasing the doses of Muscle Memory may result   in an increased insulin sensitivity and a decrease in blood sugar levels.   However, this is something that has to be done under a doctor’s supervision,   where they’re actually measuring your blood sugar response as you go from   perhaps half of one serving of the nutrients to start and gradually work your   way up.

Sandy: That’s why we recommend on the label   that diabetics not use the product.

Durk: Let me also mention another   precaution: Arginine can increase the rate of growth of all tissues and that   includes, potentially, cancerous tissues. If cancer already exists, it might   accelerate its growth.

Sandy: I was reading in one paper about   breast cancer and GH. The authors found an improvement in the immune response   to the tumor in those patients taking GH, but, at the same time, the tumor   was getting assistance in growing, because growth factors – any growth   factors – do exactly that: improve growth.

Durk: Right. If a person has cancer,   they do not want to take this. If they’ve had cancer, and their doctor says,   “We got it all, there’s none left,” then there’s no reason that   they shouldn’t be able to take it.

Sandy: But caution is always the byword. I   think that by now your customers know that the two of us are extremely   conservative. We try to take as few risks as we possibly can and hope that   will contribute to our being able to live a very long time.

Durk: Another interesting thing I’ve   discovered: I’m pretty doggone sedentary; I spend most of my time lying on my   waterbed or a lounge chair reading scientific journals. But sometimes I go   out and do some very vigorous things like digging post holes or carting   concrete sacks around or branding cattle or digging out a hot spring. Believe   me, shoveling mud is a very, very backbreaking task. I find that if I don’t   take Muscle Memory before I do that, I will have aches and pains starting the   next day that’ll be really bad and will last several days.

Sandy: How achy were you after the cattle   branding?

Durk: Not at all because I was sopping   up Muscle Memory all day; over the day I took about three servings of Muscle   Memory spread out over the day. I just mixed it up in a drink and put it in   the cooler.

Durk: For GH release, you need to take   it all at once: two servings for a woman or three for a man, preferably at   bedtime, because about an hour and a half after you go to sleep is your   biggest GH release if you’re past, say, your mid 20’s. Or, alternatively,   about 3/4 of an hour before you engage in heavy peak-output exercise. But in   the cases of branding or digging out a hot spring, I’m usually at it all day   long. So I take about three servings, put it in some ice water, and stick it   in the cooler. I usually mix it with a couple of servings of Lift as well. I   just drink that throughout the day. No aches and pains that day. No aches and   pains the next day or the day after.

Durk: Basically what you want is to   mimic, as far as possible, the natural pulsatile release. What you don’t want   to do is to have elevated levels of GH all the time.

Sandy: Which is what you get with GH   infusions or even subcutaneous injections of GH that they’re giving elderly   people. These are not like the physiological releases of growth hormone.

Durk: GH is supposed to be released in   pulses, like insulin, and a continuous high level results in a resistance to   GH and all sorts of problems downstream from that. Now when you’re sipping   three servings over a period of maybe 6 hours of heavy work throughout the   day, you’re not going to get any GH release effect, but you will get the   beneficial effects of the arginine-derived nitric oxide.

Sandy: There have been a number of studies   of arginine with respect to atherosclerosis, particularly in animal models   like rabbits. The first sign you see before you see any fatty streaks or any   other visible evidence of atherosclerosis is that the arteries fail to dilate   in response to acetylcholine. That can be reversed by infusing arginine.

Durk: Instantly reversed! Twenty   seconds after you bathe the rabbits artery with the arginine, you’ve reversed   that resistance and normalized the response of the arteries so they dilate.

We know of one case where that happened   in a human. Our 72-year-old friend, after his arm healed up so fast, called   up and said, “Would it hurt me to continue taking this stuff? It really   makes me feel good, and it sure healed me up. I think this is doing a lot of good   for me.” He wasn’t a diabetic, so we said, “Well, we’ve been taking   it for 10 years now, go right ahead and do it.”

Sandy: So he started doing that. About a   year and a half later, he had a fast-synchronized MRI scan of his brain,   which gives very fine pictures of the cerebral arteries. He said that the   doctor that did this, a different doctor from the one who fixed his arm, was   absolutely astounded because, of his three major cerebral arteries, two of   them were completely clear, and one of them had about a 20% obstruction,   which is about the bottom end of the ability of this technique to measure at   that time. The doctor asked him what sort of diet he was on – was he a   vegetarian? Was he on a Pritikin diet, or what? And he said, “Well, my   diet was bacon and eggs every breakfast.” And that’s just about true;   those are the sort of things he eats. He’d be better off if he ate a lot more   veggies, but that isn’t what he eats.

Sandy: We don’t know what his arteries   looked like before he started using the arginine supplement, but the end   result is certainly consistent with what the experimental studies have shown   with arginine.

Arginine has also been studied for its   effects on blood pressure. Part of the blood pressure regulation process is   the arteries being able to dilate under the control of the cholinergic   nervous system.

Durk: And this is mediated by nitric   oxide. The scientist who figured that out won the Nobel Prize for it.

Sandy: A lot of people who have high blood   pressure, especially associated with atherosclerosis, have a failure of their   nitric oxide artery dilation system, and arginine often can help reverse   that.

Durk: We’ve been told that, under a   physician’s supervision, some people have been able to reduce their doses of   anti-hypertensive medication by taking Muscle Memory throughout the day. Some   people have even been able to discontinue the drugs entirely, particularly if   they add potassium and magnesium along with an arginine, choline and B5   supplement throughout the day. But this should be done only under a   physician’s supervision.

Sandy: One other thing to keep in mind is   that using nutrients to get GH release is a very different thing from using   the hormone itself, from the point of view of the feedback controls that   regulate the release of hormones in the pituitary and elsewhere. When you   take growth hormone itself, you bypass the normal regulatory features that   control when the hormone is released and how much is released. You put GH in   there, and you just override those controls. When you take arginine and   choline and B5, you still have all of those regulatory mechanisms in place to   control how much is released and when its released.

Durk: Another thing that we definitely   don’t want to forget is that the mechanism that causes erections in male   mammals is, in fact, nitric oxide. That’s what causes the vasodilation that   results in the corpus cavernosa engorgement with blood producing an erection.   If you take Muscle Memory 30-45 minutes before sex, you’re likely to notice   the difference. There’s similar erectile tissue in women inside the lining of   the vagina.

Sandy: Just like the arteries that we talked   about earlier in the development of artherosclerosis, the cholinergic   mechanisms are also involved in the dilation of the blood vessels to the penis.

Durk: I’m not at all surprised that   occurs.

Durk: I think that Muscle Memory does a   lot to make your neuroendocrine system look younger. In fact, the mixture was   used in a double-blind, placebo-controlled study at a private fertility   clinic. They took women who were not ovulating and put them on pergodile,   which is a dopaminergic agonist, FDA-approved for fertility purposes (as well   as for treating Parkinson’s patients). Most of them ovulated after they’d   been on Pergodile for a while. The ones that had failed to ovulate after 6   months were put on two servings of the arginine-choline-B5 mixture at bedtime   every night in addition to Pergodile.

The doctor said that the results were   absolutely amazing: 80% of the women ovulated within days of going on the   mixture. He said it was like turning on a light switch. I might add that one   woman was about 1 and a half years postmenopausal; another one was about 2   and a half years postmenopausal. So, in a lot of ways, Muscle Memory makes   your endocrine system look like that of a younger person.

Durk: Yes, in fact, it can. We reported   that over a decade ago in one of our Life Extension books. A few hundred   milligrams of buffered niacin can indeed do that; that’s what I take at   bedtime along with my Muscle Memory. About 200 mg of niacin will give you   double or triple the GH level compared with backgrounds. This is significant,   but it’s nowhere near as big a pulse as you would likely get with the   arginine-choline-B5 in Muscle Memory.

Durk: You would typically get one   several times as big as with the niacin alone.

Durk: I use it myself whenever I have   to learn some sort of new motor type-task. Also, we have had some interesting   comments from various people. We know a retired professional golfer in his   sixties who, over a period of about 5 weeks, took five strokes off his game.   Normally at his age – he’d been playing at least a few times a week for 20   years – you’re not going to get better; you’re just going to get worse with   the passage of time. And that’s what he said; his game had gradually been   getting worse over the years. Taking five strokes off in 5 weeks is not   something that normally happens. But it’s been found that nitric oxide   release is absolutely essential for motor learning in the cerebellum, and it   also appears to be necessary for long-term potentiation in the brain, which   is the mechanism that’s involved in long-term memory. And I think that   explains his success.

Durk: When you go over it all, it   really sounds like too much of a panacea to be real. As the years have gone   on we’ve found more and more delightful things about arginine.

Durk: I’ll tell you this; if you’re   full of anabolic steroids to the point where you’ve down-regulated your   anabolic steroid receptors, the dietary supplement might conceivably not   work. Another possibility is that people who abuse GH by injecting it,   subcutaneously or intramuscularly, are definitely going to develop resistance   to it because it’s not being given in the pulsatile manner. Moreover the   doses of many GH releasers are inadequate, and most formulations lack   adequate choline and B5.

Sandy: Another thing is that, people who are   restricting their calorie intake significantly are going to be less likely to   release growth hormone because, under the conditions of fasting or caloric   restriction, animals go into a state where they do not grow. They reserve the   energy that they’re getting for more important things, like maintenance.   Growth is not a priority when you’re getting a restricted amount of energy   intake. So, for people who are on a diet that’s low enough, they may not get   a growth hormone release.

Durk: Also, if a person takes a big   slug of protein supplement, like 50 gm of protein, along with their Muscle   Memory, not much of that arginine is going to get to the brain compared with   taking it on an empty stomach. I’m afraid that a lot of body-builders may be   taking a protein supplement along with Muscle Memory before exercising. What   they should do is take the Muscle Memory before the exercise and take the   protein afterwards.

Muscle MemoryTM was designed by Life Extension scientists Durk Pearson   & Sandy Shaw for their own use.

Durk Pearson and Sandy Shaw were among the first scientists, beginning more   that 15 years ago, to recommend that people take arginine supplements
(along with choline and B-5) to boost their natural GH release and thereby   achieve a variety of life-extending benefits, including building lean muscle   mass
(in preference to fat), accelerating wound healing, strengthening bones,   improving immunity, and enhancing skin flexibility.

Muscle MemoryTM has been a Life Priority classic since 1994, for more   than a decade for:

  • People who recognize that the ingredients in        Muscle MemoryTM help accelerate physical fitness.
  • Those interested in the role of nutrition in        biological aging.       Muscle MemoryTM helps trigger your own internal biochemical        resources of mental and physical power for enhanced vitality and        youthfulness.
  • Store in a cool, dry, dark place.

SUGGESTED USE: Read the directions on the bottle   before consuming.
Use 1-3 tablespoons 45 minutes before work-outs (on an empty   stomach) or take 1-3 tablespoons of 1 hour before bedtime.

Order Muscle MemoryTM now!

 

www.lifepriority.com.

© Copyright LIFE PRIORITY

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

In the News: Women’s Dementia Worsens Faster Than Men’s

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 4 • August 2015

In the News: Women’s Dementia Worsens Faster Than Men’s

So says a headline in the July 22, 2015 The Wall Street Journal. According to the study (398 subjects who participated in the Alzheimer’s Disease Neuroimaging Initiative), women’s cognitive decline took place about twice as fast as men’s. The good news is that it is very likely, based on scientific studies showing that women need more choline than men do (Fischer, 2007), and that, as choline has been identified as a nutrient important to cognition (Poly, 2011) a deficiency of choline is one cause of this vulnerability to dementia in women. Not only does estrogen play an important role in the cholinergic nervous system (Fischer, 2007, Craig, 2010)—estrogen that declines rapidly following menopause—but it is known that in older people, choline is taken up less effectively into the brain (Cohen, 1995). In addition, women are much more susceptible to autoimmune diseases than men are and the cholinergic nervous system is a major antiinflammatory system (Tracey, 2007).

Add it all up and the evidence points to a need for additional choline in older women. The amount of choline recommended by the Institute of Medicine (IOM) for non-pregnant women, 425 mg a day, is (in our judgment) too low to supply adequate amounts of choline to older women when you consider the reduced ability to transport choline into the brain, the loss of estrogen, and also the variation (dietary composition (van Wijk, 2012), choline consumption, genetic and epigenetic differences in the ability to absorb choline from the diet, get it into the brain, and then convert it to phospatidylcholine via biochemical pathways) between individuals suggests that the amount that may be adequate for much of the population per the IOM recommendation may not be adequate for YOU.

In short, choline is a major nutrient for keeping your cognitive function in good condition as you get older. We ourselves take 2 grams a day of choline in the form of choline dihydrogen citrate.

References

  • Fischer, daCosta, Kwock, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr.85(5):1275-85 (2007).
  • Poly, Massaro, Seshadri, et al. The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. Am J Clin Nutr. 94:1584-91 (2011).
  • Craig, Brammer, Maki, et al. The interactive effect of acute ovarian suppression and the cholinergic system on visuospatial working memory in young women.35:987-1000 (2010).
  • Cohen, Renshaw, Stoll, et al. Decreased brain choline uptake in older adults. An in vivo proton magnetic resonance spectroscopy study. 274(11):902-7 (1995).
  • Physiology and immunology of the cholinergic antiinflammatory pathway.J Clin Invest.117(2):289-96 (2007).
  • van Wijk, Watkins, Bohlke, et al. Plasma choline concentration varies with different dietary levels of vitamins B6, B12and folic acid in rats maintained on choline-adequate diets. Br J Nutr. 107:1408-12 (2012).

 

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

Ring the Bell for Magnesium Priority

*Interview with Durk Pearson and Sandy Shaw Regarding the Importance of Magnesium Priority

Epidemiological studies conducted in countries such as Germany, Sweden, South Africa, and Italy strongly suggest that low levels of magnesium in the water supply are associated with coronary heart disease.1-4  Indeed, it is now becoming clear that inadequate levels of magnesium is a ring the bell magnesiumproblem throughout the Western World, and that a lower than normal dietary intake increases the risk of hypertension, cardiac arrhythmias, ischemic heart disease, arherogenesis and sudden cardiac death.5  Moreover, shortages of serum magnesium often appear to be associated with other cardiovascular problems including coronary vasospasm.  The above data has been evident for quite some time.

 However, as Durk Pearson & Sandy Shaw point out, there are other reasons for increasing dietary supplementary intake of magnesium beyond the RDA.  If you miss the ringing of the magnesium bell and what they have to say in the following exchange, you miss at your own risk.

DURK: For many years it’s been realized that magnesium is important to cardiovascular health and inadequate quantities of magnesium lead to an increased incidence of cardiovascular disease.  Unfortunately, many of the most common sources of magnesium, such as milk of magnesia have a low bioavailability (not being fully absorbed in the body).  A few years ago the FDA proposed reducing the magnesium RDA from 400 to 200 mg.  There was such an outcry about it that they backed off. Four hundred (400) milligrams is about the lowest amount an adult ought to consider taking, and most people aren’t getting even half of that in their diet.  Most forms of magnesium are not well absorbed.  To the best of my knowledge magnesium aspartate is the best.

GREG: How much magnesium are you and Sandy taking a day?

 DURK: I was taking 4 capsules per day of  Magnesium Priority™ for a total of 400 mg per magnesiumday.  However, I’ve recently doubled that to 800 mg (8 capsules) and so has Sandy because of an interesting paper we read about loud noises (from shooting firearms) caused damage to the cochlea hair cells in the ear and even to the auditory nerve.  The scientists found that this excitotoxic damage can be partially prevented and recovery from temporary hearing loss (due to the loud noise) hastened with 700 mg a day of magnesium in the form of magnesium aspartate.

 SANDY:  This is not an adequate substitute for ear protectors when one is shooting a gun or operating noisy machinery, however.

_________________________________

For many years it’s been realized that

magnesium is important to cardiovascular

health and that inadequate quantities

of magnesium lead to an increased

incidence of cardiovascular disease.

__________________________________

GREG: Or while subjecting oneself to loud music or attending concerts, I’ll bet.

DURK: Perhaps. But the study shows that at least some excitotoxic damage can be prevented.

GREG: Is this the way that taurine operates?

DURK: Both taurine and magnesium help prevent excitotoxic damage, among other things.  And the taurine is certainly concentrated in the nervous system.  However, magnesium and taurine don’t necessarily work in exactly the same place in the excitotoxin cascade.

GREG: Can the benefit of one add to the benefit of the other?

DURK: Possibly…plausibly.

__________________________________

The scientists found that this excitotoxic

damage can be partially prevented and

recovery from temporary hearing loss

(due to the loud noise) hastened with

700 mg a day of magnesium in the

form of magnesium aspartate.

____________________________________

 GREG: Can they at least be supplementary?

DURK: They might be, but we don’t know of any data from taurine plus magnesium.  In any case we’ve increased our magnesium dose.  In addition, this probably gives us more cardiovascular protection.  There have been a lot of suggestions that 800 mg of magnesium is a good idea for cardiovascular protection; but the way we figure it, some excitotoxin damage is going on all the time.  Taking magnesium “sounds” like a good way of reducing possible damage due to inadvertent exposure.  Even though we’re not exposed to loud noises without ear protection, there’s going to be natural excitotoxin damage occurring as part of the wear and tear of everyday life and aging.

Many common sources of magnesium such as dolomite-which contains a mixture of Magnesium imagesCA22T0OKcalcium and magnesium carbonate-and milk of magnesia (magnesium hydroxide), as we’ve said, have relatively low bioavailability.

GREG: Magnesium Priority™ contains 400 mg of magnesium aspartate, as well as 80 mg of ascorbyl palmitate in 4 capsules.  If a person chooses to take 800 mg, how fast should one increase from 4 to 8 capsules per day?

DURK: Start out the first few days with just 1 capsule and then 2 and 3 and then 4; slowly build it up to 8.  If you start out right away taking 8 caps per day, you’re pretty sure to get diarrhea.

GREG: I hear you and, therefore, I intend to make Magnesium Priority™ a daily part of my dietary supplement regimen.

References:

  • Teitge JE. Incidence in myocardial infarct and mineral content of the drinking water.  Z Gesemine Inn Med. 1990; 45:478-485
  •  Marier JR, Neri LC. Quantifying the role of magnesium in the interrelationship  between human mortality/morbidity and water hardness.  Magnesium 1985; 4:53-59
  • Rubenowitz E, Axelsson G, Rylander R. Magnesium in drinking water and death from acute myocardial infarction.  Am J Epidemiol 1996; 143:456-462
  • Bernardi D, dini FL, Azzarelli A, Giaconi A, Volterrani C, Lunardi M. Sudden cardiac death rate in an area characterized by high incidence of coronary artery disease and low hardness of drinking water.  Angiology 1995; 46:145-149
  • Altura BM, Altura BT.  Cardiovascular risk factors and magnesium: relationships to atherosclerosis, ischemic heart disease and hypertension.  Magnes Trace Elem  1991; 10: 182-192
  * Life Priority Inc. products are not intended to diagnose, treat or cure any medical condition. *These Statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure or prevent any disease. The information provided is for educational purposes only. Information provided is not intended to replace the advice of your doctor or competent health care professional. Rev 2/09
Life Priority Inc. 11184 Antioch Rd. #417 Overland Park, KS. 66210   www.lifepriority.com  
800-787-5438 or 913-438-5433 Fax 913-438-5444

 

 Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

 

Why the Niacin Flush May Be Surprisingly Beneficial to Your Health – Sandy Shaw

Why the Niacin Flush May
Be Surprisingly
Beneficial to Your Health 

Why We Think It May Reduce the Risk of ALZHEIMER’S
DISEASE and Other Inflammatory Diseases,
Including Atherosclerosis, Type 2 Diabetes,
Ulcerative Colitis, Even Male Pattern Baldness

Sandy Shaw

WITHOUT PRIOR REVIEW BY DURK

It has not been read or reviewed by Durk Pearson, due to considerations that include, importantly, that time has run out and Shaw insisted on getting the paper into print without waiting. Shaw and Pearson have extensively discussed the elements of the paper so that the word “we” can be understood as the result of these discussions, but not based upon a reading of the Shaw paper by Pearson. Other than this disclaimer, everything remains as it is in the paper, with an expectation that more will be written on this subject to appear in future Durk & Sandy newsletters.

Here we explain why we think that the niacin flush (see description of flush just below this paragraph) may be a key part of the cardioprotective effect of high dose immediate-release (flushing) niacin’s highly protective effects on lipid metabolism, such as potent reductions of LDL and VLDL and triglycerides, while increasing HDL and, moreover, why the niacin flush may play an important role in reducing the risk of Alzheimer’s disease, atherosclerosis, type 2 diabetes, and other inflammatory diseases.

NOTE TO OUR READERS: This paper has become both much longer and included much more complex data and mechanistic detail to evaluate than the author (Sandy Shaw) originally anticipated. As a result, we have included in this first section of the paper the basic elements of how we believe the protective mechanism works and data on some diseases that we believe supports that interpretation. The next issue of our newsletter and subsequent issues will include the remaining parts of our analysis, with data from other diseases that we believe also appear to have significant risk reduction by the same mechanism, including detailed analysis of atherosclerosis, type 2 diabetes, and other diseases that show up in our literature searches. Sandy conceived the idea of examining the literature on the subject, read the papers discussed, and analyzed the data presented in the papers. Durk has read the analysis in detail and is in agreement with it.

WHAT IS THE FLUSH? Though we have heard it described as a transient skin reddening (from increased blood flow) accompanied by a sensation of heat associated with itching, we have come to realize that not everybody is feeling the same thing when they say “niacin flush.” The reason is that while both of us find the niacin flush AS WE EXPERIENCE IT to be pleasant, many people find it intolerable. Thus we think that what people who hate the flush mean when they say “niacin flush” is not a pleasant hot with mild itch but a hot with very unpleasant biting and burning sensations (as if being bitten by an insect or stabbed with tiny knives). In studying the mechanisms involved in the niacin flush to the extent they are now understood, we have an idea why many people are having this unpleasant flush. After we have discussed how we understand some of what causes the niacin flush, we will explain what we think may be making it intolerable for many. See below in section on “What Is Intolerable About the Niacin Flush?”

We understand, then, that some people can’t tolerate the niacin flush (caused by acute release of the prostaglandin PGD2) and, as a result, won’t use high dose plain niacin. It may be possible to reduce the flush to a tolerable level and, if so, it might be a much more sensible strategy (so you would end up with a flush like what we experience) than eliminating the flush if you want to get niacin’s lipid-lowering benefits. What has happened to niacin research, however, as a result of this crash program by certain drug companies to get rid of the flush, is that data on plain niacin and the effects of the acute release of prostaglandin D2 (which induces the flush) have to a considerable extent disappeared as more and more research focuses on the “extended release” or other non-flushing versions of niacin, which are not the same as plain niacin. “Extended release” niacin is not the same as plain niacin, for which extensive literature exists showing its potent lipid benefits. You do not see very much in the literature on head to head comparisons of “non-flushing niacin” (ersatz niacin) to plain (flushing) niacin in humans to identify what it is that the flush is doing.

THE KEY TO UNDERSTANDING THE EFFECTS OF THE PGD2-CAUSED NIACIN FLUSH IS TO REALIZE THAT IN ITS ACUTE RELEASE, PGD2 ACTS IN MANY MODEL SYSTEMS AS AN ANTI-INFLAMMATORY. IN ITS CHRONIC RELEASE, PGD2 APPEARS TO BE USUALLY PRO-INFLAMMATORY, but depending on the rate at which PGD2 is released, the amount released, and the state of inflammation in the tissue where it is released, you can get a pro-inflammatory or an anti-inflammatory effect. As the old saying goes, the devil is in the details and it is the rush to avoid considering the details so as to rapidly develop a non-flushing niacin that is leading to the rash abandonment by some drug companies and health practitioners of flushing (immediate-release or plain) niacin.

It has long been known that the prostaglandins PGD2 and PGE2 are responsible for inflammation induction (Haworth, 2007). Later in the biosynthetic pathways of these prostaglandins, anti-inflammatory circuits are induced (Haworth, 2007). Here is where we believe is the source of a major misunderstanding concerning the pro-inflammatory or anti-inflammatory effects of PGD2, the prostaglandin that causes the niacin flush: A CHRONICALLY HIGH LEVEL OF A SIGNALING MOLECULE, SUCH AS PGD2 (generally pro-inflammatory when at a chronically high level) CAN INTERFERE WITH SIGNALS BY ACUTELY RELEASED (PULSATILE) AMOUNTS OF THAT SIGNALING MOLECULE (generally anti-inflammatory) BY THE ACUTE SIGNAL SIMPLY BEING “LOST” IN THE NOISE OF THE CHRONICALLY HIGH LEVEL OF THAT MOLECULE. Hence, we think that chronically high levels of PGD2 are likely to prevent or reduce the effect of acute signals of PGD2 that would otherwise be anti-inflammatory. See sections on Alzheimer’s disease (AD) below, where chronically high PGD2 signaling is thought to be a major cause of the neurodegenerative features characteristic of AD (Maesaka, 2013).

  • Haworth and Buckley. Resolving the problem of persistence in the switch from acute to chronic inflammation. Proc Natl Acad Sci U S A. 104(52):20647-8 (2007).
  • Maesaka, Sodam, Palaia, et al. Prostaglandin D2 synthase: apoptotic factor in Alzheimer plasma, inducer of reactive oxygen species, inflammatory cytokines, and dialysis dementia. J Nephropathol. 2(3):166-80 (2013).

In this section, we look at PGD2 release in model systems:

DATA ON ACUTE AND CHRONIC RELEASE OF PGD2

Prostaglandin D2 in the Resolution of Inflammation
Ulcerative Colitis

There is considerable difficulty in interpreting the huge amount of scientific literature on prostaglandins when you read that a certain tissue level is associated with a certain stage of an inflammatory disease. Most of the literature that we’ve seen is bogged down with difficulties in interpreting the role of the prostaglandin in the inflammatory process because of not knowing whether the tissue level measured is part of a pulsatile release or a chronic release.

A very interesting recent paper (Vong, 2010) was published by scientists who believe that the increased expression of prostaglandin D2 synthesis and its EP1 receptor that they detected in individuals in long-term remission from ulcerative colitis suggest that the release of PGD2 in response to acute releases of inflammatory stimuli could be important antiinflammatory protection to maintain colonic mucosal homeostasis.

To study this phenomenon in human patients, the scientists took rectal biopsies from patients with active ulcerative colitis, which have elevated levels of PGE2, PGI2, and PGF2alpha. “Several studies of experimental colitis suggest important roles for PGD2 in promoting the resolution of inflammation and long-term alterations in colonocyte and barrier function …” They examined PGD2 levels in biopsies for ulcerative colitis patients, comparing them with those of healthy individuals who had no prior history of UC or those from healthy individuals who had experienced a prior bout of UC but had been in remission without medication for >4 years. “We observed a pronounced elevation of PGD2 synthesis and DPI receptor expression only in healthy individuals with a prior history of UC. In these individuals, as has been observed in animal studies, the elevated mucosal PGD2 may contribute to the maintenance of colonic tissue homeostasis and possibly, also to an increased risk of colorectal cancer.”

One difficulty here is that the biopsy represents a snapshot of PGD2 levels at one point. Was the PGD2 being released as an acute pulse at that point or was it being measured at a chronic level? The authors are hot to track down the cause of this association (the apparent anti-inflammatory effect of PGD2 in maintaining remission in UC) and say, “we believe that PGD2 plays an important role in the initial maintenance of mucosal homeostasis.” We might as well add our own hypothesis to the mix. On the basis of other data on anti-inflammatory effects of pulsatile release of PGD2, we would expect the most protective effects of PGD2 release in this model to occur at an optimal level of a pulse of PGD2 released over a limited time period in response to pro-inflammatory stimuli, but not too little to prevent inflammation so as to maintain remission, or too much to increase PGD2 to levels that would potentiate inflammation and, perhaps, be part of an increased risk of colorectal cancer the scientists here mention as a possibility.

For example, the scientists note that their results are “consistent with studies of rodents in which prolonged elevations of PGD2 synthesis were observed after resolution of colitis.” This prolonged elevation contributed not only to resolution of inflammation but also to “long term alterations in epithelial function, some of which may have contributed to an increased susceptibility to colon cancer.” This suggests that the protective response of the immune system in some animals and humans of increasing PGD2 release in response to inflammation to modulate that inflammation may go too far and result in long-term adverse effects such as increased risk of colon cancer. It appears to us that pulsatile PGD2 release a few times a day with immediate release niacin supplementation may offer better protection against a variety of inflammatory diseases.

  • Vong, Ferraz, Panaccione, et al. A pro-resolution mediator, prostaglandin D(2), is specifically up-regulated in individuals in long-term remission from ulcerative colitis. Proc Natl Acad Sci U S A.107(26):12023-7 (2010).

MALE PATTERN BALDNESS (Nieves, 2014)

The hair follicle in male pattern baldness balding areas (but not in normal hair of balding men) have chronically high levels of prostaglandin D2 accompanied by lower levels of prostaglandin E2. One way that minoxidil has been found to work is by increasing prostaglandin E2, which in this model “normalizes” the PGD2/PGE2 ratio. However, PGE2 is an inflammatory molecule, so you wouldn’t want to increase it very much, and that is undoubtedly the “secret” of minoxidil, to NORMALIZE the ratio of PGD2/PGE2 so as to eliminate a chronically high PGD2 level.

One of the signals of the catagen phase of hair growth, where hair growth ceases for a time and some hair follicles die, is the release of very large amounts (7 fold higher than baseline) of PGD2 (Nieves, 2014). For that reason, there is interest in blocking PGD2 as a “treatment” for balding. But once again, there is a risk that blocking PGD2’s unwanted effects will also block important beneficial effects of PGD2. This, not surprisingly, is a major problem in medicine, that the change you want in a certain tissue at a certain time and by a certain amount may cause harm elsewhere where you do not want that change.

  • Nieves and Garza. Does prostaglandin D2 hold the cure to male pattern baldness? Exp Dermatol. 23(4):224-7 (2014).

ANTI-INFLAMMATORY ROLE OF PGD2 IN ACUTE
LUNG INFLAMMATION (Murata, 2012)

The authors of this paper (Murata, 2012) studied the role of PGD2 signaling in acute lung injury (ALI). Administering endotoxin (lipopolysaccharide (LPS), a potent bacterial inflammatory factor) increased edema and neutrophil infiltration into the wild type mouse lung, typical effects seen in inflammation. “Treatment with either an agonist to the PGD2 receptor, DP, or a degradation product of PGD2, 15-deoxy-delta12,14-PGJ2, exerted a therapeutic action against ALI.” The effect of LPS inhalation by the wild type mice peaked on day 1, hence this was an acute effect. The authors found, however, that whether PGD2 had an anti-inflammatory effect or a pro-inflammatory effect depended upon the stage at which the PGD2 was administered, with PGD2 at later stages of ALI being anti-inflammatory (reducing the invasiveness of neutrophils).

  • Murata, Aritake, Tsubosaka, et al. Anti-inflammatory role of PGD2 in acute lung inflammation and therapeutic application of its signal enhancement. Proc Natl Acad Sci. 110(13):5205-10 (2013).

ALZHEIMER’S DISEASE: MICROGLIAL PGE2
(PROSTAGLANDIN E2) SIGNALING VIA EP4
RECEPTOR SUPPRESSES ALZHEIMER
ASSOCIATED INFLAMMATION

A signaling system is reported here (Woodling, 2014) that the authors found to regulate an important protective anti-inflammatory mechanism in the early stages of Alzheimer pathology that decreases significantly (along with its protective effect) as the disease progresses. This is a signal from the prostaglandin PGE2 to its EP4 receptor. See section below on the PGE2 receptor system (EP1, 2, 3, and 4) and new findings suggesting that it is a key to some of the antiinflammatory properties of DHA (docosahexaenoic acid, an omega 3 fatty acid found in fish oils) and possibly that of curcumin.

As reported in a 2012 paper (Ruan, 2012), the EP1 receptor for PGE2 appears to be the key target for DHA and fish oils. There they showed that, in cultured stromal cells, the IC50 for fish oil (that is, the amount that inhibited 50% of the PGE2 activity) was 18 mg/L or 54 μM. The authors calculated that, for a 150 pound human containing 4-5 liters of blood, “consuming 100 mg. fish oil should yield IC50 results.” (This depends, of course, on how the DHA partitions in the blood and tissues, but the calculation provides a crude estimate.) The authors then indicate that they would recommend taking 500-1000 mg fish oil daily on the basis of their findings.

It is interesting to note the opposing effects of PGD2 (the prostaglandin that induces the niacin flush) and PGE2 in the balding model (above), where chronically high PGD2 resulted in suppression of PGE2. A pulsatile release of PGD2 (an ACUTE release) as in the niacin flush would be anti-inflammatory, not pro-inflammatory as with chronically high PGD2. Hence, you could see an INCREASE in PGE2 by suppressing chronically high PGD2. The balding model, in fact, shows hair growth and the cessation of hair follicle death resulting from slight modulation in the ratio of PGD2/PGE2, in which PGE2 is increased, while chronically high PGD2 levels are reduced to “normalize” the ratio. The niacin flush causes pulsatile, not chronic, release of PGD2. It is relevant to note that another paper (see just below) describes CHRONICALLY high PGD2 signalling in full-blown Alzheimer’s. We predict, in fact, that high dose niacin in the immediate-release flushable form will REDUCE the risk of Alzheimer’s, and that getting rid of the flush would probably eliminate this protective effect. If you could get rid of the flush and still retain all the protective benefits of the flush, then fine, go ahead and get rid of it. But so far, the focus seems to be on suppressing the flush without adequately understanding what the flush has to do with the protective effects of immediate release niacin.

Also, note in the urate crystal inflammation model (below) that a 5.2 fold pulsatile (acute) increase in PGD2 was anti-inflammatory, decreasing inflammatory signaling by PGE2. The opposing effects of certain dose and time-dependent releases of PGD2 and PGE2 would appear to be a system to examine closely in relation to Alzheimer’s.

  • Woodling, Wang, Priyam, et al. Suppression of Alzheimer-associated inflammation by microglial prostaglandin-E2 EP4 receptor signaling. J Neurosci.34(17):5882-94 (2014).
  • Ruan and So. Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E. BMC Complement Altern Med.12:143 (2012).

ALZHEIMER’S DISEASE:
INCREASED LEVELS OF A FORM OF
PGD2 SYNTHASE

In a very complex analysis (Maesaka, 2013), researchers found that a form of PGD2 synthase, L-PGDS, can in a chain of biochemical reactions, convert arachidonic acid to 15deoxyPGdelta12,14 J2(15dPGJ2), the primary ligand for peroxisome proliferator activator receptor gamma (PPARgamma), and that 15dPGJ2 has been reported to induce apoptosis in human astrocytes and cortical neurons, which could be prevented by inhibitors of L-PGDS, such as IGF, insulin, and erythropoeiten as well as PGE1, PGE2, and COX2 and caspase inhibitors. The authors identified L-PGDS “as a dominant inducer of apoptosis in AD plasma,” presumably by increasing PGD2 signalling to a chronically high level.

  • Maesaka, Sodam, Palaia, et al. Prostaglandin D2 synthase: apoptotic factor in Alzheimer plasma, inducer of reactive oxygen species, inflammatory cytokines, and dialysis dementia. J Nephropathol. 2(3):166-180 (2013).

Interestingly, another paper (Ryan, 2008) reports that 15dPGJ2 (that as noted just above induces apoptosis in brain astrocytes and cortical neurons) impairs phosphatidylcholine synthesis by promoting cysteine cross-linking in the enzyme cytidyltransferase alpha. This cross-linking could be reduced by N-acetylcysteine (Ryan, 2008).

The sleep impairments observed in Alzheimer patients may be, at least to some extent, linked to chronically high PGD2 signaling, as PGD2 is an important sleep-inducing molecule (Urade 1999). The signal of a transient pulse of a substance is lost in the noise of a continuously high background level of that substance.

  • Ryan, Chen, Vennalaganti, et al. 15-deoxy-delta12,14-prostaglandin J2 impairs phosphatidylcholine synthesis and induces nuclear accumulation of thiol-modified cytidyltransferase. J Biol Chem.283(36):24628-40 (2008).
  • Urade and Hayaishi. Prostaglandin D2 and sleep regulation. Biochim Biophys Acta. 1436:606-15 (1999).

REDUCTION OF URATE CRYSTAL INFLAMMATION
BY ACUTELY ELEVATED PGD2

After struggling through the analysis of prostaglandin D2 synthase’s link to apoptosis in Alzheimer’s disease (just above this paragraph), if you did, you may be hoping for something a little simpler. This one is.

Here, researchers found (Jung, 2007) that in mice fed root extracts of traditional oriental medicinal plants,* inflammation elicited by injecting 2 mg of monosodium urate crystals into the pouch resulted in a rapid and dramatic decrease in the measured inflammatory parameters, including neutrophil density, IL-6 and TNFalpha mRNA. Leukocyte count, IL-6, prostaglandin E2, along with prostaglandin D2 were examined in the pouch exudate. Remarkably, the concentration of the potentially anti-inflammatory Prostaglandin D2 rose 5.2 fold. The authors of this 2007 paper were very excited about these results and thought this could point to a novel way to treat inflammation, the cause of the intense pain of uric acid crystals in gout. They seem to have been right, but nothing appears to have come of this.

* Dried roots of Acanthopanax senticosus, Angelica sinensis, and Scuttelaria baicalensis.

  • Jung, Schumacher, Kim, et al. Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels. Arthritis Res Ther.9:R64 (2007).

PGD2 IN THE SKIN

A recent paper (Shimura, 2010) reports on the role of PDG2 in allergic responses in the skin, focusing on mast cells expressing the hematopoeitic PGD synthase found in dendritic cells. They discussed rapid excretion of PDG2 in response to various allergens, including an irritant compound. “A possible anti-pruritic [anti-itch] potential of PGD2 in the scratching behavior of mice was recently proposed.” [It was AFTER Sandy performed the experiment on her itchy skin described just below that she read about this finding. Serendipity!] When released rapidly in response to allergens, PGD2 can act as an anti-inflammatory, while when released in excess quantities it exacerbates the allergic response (Shimura, 2010).

  • Shimura, Satoh, Igawa, et al. Dendritic cells express hematopoietic prostaglandin D synthase and function as a source of prostaglandin D2 in the skin. Am J Pathol.176:227-37 (2010).

SANDY’S ITCHY SKIN—DISCOVERING THE EFFECT OF
ELIMINATING THE NIACIN FLUSH THE HARD WAY

Sandy had developed an itchy skin condition (probably a result of severe hypothyroidism) and had, as a result, discontinued high dose niacin about a month ago because of increased itchiness and of stabbing sensations (see description of the niacin flush above) during the flush. The itchiness got worse until it became such a serious problem that she had to take two prescription drugs to keep the itchiness under control. Hydrocortisone cream didn’t help at all, which is consistent with the reported effect of chronically elevated PGD2 in blunting the antiinflammatory effect of corticosteroids (Barnes, 2009). This doesn’t PROVE that it was chronically high PGD2 in her skin that made the hydrocortisone salve ineffective, but is consistent with data showing that effect. As a matter of fact, Sandy has a mild case of COPD, which is reported to exhibit resistance to the antiinflammatory effects of corticosteroids, suggesting the possibility that she has chronically elevated PGD2 in her lungs. The fact that it hasn’t gotten progressively worse over the years, as COPD typically does, MAY be due to her ingestion of high dose immediate-release niacin which could be reducing the inflammatory activity by discharging the release of PGD2 via pulses, thereby preventing chronic PGD2 release as a sort of constant dribble rather than as pulses. This is our hypothesis. There might be another way to explain all this, and we certainly can’t prove there isn’t (given that it is impossible to disprove a negative), but we think our explanation is quite plausible and consistent with all the data we’ve seen.

It is interesting to note that curcumin restores corticosteroid sensitivity in monocytes exposed to oxidants by maintaining HDAC-2 (histone deacetylase 2) levels (Gonzalez, 2012); HDAC-2 levels are known to be reduced in COPD. Could this be another example of a natural substance that reduces chronically high levels of PGD2? It is certainly consistent with a large amount of the literature on COPD, PGD2, and HDAC-2.

  • Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol.71:451-64 (2009).
  • Gonzalez, Ballester, Lopez-Posadas, et al. Effects of flavonoids and other polyphenols on inflammation. Crit Rev Food Sci Nutr. 51(4):331-62 (2011).

EXPERIMENT: When I (Sandy) realized that it might be the loss of the flush that was causing my monster skin itch, I took 400 mg of niacin on an empty stomach to induce the flush. After that, the flush ensued and went on for the normal period of time it usually does after I take niacin, during which the itching was intensified, the itching then subsiding to a very low level. Plus, a little bonus, my painful knee osteoarthritis had become much less painful when I went out to the supermarket a few minutes later. It had become worse during the month I was off high-dose niacin. NOTE: I still took Personal Radical Shield during this period and so was getting between 250 and 500 mg/day of niacin, but my regular dose of niacin was around 2 grams a day in addition to that.

For a relationship between osteoarthritis and prostaglandin D2, see:

  • Zayed, Li, Chabane, et al. Increased expression of lipocalin-type prostaglandin D2 synthase in osteoarthritic cartilage. Arthritis Res Ther. 2008, 10(6):R146 doi:10.1186/ar2581 (2008).

Mitigation of Inflammation with Foods

A 2012 paper (Wu, 2012) reported that polyphenols and other compounds found in foods such as fruits, berries, vegetables, nuts, whole grains, and foods of marine origin contain components can “play an important role in attenuating and mitigating chronic pro-inflammatory processes associated with chronic diseases,” such as atherosclerosis, ischemic heart disease, cancer, obesity, inflammatory bowel disease, Crohn’s disease, diabetes and autoimmnune diseases. Surprisingly few papers on the mitigation of inflammation discuss prostaglandins explicitly, revealing that there is an immense area here where increased knowledge could promote improvements in controlling the chronic inflammatory diseases associated with aging.

When you control a biochemical pathway to regulate processes taking place far downstream, it is usually best to think of ways to regulate closer to the downstream site that is a problem because regulation at the upper end of the chemical pathway will affect many processes that have nothing to do with your problem and may produce unwanted off-target effects. THAT, in fact, is one of the major problems with statins … that their effects are taking place far upstream in the process of synthesizing cholesterol (Cederberg, 2015) and there are frequent undesired effects such as myopathy and an alarmingly high increased risk of developing type 2 diabetes.

  • Wu and Schauss. Mitigation of inflammation with foods.J Agric Food Chem.60:6703-17 (2012). Cederberg, Stancakova, Yaluri, et al. Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort. 58:1109-17 (2015).

STATINS IN COMBINATION WITH NIACIN

As we note in the paragraph above, statins have been found to reduce insulin sensitivity, and this is associated with a large increase in the risk of developing type 2 diabetes. The combination of statins with niacin also have a significant effect in reducing the beneficial effects of increased HDL cholesterol that is seen with immediate release niacin (Keene, 2014). The mechanism that causes statins to increase the risk of type 2 diabetes are, we think, a likely place to look for what causes this adverse effect of statins on the protective effect of niacin on reduced risk of non-fatal heart attacks, the most common kind of heart attack.

Most Heart Attacks Are Non-Fatal, So the Reported
Highly Protective Effect of Niacin Against the
Incidence of Non-Fatal Heart Attacks Is Important

In a paper (Keene, 2014) providing a meta-analysis of 117,411 patients, very interesting differences between the effects of niacin taken by patients NOT RECEIVING STATINS (BEFORE THE STATIN ERA) and those who, later, were taking niacin and statins emerged. Very statistically significant results showed that in those patients NOT taking statins, niacin was associated with a significant reduction in non-fatal heart attacks (myocardial infarction) (odds ratio was 0.69, 0.56 to 0.85, p=0.0004). However, in studies where statins were already being taken, niacin showed no significant effect on the incidence of non-fatal heart attacks. The researchers say, “In the current era of widespread use of statins in dyslipidaemia, substantial trials of these three agents [niacin, fibrates, or CETP inhibitors, all of which increase HDL levels] do not support this concept [that increasing HDL would generally reduce cardiovascular events].” Statins interfere with an important protective effect of niacin. It is important to note that NON-FATAL MYOCARDIAL INFARCTIONS are the most COMMON type of heart attack, so reduction of these heart attacks is not at all unimportant, though the word FATAL may be somewhat distracting from the significance of these results.

Studies with statins HAVE repeatedly shown that reductions in LDL cholesterol with statins “has repeatedly been found to reduce cardiac events and all cause mortality in the setting of both secondary and primary prevention.” However, the increased protection against cardiovascular events expected by increased HDL has not been seen. See paragraph above. Hence, something in the interaction of statins with niacin and fibrates, where niacin and fibrates increase HDL cholesterol and which (when taken WITHOUT CONCURRENT INGESTION OF STATINS), reduces the risk of non-fatal myocardial infarctions, results in a loss of that protective effect of niacin or fibrates.

The studies with niacin were confounded by the fact that some of the patients were given aspirin or laropriprant to inhibit flushing. Laroopriprant is thought to interfere with prostaglandin pathways which, as you will see below in our discussion of prostaglandins, could be very important, and the authors of this paper (Keene, 2014) suggest that this effect “could confound the effect of niacin.”

  • Keene, Price, Shun-Shin, and Francis. Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients. 349:g4379 (2014) doi: 10.1136/bmj.g4379 (18 July 2014).

2012 REVIEW PAPER ON PGD SYNTHASE AND PGD2
IN IMMUNE RESPONSE (Joo, 2012)

A good recent review of PGD synthase and PGD2 described a variety of model systems in which PGD2 exhibited a proinflammatory or antiinflammatory effect. For example, a paper is cited in which a human model of an acute inflammatory response induced by the administration of LPS provides data “strongly” supporting anti-inflammatory effects of PGD2. PGD2 and its cyclopentenone prostaglandin derivatives are reported by the review’s authors to have antiinflammatory properties with functions in the resolution of inflammation, and “there is considerable interest in the importance of PGD2 and its distal products in the mediation and resolution of inflammation.” (Joo, 2012). Other models show pro-inflammatory effects. The devil is in the details of the amounts released, the time course over which the release takes place, and the inflammatory milieu of the tissue involved (as we have noted above, an acute signal of a molecule released into an environment with a high chronic level of that molecule may not convey the acute signal very well or at all).

  • Joo and Sadikot. PGD synthase and PGD2 in immune response. Mediators Inflamm. 2012:503128. doi: 10.1155/2012/503128 (2012).

Interestingly, in sleeping sickness, PGD2 is increased and the microorganism responsible for the disease has been shown to induce the production of PGD2 in culture. PGD2 is a well-known sleep promoting prostaglandin. The review authors (Joo, 2012) published a paper earlier in which they showed that PGD2 inhibits a “key proinflammatory immunoglobulin cell surface receptor TREM-1 in vitro in macrophages.” In another of the authors’ papers, they showed that the administration of PGD2 in a mouse model of P. aeruginosa lung infection resulted in enhanced clearance of P. aeruginosa from the lungs. Moreover, their study showed that mice that had COX-2 inhibited (via knockout) had enhanced clearance of the bacterium and that this effect was related to a decrease in PGE2. There we see the interaction and apparent opposing effects between PGD2 and PGE2 that has appeared in other studies.

This paper is useful for presenting an analysis of several models of inflammation and the effects of various forms of PGD2-synthase and PGD2.

PGE2 RECEPTOR SYSTEM

The inducible and inflammatory COX-2 pathway synthesizes the release of inflammatory amounts of PGE2 (Ruan, 2012). There are three different PGE2 synthases, enzymes that manufacture PGE2 from arachidonic acid. The PGE2 produced is then received by one of four PGE2 receptors, EP1, 2, 3, and 4), which is associated with pain, vascular diseases, and cancer cell growth (Ruan, 2012). DHA’s anti-inflammatory effects are mediated, at least in part, by its action at the EP1 receptor of PGE2 (Ruan, 2012) while the antiinflammatory action of curcumin is reported to be via the reduction of IL-1 beta-stimulated microsomal PGES. PGES enzymes convert the prostaglandin PGH2 to PGE2 (Kats, 2013).

  • Ruan and So. Screening and identification of dietary oils and unsaturated fatty acids in inhibiting inflammatory prostaglandin E. BMC Complement Altern Med.12:143 (2012).
  • Kats, Bage, Georgsson, et al. Inhibition of microsomal prostaglandin E synthase-1 by aminothiazoles decreases prostaglandin E2 synthesis in vitro and ameliorates experimental periodontitis in vivo. FASEB J.27:2328-41 (2013).

YIN-YANG BALANCE BETWEEN
PROINFLAMMATORY AND ANTI-INFLAMMATORY
PROSTAGLANDINS

This is what some researchers refer to as a “yin yang” system, where you have (for example) prostaglandins PGE2 and PGD2 working a balance of pro-inflammatory and anti-inflammatory effects depending on how much is released, the time course of the release, and the inflammatory milieu of the tissue where they are released. Acute inflammation onset and resolution have also been identified in a paper (Rajakariar, 2007) as being regulated by the balance of PGD2 and 15d-PGJ2.

  • Rajakariar, Hilliar, Lawrence, et al. Hematopoietic prostaglandin D2 synthase controls the onset and resolution of acute inflammation through PGD2 and 15-deoxy-delta12,14 PGJ2. Proc Natl Acad Sci U S A. 104(52):20979-84 (2007).

“The devil may be in the details,
But so are the angels.”

—Sandy Shaw

It would appear that all of the most important chronic diseases of man, including cardiovascular disease, cancer, and Alzheimer’s disease are critically regulated by this sort of balancing act. The devil may be in the details, but so are the angels. Another way of putting it is that you shouldn’t be in too great a rush to throw out the devils until you understand whether, by doing so, you are throwing out some or all of the angels.

What Is Intolerable About the Niacin Flush?

The niacin flush appears to be the devil in the details that most disturbs people who would use niacin but can’t stand the flush. There are many interacting biochemical pathways regulating pro-inflammatory and anti-inflammatory effects in the skin, but it would be helpful to isolate some particularly important players in the niacin flush. First, of course, is PGD2, the acute release of which is closely associated with the strength and timing of the flush in relation to when you took the niacin. Preventing the acute release of PGD2 comes close to getting rid of the flush, but doesn’t eliminate it entirely, pointing to other regulatory factors being involved (Kamanna, 2009).

But there are a number of different prostaglandins that have interactions with each other and can counter-regulate each other, and so on. Importantly, as we describe above, PGE2 seems to be in a balancing act with PGD2 in some models of inflammation, so that the nastiness of the niacin flush MAY be linked to the release of PGE2 (our supposition). A prediction of this hypothesis would be that inhibitors of the release of PGE2 would reduce how much of the nasty burning and sensations of insects biting would occur during the flush. A recent paper (Gonzalez, 2012) reported that a study of the inhibitory effects of flavonoids on the release of PGE2 in peritoneal macrophages found that some flavonoids were as effective as aspirin in this inhibitory activity, including quercetin, resveratrol, apigenin, genistein, or kaempferol, but the authors were surprised that luteolin, fisetin, or morin did NOT inhibit the PGE2 release in the peritoneal macrophages.

Here, again, we have another remarkable little clue on the psychodynamics of the niacin flush: a paper (Papaliodis, 2008) that reports that luteolin suppresses the niacin flush!! Another piece for the puzzle of what the niacin flush is all about. Moreover, to add a little additional spice to this, it has been reported (Ren, 2009) that some flavonoids produce a little skin flush of their own. The paper (Gonzalez, 2012) also mentioned that flavonols appear to exert the highest activity (in papers on anti-inflammatory effects via inhibition of lipoxygenases). Cocoa is an excellent source for flavonols. We are currently taking a flavonol-enriched supplement (expensive, however) called Cocoa-Via® as a source of these flavonols.

  • Kamanna, Ganji, Kashyap. The mechanism and mitigation of niacin-induced flushing. Int J Clin Pract.63(9):1369-77 (2009).
  • González, Ballester, López-Posadas, et al. Effects of flavonoids and other polyphenols on inflammation. Crit Rev Food Sci Nutr. 51(4):331-62 (2011).
  • Papaliodis, Boucher, Kempuraj, and Theoharides. The flavonoid luteolin inhibits niacin-induced flush. Br J Pharmacol. 153:1382-7 (2008).
  • Ren, Kaplan, Hernandez, et al. Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G). J Lipid Res. 50:908-14 (2009).

REDUCING THE NIACIN FLUSH

A recent paper (Jacobson, 2010) that discussed in amazing detail how to reduce the niacin flush begins by noting that “[n]iacin is the most effective lipid modifying agent for raising high density lipoprotein [HDL] cholesterol …” The author explains that in clinical trials, over 60% of niacin users experienced mild or moderate flushing, with 5% to 20% of patients discontinuing niacin therapy because of the flush.

The author (Jacobson, 2010) goes on to explain various ways to reduce the flush, including taking niacin with meals or at bedtime with a low-fat snack and avoiding exacerbating factors such as alcohol or hot beverages. He also indicates that taking 325 mg of aspirin along with niacin suppresses the flush. However, aspirin has many effects on prostaglandin chemistry and as prostaglandins appear to play an important role in the beneficial cardioprotective effects of niacin, we do not recommend taking aspirin along with niacin to reduce the flush.

  • A “hot” topic in dyslipidemia management—“How to Beat a Flush:” optimizing niacin tolerability to promote long-term treatment adherence and coronary disease prevention. Mayo Clinic Proc. 85(4):365-79 (2010).

IN THE BEGINNING,
THERE WAS IMMEDIATE RELEASE NIACIN

To get some feel for the data on clinical effects of immediate release niacin over its first fifty years of use, a paper published in 2005 in the Journal of Internal Medicine (Carlson, 2005) provides an informative review. At this point, the switchover to the non- flushing niacin had not occurred to a great extent, as Niaspan had just become available. Hence, the review focused largely on immediate release niacin that caused a strong flush. Indeed, the author of this review (Carlson, 2005) had been doing pioneering work on niacin for over 40 years.

It was discovered early (some of the early data were published by the author of this review with a coauthor (see Carlson, 1962) that nicotinic acid (niacin) lowers free fatty acids by inhibiting the mobilization of free fatty acids from adipose tissue, a process called lipolysis; the antilipolytic effect of niacin is now considered a major source of the benefits of niacin. The early researchers found that the inhibition of mobilization of free fatty acids by niacin did not change the overall energy metabolism in the heart but “switched its oxidative metabolism from lipids to carbohydrates.” This is a major effect of niacin in its protective cardiovascular role. The inhibitory effect of niacin on the rise of free fatty acids and triglycerides that occurs during emotional stress was reported in a 1962 paper (Carlson, 1962) on experiments in humans.

As of the date of this review, the author stated, “[i]t is now generally accepted that nicotinic acid is the most powerful drug for raising the concentration of HDL, in particular the subspecies HDL2.” He cites data from a study that found HDL cholesterol to rise by 50% in hyperlipidemic patients, but the subfraction of HDL2, the large HDL particles, increased by almost 100%.

Interestingly, the author referred to data showing that at that time researchers had already identified the niacin flush as being due to the release of prostaglandins (by experiments using the prostaglandin synthesis [cyclooxygenase] inhibitor indomethacin) and found that indomethacin markedly reduced the flush. Other studies published before the Carlson 1962 review suggested that PGD2 might be the prostaglandin responsible for the flush.

Carlson in that review also mentioned the discovery that niacin had fibrinolytic (clot busting) effects, having been shown to decrease the plasma levels of fibrinogen by 15% by inhibiting its synthesis by plasminogen activator inhibitor 1. The increased expression of PAI-1 was discussed by Carlson as being closely associated with hypertriglyceridemia (Carlson, 1962). A recent paper (Song, 2012) proposed that PGD2, which the authors found to be synthesized by COX-1 in platelets in both mice and humans, may “function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during [flushing] niacin therapy.”

  • Nicotinic acid: the broad-spectrum lipid drug: a 50th anniversary review.J Intern Med. 258:94-114 (2005).
  • Carlson and Oro. The effect of nicotinic acid on the plasma free fatty acids; emonstration of a metabolic type of sympathicolysis. Acta Med Scand. 172:641-5 (1962).
  • Song, Stubbe, Ricciotti, et al. Niacin and biosynthesis of PGD2 by platelet COX-1 in mice and humans. J Clin Invest. 122(4):1459-68 (2012).

CONCLUSION:

In conclusion, there is a rush to develop a way to evade the niacin flush that causes an acute release of PGD2 in the use of niacin therapy to treat hyperlipidemia. This incredible rush, that has resulted in nearly a discontinuation of research on immediate release niacin is being done almost entirely for the purpose of making a non-flushing niacin available for commerce because it could make somebody a lot of money. Because of the entwined interests of government regulatory authorities at the FDA (users’ fees are a very important part of the FDA’s budget) and certain pharmaceutical companies which could benefit by the availability of such a non-flushing niacin product, this work is not (in our opinion) properly scientifically evaluating what it means to eliminate the niacin flush and what it might cost patients using the new forms of niacin (taking into account that many such patients would never take the flushing niacin in the first place) by actually comparing the two different forms of niacin. No such evaluation seems to be taking place. Just thought we ought to mention it …

The correct question that should be asked is not whether extended-release niacin has equivalent benefits to regular niacin—it doesn’t —but what benefits does it provide to which patients and what are its risks, questions that should be asked of any medicine. The almost desperate pursuit of “equivalence” between the two resembles a morbid fear of admitting that somebody might be giving up something of value by taking extended release niacin rather than immediate release niacin and—horror of horrors—finding out exactly what that something of value really is.

HUMAN STUDIES WITH “EXTENDED RELEASE” OR
“PROLONGED RELEASE” NIACIN LEAVE LITTLE
ROOM FOR DOUBT ABOUT THE LACK OF
EQUIVALENCE WITH THE BENEFITS OF
IMMEDIATE RELEASE NIACIN

  1. A human study of extended-release niacin on lipoprotein particle size, distribution and inflammatory markers in patients with coronary artery disease (Kuvin, 2006) found that compared with subjects who received placebo, 3 months of ER niacin resulted in significantly increased though “relatively small” increases in HDL and no significant change in total LDL levels. Regular niacin provides a very significant and clinically meaningful reduction in LDL. The patients participating in this study already had well-controlled LDL (that is, by prior treatment not including any form of niacin), so this study really did not explore the differences between ER niacin and immediate release niacin on the regulation of lipids.
  • Kuvin, Dave, Sliney, et al. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease. Am J Cardiol. 98:743-5 (2006).
  1. In another human study (Plaisance, 2008), the effects of aerobic exercise and ER niacin were examined in 15 men with the metabolic syndrome. ER niacin lowered fasting but had no effect on the postprandial triglyceride AUC (amount under the curve), while it did decrease the insulin AUC. Immediate release niacin, however, reduces fasting triglycerides by 20-50%.
  • Plaisance, Mestek, Mahurin, et al. Postprandial triglyceride responses to aerobic exercise and extended-release niacin. Am J Clin Nutr. 88:30-7 (2008).
  1. In a third human trial (Jafri, 2009), ER niacin reduced LDL particle number and increased the number of HDL particles without changing total LDL cholesterol in patients with stable coronary artery disease. But the very significant lowering of LDL is considered a major protective feature of immediate release niacin.
  • Jafri, Alsheikh-Ali, Mooney, et al. Extended-release niacin reduces LDL particle number without changing total LDL cholesterol in patients with stable CAD [coronary artery disease]. J Clin Lipidol. 3:45-50 (2009).
  1. In another human trial (Westphal, 2006) (randomized, placebo-controlled double blind, 30 men with metabolic syndrome), a short term (6 week) treatment with ER niacin increased adiponectin by 56% and leptin by 26.8% but there was no change in the levels of the proinflammatory factors TNFalpha, IL-6 and C-reactive protein, no improvement in endothelial function (as measured by FMD), and an actual deterioration in glucose and insulin parameters. Despite increased levels of adiponectin, the authors note that this “fails to improve atheroprotective functions attributed to adiponectin, such as insulin sensitivity, anti-inflammation, and endothelial function.”
  • Westphal, Borucki, Taneva, et al. Extended-release niacin raises adiponectin and leptin. 193:361-5 (2007).

A review paper (Vosper, 2009) looking at niacin’s effects on prostaglandin chemistry, came to the conclusion that “recent advances in understanding of the contribution of prostaglandin metabolism to vascular wall health suggest that some of the beneficial effects of niacin may well result from activation of the same pathways responsible for the adverse [the flush] reactions. The purpose of this review is to emphasize that the search for agonists that show higher tolerability must take into account all aspects of signaling [by prostaglandin D2] through this [the DP1] receptor.”

  • Niacin: a re-emerging pharmaceutical for the treatment of dyslipidaemia.Br J Pharmacol. 158:429-41 (2009).

In another review paper (Song, 2013), the authors conclude that while the pursuit of a more tolerable form of niacin with some benefits that might add to statins might be attractive to a commercial sponsor, “Such pragmatic reasoning may drive the progressive abandonment of niacin, a drug that has long been a mainstay of cardiovascular therapy, while we still poorly understand its many potentially relevant mechanisms of action and have an incomplete picture of its clinical utility.” (Hear, hear!)

  • Song and FitzGerald. Niacin, an old drug with a new twist. J Lipid Res.54(10):2586-94 (2013).

A further review of niacin in its various forms (McCay, 2012) notes that “[w]hether other compounds that are converted to NA [nicotinic acid] or that contains NA, nicotinamide (NM) or their releasable moieties should be referred to as ‘niacin’ depends on the biological effects that are attributed to the compound, the interpretation of the evidence for the rates of uptake and metabolism, and/or the release of the chemical components (apparent bioavailability) that produce biological effects similar to the primary forms of niacin.”

  • MacKay, Hathcock, Guarneri. Niacin: chemical forms, bioavailability, and health effects. Nutr Rev.70(6):357-66 (2012).

LIVER TOXICITY

This review (McCay, Hathcock, Guarneri, 2012) noted that in the matter of LIVER TOXICITY, “[m]any severe reactions to NA, especially liver toxicity, have involved ill-advised or uninformed switching from NA preparations to ER-NA formulations without adjusting the dose.” That is, the same dose of niacin exhibits a greater risk of liver toxicity in the ER form. We suspect that this is caused by the loss of the PGD2 acutely released by plain niacin which in the ER form is more of a chronic release of PGD2, hence reducing the flushing effect but with the differences we have described in the body of this article above from an anti-inflammatory effect of acutely released PGD2 to a pro-inflammatory effect of chronically elevated levels of PGD2. John Hathcock, a co-author of this review, was formerly a prominent extensively-published scientist at the FDA who is an expert on matters of toxicity, writing frequently on toxicity issues involving nutrients. Dr. Hathcock left the FDA to become a scientist and analyst at the Council for Responsible Nutrition.

  • (McCay, Hathcock, Guarneri 2012 reference in paragraph above)

MORE ON STUDIES OF “EXTENDED RELEASE”
AND “PROLONGED RELEASE” VS. IMMEDIATE
RELEASE NIACIN

It was a surprise to us that in their review discussed just above (McCay, Hathcock, Guarneri, 2012), the authors stated their belief that “the beneficial lipid lowering effects of both NA [nicotinic acid] and ER-NA [extended-release nicotinic acid] are well established with data showing reduction of total triglyceride levels by 20-50%, reduction of LDL-C levels by 10-25%, increases of HDL-C by 10-30% and reduction of lipoprotein a levels by 10-30% which includes preferential reduction of the more atherogenic, small dense LDL-C” as the data we have seen do not tend to support an equivalent effect on lipid levels between NA and ER-NA. As to the declaration of interest for this review, the authors simply note that McCay and Hathcock are “employed by The Council for Responsible Nutrition, a trade association representing dietary supplement manufacturers and ingredient suppliers.” Hence, we do not know why they came to this conclusion, telling us only that they did an extensive search of the literature.

In our own search, we found a number of papers reporting discrepancies between immediate or extended-release niacin with that of immediate-release niacin on lipid lowering that we found to be convincing that there was no such equivalence. For example, a study (Usman, 2014) showed that extended-release niacin could suppress post-meal triglyceride levels but unlike immediate release niacin, it had to be administered just before the fat-containing meal. NON-FATAL MYOCARDIAL INFARCTIONS, as the authors of that study (Usman, 2014) explained “[t]his disparity is relevant because extended-release niacin dominates clinical use, even though only immediate-release niacin prevented hard cardiovascular outcomes.” The authors went on to describe another study (Plaisance, 2008) in which the researchers found that bedtime dosing of <1500 mg extended-release niacin for six weeks failed to suppress postprandial (after meal) triglycerides the next day, unlike immediate-release niacin. The Plaisance et al study, however, involved repeated (that is, chronic) use of niacin over six weeks, whereas the Usman et al study was just for a single dose and the pattern of suppression of triglycerides, the Usman group suggested, depended on post-dose pharmacodynamics, referring to “disappointing cardiovascular effects of bedtime extended-release niacin …”

The paper by other authors (Vogt, 2007) showed that prolonged-release niacin (in this paper they used Niaspan) did increase HDL but not as effectively as immediate-release niacin and that only immediate-release niacin had been shown to reduce cardiovascular event rates.

  • Usman, Qamar, Gadi, et al. Extended-release niacin acutely suppresses postprandial triglyceridemia. Am J Med.125(10):1026-35 (2012).
  • Plaisance, Mestek, Mahurin, et al. Postprandial triglyceride responses to aerobic exercise and extended-release niacin. Am J Clin Nutr.88(1):30-7 (2008).
  • Vogt, Kassner, Hostalek, et al. Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study. Vasc Health Risk Manag.3(4):467-79 (2007).

SCHIZOPHRENIA AND THE NIACIN FLUSH

It is curious to note that a blunted flushing response to niacin has been observed in most schizophrenics, and even in a significant portion of first-degree relatives of schizophrenics (Shah, 1999), “suggest[ing] that niacin subsensitivity is a genetic trait …” (Messamore, 2003). A later paper by the same lead author (Messamore 2010) on niacin sensitivity and the arachidonic acid pathway in schizophrenia reported that, in a study of 20 schizophrenic adults compared to 20 controls, “[t]he schizophrenia-associated niacin response abnormality involves both diminished sensitivity and reduced efficacy.” This supports the possibility that the niacin flush plays a significant role in the clinical effects of niacin.

  • Shah, Ramchand, Peet. The niacin skin flush test: first-degree relatives show responses intermediate between patients and controls. Schizophr Res.38:314 (1999).
  • Relationship between the niacin skin flush and essential fatty acids in schizophrenia. Prostaglandins Leukot Essent Fatty Acids. 69:413-9 (2003).
  • Messamore, Hoffman, and Yao. Niacin sensitivity and the arachidonic acid pathway in schizophrenia. Schizophr Res.122(1-3):248-56 (2010).

A HUMAN STUDY OF DIETARY NIACIN AND THE
RISK OF INCIDENT ALZHEIMER’S (Morris, 2003)

Here, it was reported that, in a group of 3718 participants of 65 years and older residents of a Chicago community, evaluated through the use of dietary data and at least two cognitive assessments to detect cognitive changes over a median 5.5 years, higher food intake of niacin was associated with a slower annual rate of cognitive decline. The authors of this study reported in two case control studies conducted by others that there were lower blood levels of a nicotinic acid metabolite among demented patients than among age and sex matched controls. The detection of such a difference in cognitive changes in individuals ingesting such small amounts of dietary niacin is really surprising, as the participants in the highest fifth of intake (with a median of 22.4 mg/day) had an 80% statistically significant reduction in risk compared with the lowest quintile (12.6 mg/day). These authors attempted to determine whether there was a difference in participants with an apoE4 allele, but could not detect any. At these levels of niacin, it is hard to imagine it would be possible to measure such a small difference.

  • Morris, Evans, Bienias, et al. Dietary niacin and the risk of incident Alzheimer’s disease and of cognitive decline. J Neurol Neurosurg Psychiatry. 75:1093-9 (2004).

Sandy Shaw Copyright 2015

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

October 2017 Breast Health Awareness Education and Prevention are the key to Good Health!

breast cancer awareness handsOctober is a special month for us at Life Priority because it’s our company’s 19th birthday.  Thanks to loyal customers who trust us, we have been able to help thousands of people live happier and healthier lives.  October is also special as it is Breast Health Awareness month.  To celebrate, Life Priority is offering specials on our products that promote breast health.

One-Per Meal Lifeguard is a multivitamin to be taken with each meal that provides nutritional and immune support. One-Per Meal is the foundation to build a healthy and active lifestyle.

Omega-3 Priority™ is a concentrated, USP verified, pharmaceutical-grade fish oil product that offers 400 mg of EPA and 200 mg of DHA in each capsule. Omega-3 fatty acids may help lower the risk of chronic diseases such as cancer, heart disease and arthritis, and are important for cognitive and behavioral function.

Lift/Lift Caps™ helps to eliminate mental fatigue and naturally jump starts your day, without the excess caffeine from energy drinks and countless cups of coffee.

3-Way Calcium Complex™ offers three different sources of calcium for high bioavailability and absorption – meaning they reach one’s bones quicker and are utilized more effectively to strengthen those bones to continue doing what you love most.

IN ADDITION TO OUR PRODUCTS ON SPECIAL, HERE ARE 8 EASY WAYS TO SUPPORT GOOD BREAST HEALTH:

1. Don’t Smoke

2. Exercise

3. Eat more fruits & veggies

4. Maintain a healthy weight

5. Get regular breast cancer screenings

6. Give yourself a monthly breast exam

7. Develop a good “attitude”

8. Take Life Priority vitamins to compliment your diet

To your health,

Michelle & Greg Pryor

 

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

 

Restless Legs A Personal Observation by Sandy Shaw

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 7 • November 2015


RESTLESS LEGS

PERSONAL OBSERVATIONS

by Sandy Shaw

My experience with restless legs finds that, at least in my case, it can be brought on or made worse by:

1. Drinking carbonated beverages—Carbon dioxide inhalation can induce arousal by activating serotonin receptors (Richerson, 2004). Certain serotonin receptors surprisingly, induce arousal. “It is now clear that 5-HT [serotonin] actually causes arousal.” (Richerson, 2004, pg. 451) “Serotonergic neurons in the midbrain are also chemosensitive, and might mediate non-respiratory responses to increased carbon dioxide, such as arousal.” (Richerson, 2004) This arousal may be what drinkers of carbonated beverages are looking for. I find that drinking carbonated beverages increases my symptoms of restless legs. How serotonergic activation would do that I do not know. It is known that serotonin receptors can be involved in motor control (Richerson, 2004). The absorption of carbon dioxide from drinking carbonated drinks may be modulated by taking GAS-X or similar remedy to cause the carbon dioxide gas to be “burped” out, reducing the amount that is absorbed in the gastrointestinal tract. (There has to be a reason why humans go to the trouble and expense of getting carbon dioxide into so many drinks. Yes, it is pleasurable, but why? It may have a stimulating effect to increase awareness and arousal via serotonergic receptors. There may be, however, other chemoreceptors involved in the arousal response to carbon dioxide. See (Buchanan, 2010).

2. Eating foods on an empty stomach when the food contains more than about 20 grams of sugar (sucrose). This may be due to the release of insulin and subsequent release of noradrenaline (Watson, 2006). “Thus, changes in insulin levels may modulate synaptic NE [norepinephrine/noradrenaline] levels and behaviors normally associated with noradrenergic activity.” (Watson, 2006). Although noradrenaline levels decrease with aging, there is the possibility of compensatory hypersensitivity (increased reactiveness to NE). (Ah, yes, it is a delicate balancing act to get the dose of noradrenaline just right.)

Eating sugar with a meal should reduce the likelihood of stimulating restless legs because of the dilution of the sugar and the consequent slower absorption of it. Good sweeteners that avoid insulin release include erythritol (unlike other sugar alcohols, doesn’t cause diarrhea), xylitol, other sugar alcohols, palatinose (a natural sugar, found in honey and sugar cane). These slowly releases sugar for a very low glycemic index effect and little increase in insulin). Synthetic sweeteners such as saccharin, aspartame, sucralose, and others have been shown to have a detrimental effect on the gut microbiota. Stevia may also have similar detrimental effects. See below for article on the potential adverse effects of various non-sucrose sweeteners, both natural and synthetic.

3. I speculate (this is purely a speculation) that restless legs may be a symptom of temporal lobe epilepsy (Ottoson, 2015), which I have, and the symptoms of which increase in my own case concurrently in response to the same inducing factors, such as #1 and #2 above. Moreover, the drugs and nutrients I use to control temporal lobe epilepsy, such as gabapentin (with GABA receptor inducing effects), glycine, and taurine, also are effective in controlling restless legs in my case. The latter are personal observations only. I make no claim of cause and effect or generalizability.

4. Drinking very cold drinks can bring it on in my case, perhaps due to adrenergic stimulation. (Rossato, 2014) “In vivo cold sensation is detected by specific sensors for cold temperature expressed on peripheral cutaneous nerve endings leading to adrenergic stimulation.” (Rossato, 2014) (There has to be a reason why humans prefer very cold drinks and throughout history have gone to great lengths and expense to get what is necessary (refrigeration, ice, deep storage in the earth, etc.) to get their drinks cold. One has to presume that there is a preferred psychopharmacological state. I think it may be, in this case, adrenergic activation (Rossato, 2014) —and/or possibly cholinergic activation—by very cold-detecting sensors in the mouth or gastrointestinal tract. People like the effects of being stimulated.)

“The effect of adrenoceptors agonists on the production of other important mediators involved in inflammation have also been investigated. Prostaglandins are produced via the metabolism of AA [arachidonic acid] by a cyclooxygenase (COX) and subsequently by prostaglandin synthases.” “Our laboratory has also demonstrated that NE [norepinephrine, noradrenaline] is able to increase COX-2 expression in LPS-stimulated microglia.” (Schlachetzki, 2010). LPS is lipopolysaccharide, a bacterial cell wall component that activates the immune system and its inflammatory effects. However, noradrenaline levels decline with aging, a detrimental effect on cognition (Schlachetzki, 2010). Clinical trials treating patients with dementia or cognitive impairments with beta adrenergic receptor blockers has resulted in both beneficial results and detrimental results. In other studies, increasing noradrenaline by treatment with insulin resulted in improvement cognition in demented patients but in another study increased the level of inflammatory markers in the CSF (cerebral spinal fluid). The data are conflicting at this point (or as of 2010).

References

  • Buchanan, Richerson. Central serotonin neurons are required for arousal to CO2. Proc Natl Acad Sci U S A. 107(37):16354-9 (2010).
  • Ottosson, Wu, Nolting, et al. Resin-acid derivatives as potent electrostatic openers of voltage gated K channels and suppressors of neuronal excitability.Sci Rep. 5:13278 (2015). “Many diseases that affect a large number of people, such as epilepsy, cardiac arrhythmia, and chronic pain, depend on increased electrical excitability.” Restless legs is a disorder that clearly involves increased electrical excitability.
  • Richerson. Serotonergic neurons as carbon dioxide sensors that maintain pH homeostasis. Nat Rev Neurosci. Jun;5(6):449-61 (2004).
  • Rossato, Granzotto, Macchi, et al. Human white adipocytes express the cold receptor TRPM8 which activation induces UCP1 expression, mitochondrial activation and heat production. Mol Cell Endocrinol. 183:137-46 (2014).
  • Schlachetzki et al. Function of norepinephrine in neuroinflammation and chronic neurodegenerative diseases. In Biochemistry and Histocytochemistry … Ch. 1. Edited by Fuchs and Auer. Hauppauge NY: Nova Science Publishers, Inc. 2010.
  • Watson, Bernhardt, Reger, et al. Insulin effects on CSF norepinephrine and cognition in Alzheimer’s disease. Neurobiol Aging. 27:38-41 (2006).

 

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

A Hypothesis About Alzheimer’s Disease, Its Cause and a Possible Method of Treatment, and Experimental Support for the Hypothesis by Sandy Shaw

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 6 • October 2015life-extension-book

A Hypothesis About Alzheimer’s Disease, Its Cause and a Possible Method of Treatment, and Experimental Support for the Hypothesis

by Sandy Shaw

One hypothesis shared by me and probably some others about AD is that it is the ultimate dissociative disorder, with the connections between various areas of the brain being destroyed, leaving behind the originally connected material (memories, stored data, etc.), in a state where it cannot be accessed by other brain areas (some scientists including myself wonder whether it might theoretically be possible to reconstruct the connections and retrieve this material. If that is possible, it is likely, I think, to be limited to a certain critical period of time as neurons die when they are not active.)

If the hypothesis is correct, then one prediction is that the restoration of connections in a model of cholinergic denervation might be a reasonable model for Alzheimer’s disease and a possible correction. Thus, a 2010 paper (Kampen and Eckman, 2010) is right on point. Here, the researchers studied the use of cholinergic agonists to restore hippocampal neurogenesis and improve cognition in a model of cholinergic denervation (the very connections the hypothesis would suggest are missing or damaged). The authors report “the effects of various cholinergic compounds on indices of hippocampal neurogenesis, demonstrating a significant induction following pharmacological activation of [cholinergic] muscarinic M1 receptors, located on hippocampal progenitors in the adult brain [of female Sprague-Dawley rats].” The chemicals studied included nicotine (which is an agonist, that is, it activates, nicotinic-cholinergic receptors and the cholinesterase inhibitor physostigmine, the nonselective cholinergic agonist carbachol, the muscarinic agonist oxotremorine, or their vehicle.

Results showed that the maximal induction was observed following the highest dose of oxotremorine, the muscarinic agonist. Only lower doses of carbachol elevated cell proliferation in the dentate gyrus (an area of neurogenesis), and the CHOLINESTERASE INHIBITOR physostigmine triggered a modest, but significant, elevation in the production of new neurons from progenitors. As the authors explain, “…we have shown that selective activation of muscarinic receptors is capable of triggering an induction of cell proliferation not only in the DG [dentate gyrus], but also the CA1 region of the hippocampus, an area of severe neuronal loss in AD [Alzheimer’s disease].” “…oxotremorine-induced increases in BrdU-positive cell counts [neurogenic cells] are likely to reflect an effect on cell proliferation rather than an indirect effect on cell survival.” “…impairments in cell proliferation, in a model of basal forebrain cholinergic cell loss are counteracted by chronic muscarinic activation. This restoration of cell proliferation is accompanied by a time dependent increase in the number of newly generated cells expressing neuronal markers and by a reversal of cognitive deficits characteristic of this model.”

  • Kampen, Eckman. Agonist-induced restoration of hippocampal neurogenesis and cognitive improvement in a model of cholinergic denervation.Neuropharmacology. 58:921-9 (2010).

 

www.lifepriority.com 800-787-5438

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

Greg Pryor: Fighting the Stress of Post Season Baseball

KC Royals 1985 World Series Win

KC Royals 1985 World Series Win

After I attended my first MLB game in Cleveland, Ohio as a 7-year-old, I became “addicted” to baseball.  Fortunately I was able to spend 16 seasons as a professional player (5 seasons for the Kansas City Royals).  I have experienced the depths of stressful feelings that baseball can create, on and off the field.  Last season, all KC Royals fans were treated to one of the best postseason runs in baseball history.  I noticed a resurgence of incredible love for Royals baseball from thousands of “veteran” fans and new ones.

We were constantly on the edge of our seats during the month of September and October as we lost work time and sleep!  Some of us forgot what day of the week it was! From the glorious night of last season’s Wild Card game versus the Oakland A’s to the last out of the World Series….WE FELT STRESSED!

The ’15 Royals team has been so much fun to watch from spring training to the inevitable day we clinched our first American League Central Division title since 1985! We are thinking ahead of who our opponents might be in the Division playoffs, and, hopefully, the American League championship and World Series game. Again, it is STRESS time for many Royals fans!

As a co-owner of a health and nutrition company for the past 20 years (lifepriority.com), this is a great time to inform you about how stress affects us and offer some information that might help increase your natural defense systems to deal with the stress in our lives, especially all Royals fans!

Stress is the body’s natural response to threatening situations, and it affects everyone. Stress can be good, like buying a

brainnew car, or bad, like running up credit cards. Either way, your body and mind react to such situations with a heightened state of readiness, which is called the “fight or flight” response. This reaction causes your brain to make hormones including adrenaline and cortisol.

Adrenaline gives you more energy by increasing your heart rate and blood pressure.  Cortisol increases the amount of glucose in your blood and impairs bodily functions that might be harmful in a fight or flight situation, such as digestion and reproduction. This can help you perform well on a test or at a sporting event, but it can also distract you, keep you up at night, and make you lose your appetite.

Stress becomes chronic when your body does not shut off its stress response, so you are always in a heightened state of readiness.  This affects your immune system and can lead to mental and physical health problems.

One of the ways that you can defend yourself is to make sure that you provide your body with stress-reducing nutrients through your diet. To ensure that your diet provides you with enough of those nutrients, you should consider supplementing your diet with a potent, high-quality multi-vitamin with adequate amounts of B vitamins, vitamin C, vitamin D3, and omega-3 fatty acid. Life Priority offers the following products that allow you to touch all of your nutritional bases so put them into your daily nutritional “lineup”: One Per Meal Lifeguard, Sunlife, Omega-3 Priority, Vita C2, Lift and Mind.  Read about these great products and other Life Priority products at www.lifepriority.com today!

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.
*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.