Tag Archive : life extension

Greg Pryor – September 2018 Men’s Health!

September Celebrates of Men’s Health!

In today’s fast-paced lifestyles, most men are faced with increasing mental and physical demands as they age. Personally, I have found that an easy, logical way to slow up my aging process is to keep my body and brain more fit through the use of a few essential supplements with each meal.

I urge all men to consider, at least, the use of the following supplements:

  •  Lifeguard-a high-quality multivitamin created to try and help to provide immune support and fill in the gaps of your diet,
  •  Omega-3 Priority™-a potent omega-3 supplement for heart (EPA) and brain health (DHA),
  • Prostate Priority™ specific nutrients that may help promote a healthy prostate,
  •  Joint Decision™ or Total Joint Complexglucosamine that may help to support and maintain healthy cartilage health.

I feel that the consistent, daily use of the right nutrients in supplement form (and in adequate amounts!) is one of the most important health decisions that we can make. Based on the past 20 years of being in the dietary supplement industry through my company, Life Priority, and my 16 year career as a pro athlete, I feel strongly that using high-quality supplements is imperative. Your diet is most likely lacking in one or more essential nutrients. You can help yourself feel better and slow up your personal aging process by using high-quality supplements.

In addition, men are at increased risk for heart related issues including heart attack and cardiovascular disease. They are also at a higher risk for prostate cancer. Both heart disease and prostate cancer affect millions of men every year and take many away from their families and friends too soon. If men can incorporate more exercise, consume more fish with essential fatty acids (EFA’s), visit their doctors regularly and watch out for depression and high blood pressure, stop smoking and use a daily multivitamin, they can increase their life expectancy and live healthier, fuller lives.

I have been involved as a retail customer or a marketer of dietary supplements since 1991.  Don’t leave your physical and mental well-being up to anyone else! It’s your life! Your body, including your brain, is aging each day and you can give yourself a better chance at living a healthier (and happier!) life by simply using enough of the right nutrients each day with meals or at bedtime.

I helped form Life Priority, Inc. in 1994 to secure the nutritional products I wanted for my own personal use.  A major reason that Life Priority was formed was because of the research of 2 scientists who were the co-authors of a NY Times best-seller Life Extension, A Practical Scientific Approach, which was written specifically for doctors. The authors, Durk Pearson and Sandy Shaw, wrote Life Extension so that doctors could understand how using certain nutrients in adequate amounts could slow up the aging process.

To Your Health!

Greg Pryor-Life Priority President, Co-Founder and  #1 Customer

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.

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.

Time Is On My Side-LEF News Sandy Shaw

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 20 No. 2 • March 2017


TIME IS ON MY SIDE … YES, IT IS

by Sandy Shaw

The difference between drug use and addiction or eating and metabolic diseases is time. The amount of time we take a potentially addictive drug determines whether we become addicted; this is also true for eating—eating for only a limited period of time can prevent the development of metabolic diseases, such as diabetes type 2 (Hatori, 2012).

An example of how time can determine the result of eating: a recent study of male mice fed a high fat diet found that restricting feeding to only eight hours a day WITHOUT REDUCING CALORIES as compared to being free to eat at any time prevented metabolic diseases (such as obesity, hyperinsulinemia, fatty liver, and inflammation).

Dopamine is required for the estimation of time by the internal clock. “Interval timing, the ability to discriminate durations in the seconds-to-minutes range, is a form of temporal cognition that requires an optimal level of dopaminergic function in cortico-striatal circuits in order to control time sharing and regulate clock speed.” A time interval is initiated by cortical oscillators in the ventral tegmental area of the brain by a burst of dopamine accompanied by a burst of theta power, which act as the “start gun” (Kononowicz, 2015).

The internal clock is critically controlled by dopaminergic agonists and antagonists. Dopamine agonists such as cocaine and methamphetamine (“speed”) have been shown to increase the speed of the internal clock, while dopamine antagonists such as haloperidol and raclopride have been shown to decrease the speed of the internal clock (Cheng, 2007).

In another study (Sysoeva, 2010), researchers found that there is an association of serotonin (5-HT) related genes with time perception. In their experiment, forty-four Russian Caucasian males (right handed and with a mean age of 22) compared two durations (they had to indicate which of them was shorter) on a computer monitor. “Many studies have reported an association between duration representation parameters and personality, specifically impulsivity and psychoticism.” Unsurprisingly, other studies have found psilocybin, a 5-HT (serotonin) receptor agonist, to affect time perception (Sysoeva, 2010).

“Despite the evidence … suggesting the centrality of DAergic [dopaminergic] modulation in mediating the drug-induced euphoria and timing distortions reported here, this explanation is likely an oversimplification of the processes underlying the individual differences observed in this study. Neuromodulators such as serotonin, GABA, glutamate, and norepinephrine, have also been found to influence time perception and to interact with DA [dopamine] in complex ways (Lake, 2013).” Another neuro­transmitter with important effects on drug addiction and incentive-motivated behaviors is acetylcholine (Lester, 2010).

WHEN TIME SLOWS DOWN

You’ve all experienced it—the times when sudden danger appears, such as your car is about to hit a tree, and time slows release of adrenaline as you rapidly close in on the tree. As explained above, stimulants such as methamphetamine cause a large release of dopamine and this increases the speed of the internal clock. A hypothesis proposes that the reason this feels like time is slowing down is that your brain sees time as the amount of information it processes—the more bits of information is counted as a longer period of time compared to the usual number of bits you experience as “regular” time (Eagleman, 2005).

In a similar fashion, seeing an event in “slow motion” causes observers to believe that more time had passed than actually had (Caruso, 2016). Thus, time is under­estimated.

A very recent paper (Soares, 2016) reported how mice judged the passage of time (judging the duration of intervals). Using a pharmacogenetic method to suppress dopaminergic neuronal activity in the substantia nigra pars compacta, they found that “[s]ituations in which DAergic [dopaminergic] activity is elevated naturally, such as states of high approach motivation, response uncertainty, or cognitive engagement are associated with underestimation of time. Conversely, situations that decrease DAergic activity, such as when fearful or aversive stimuli are presented are associated with overestimation of time.”

The bottom line: “… pleasurable events boost dopamine release, which should cause your internal clock to run faster … so that short intervals seem longer than they are (Simen, 2016).”

FLOW

Time stands still if you go fast enough.

—Stephen F. Kaufman, marial arts professional (Ch.
19 in his book “The Way Of The Modern Warrior”)

Who hasn’t experienced FLOW? The trick is being able to produce it when you want it.

Flow is often described as a state of effortless concentration so deep that people who experience it lose their sense of time. It gives you a sense of acting without conscious awareness, of time slowing down, of perceiving yourself to be moving through a dreamlike state.*


Szxycj at English Wikipedia

We knew a highly skilled champion racecar driver (Mickey Thompson) who told us that using a BLAST family formulation of ours had, in a very long off-road auto race (the BAJA 1000, when it was 1000 miles rather than 1000 kilometers) resulted in time slowing down, with everything happening exactly right and without any conscious effort on his part. He said that it felt like the flow he had experienced in his best races.

The formulation that Mickey took was one of those we designed for our own use that contains the amino acid phenylalanine. Phenylalanine can be converted into tyrosine (which is then converted to dopamine) but also into phenethylamine (also called phenylethylamine), a neuromodulator that provides mental energy like caffeine, but also acts as a stimulus barrier (helps to filter out distractions). Phenylalanine is found in our BLAST formulas.

Caffeine provides mental energy in a different way than phenylalanine (see above). Phenylalanine is a natural compound that increases dopamine (via conversion to tyrosine) but, unlike caffeine (a xenobiotic), it does not mimic the effects of amphetamine and cocaine, like caffeine can do at 4-5 times the average human consumption of coffee. At high doses (300-800 mg), caffeine can increase feelings of anxiety, nervousness, and insomnia. Caffeine does NOT have addictive potential at the usual level of human consumption (50-300 mg or 1-3 cups of coffee), but induces feelings of well-being, alertness, energy, and ability to concentrate. Most of the effects of caffeine are reported to take place at adenosine receptors, where caffeine is an inhibitor (Nehlig, 2000). There are other changes, though, which include a 26-30% increase in the densities of cortical muscarinic and nicotinic cholinergic receptors; the evidence supports significant alterations in adenosine, adrenergic, serotonergic cholinergic, and GABAergic systems (Shi, 1993).

NUTRIENTS THAT MODIFY THE SPEED OF THE INTERNAL CLOCK

The amino acid tyrosine is precursor to dopamine, that is, converted to dopamine. (The amino acid phenylalanine is converted to tyrosine, so it is an indirect precursor to dopamine.) As noted above, dopamine agonists increase the speed of the internal clock (Cheng, 2007; Meck, 1987). This feels like time is slowing down. (Interestingly, “flow” is a process in which time does feel as though it is slowing down.)

WHEN PLEASURE BECOMES A HABIT

In the scientific literature, addiction is often called habit formation. Habit formation differs immensely from goal-directed activity. Where goal-directed activity is influenced by the outcome of performing an action, addictive activity is not—a negative outcome does not influence it.** If an action is habitual, “then devaluation should have no effect on performance, since habits are elicited by antecedent stimuli which are not affected by devaluation. “… habitual behavior is not controlled by the action-outcome contingency … (Yu. 2009)”

This can be seen in lever pressing by experimental animals. “At first lever pressing is goal-directed and sensitive to manipulation like outcome devaluation. Under certain conditions, it can become more habitual and impervious to changes in the value of the outcome … Studies in flies, mice, rats, horses, monkeys, and humans have shown some version of this transition from more flexible and goal-directed behavior to inflexible and habitual behavior.” (Yu, 2009)

It was purely the feeling that had captivated me, made me sacrifice everything to it, gladly, joyfully. It was a seashell’s pristine whisper in my ear, warm sun rising in my heart, fireflies winking in the nerves.

—Will Bohnaker, Haunts of The Aardwolf, on the allure of caffeine

EATING: DELAY DISCOUNTING

A recent paper (Johnson, 2010) points to a proposal that “deficits in reward processing may be an important risk factor for the development of obesity, and that obese individuals may compulsively consume palatable food to compensate for reward hyposensitivity.” This is another way of saying “self-medication.”

The dopaminergic nervous system is critically involved in the perception of pleasure from eating and sex. In fact, “the degree of pleasure from eating correlates with [the] amount of dopamine release (Stice, 2008).” The chronic overeating of high fat and high sugar foods causes a decrease in the sensitivity of dopaminergic neurons as a result of downregulation (reduced signaling). Animal studies have found similar effects from overeating and also in response to chronic drug use. Both overeating and the use of addictive drugs cause downregulation of dopamine D2 receptors and decreased D2 sensitivity.

A deficiency in the release of dopamine in the dorsal striatum may also be seen in individuals with a certain variant (allele) of the D2 dopaminergic receptor gene, the Taq1A A1 allele; it is interesting to note that this allele is involved in impulsivity, which is defined as “the relative preference for a smaller reward, sooner in time, compared to a larger reward, later in time … (Eisenberg, 2007)” This is called delay discounting—and “non-human research suggests that corticostriatal mesolimic substrates mediate delay discounting performance and that dopamine is the critical neurotransmitter involved.” (Eisenberg, 2007) The famous marshmallow experiments were a particularly notable example of delay discounting.

MONOAMINE OXIDASE A (MAOA) AND IMPULSIVITY

Monoamine oxidase A (MAOA) is a gene importantly affecting impulsivity. “… the risk imparted by the specific genetic variation studied here [MAOA] contributes to the impulsive dimension of this complex behavior [aggression].” The monoamine oxidase A (MAOA) gene, is of two types—MAOA-L (the low expression variant) and MAOA-H (the high expression variant). MAOA-L is associated with an increased risk of violent behavior. “Arguably, the clearest link between genetic variation and aggression exists for monoamine oxidase A (MAO-A) … a key enzyme in the catabolism [breakdown] of monoamines, especially serotonin.” The enzyme catabolizes dopamine, serotonin, and norepinephrine, reducing their availability for signaling at neuronal synapses (Meyer-Lindenberg, 2006). Hence, reduced catabolism, as with the MAOA-L variant, will not decrease the availability of dopamine, serotonin, and norepinephrine for signaling as much as the MAOA-H variant.

Goal-directed dimensions of aggression have been associated with psychopathy, often accompanied by diminished empathy and remorse. In their study (Meyer-Lindenberg, 2006), the researchers found that “men, but not women, carrying the low-expression MAOA genotype showed increased [emotional] reactivity during retrieval of negatively valenced emotional material.” Interestingly, men have only one allele (copy) of the MAOA gene, whereas women have two. The reason for this is that men have only one X chromosome (where the MAOA gene is located), while (of course) women have two. Interestingly, estrogens have been shown to affect the expression of MAOA in the brain (Meyer-Lindenberg, 2006).

Higher dominance has been associated with the low expression variant of MAOA (MAOA-L) and aggression in males in studies of primates.

SEROTONIN AND IMPULSIVITY

As noted above, serotonin deficiency is associated with impulsive behavior. This can be corrected by taking tryptophan, the amino acid that is converted to 5-hydroxytryptophan by the enzyme tryptophan hydroxylase and then to serotonin. However, some individuals are unable to make this conversion in sufficient amounts because their version of the enzyme lacks adequate potency. A way to overcome this is to take 5-HTP (5-hydroxytryptophan), which bypasses the need for tryptophan hydroxylase. We suggest taking 25 to 50 mg of 5-HTP at bedtime. We get ours from our Serene Tranquility with 5-HTP.™

DELAY DISCOUNTING MEETS THE GRASSHOPPER AND THE ANT


The Ant and the Grasshopper

Another experiment on delay discounting (like the marshmallow experiments) was performed in human subjects, who made a series of choices between early and delayed monetary rewards while they were examined by fMRI (functional magnetic resonance imaging) (McClure, 2004). As a result, the researchers developed a hypothesis for how the brain decides between the early and later rewards. “… we hypothesize that short-run impatience is driven by the limbic system, which responds preferentially to immediate rewards and is less sensitive to the value of future rewards, whereas long-run patience is mediated by the lateral prefrontal cortex and associated structures, which are able to evaluate trade-offs between abstract rewards, including rewards in the more distant future.”

They allude to the metaphor of the grasshopper and the ant. The grasshopper spends its time enjoying the present and ignoring what may come later, while the patient ant works diligently preparing for the future. The authors call delay discounting the competition between the “impetuous limbic grasshopper” and the “provident prefrontal ant.” (McClure, 2004).”

In sum, the researchers suggest that “human behavior is often governed by a competition between lower level, automatic processes that may reflect evolutionary adaptations in particular environments, and the more recently evolved, uniquely human capacity for abstract, domain-general reasoning and future planning.”

Another hypothesis on the neuro­chemistry of delay discounting (Kravitz, 2012) proposes that addiction (in which the future consequences of using drugs are ignored) depends upon the interaction between dopamine D1 receptors and dopamine D2 receptors: dopamine D2 receptors counteract dopamine D1 receptors in determining the probability of performing a future action. The D1 receptors induce persistent reinforcement, while the D2 receptors induce transient “punishment” (negative signaling) for the performance of a future action. “In contrast, depression is marked by impaired reinforcement from positive stimuli and heightened punishment from negative stimuli (Kravitz, 2012).”

SPEAKING OF ANTS …

Yes, speaking of ants, a recent paper appeared in the “Research Highlights” section of the 29 Sept. 2016 Nature which reported that ants can get hooked on morphine. The ants were given access to sugar water laced with morphine. Then, over the course of several days, the amount of sugar in the water was reduced while the morphine content was increased, until eventually there was NO sugar in the water, only morphine. The ants, given a choice between sugar water and the sugar-free morphine solution, preferred the sugar-free morphine by 65% to 35%. Plus the ants’ brains showed elevated levels of dopamine, just as addicted mammals do. The authors were said to suggest that ants might make a good model for studying addiction in humans. Durk wonders why 35% of the ants DIDN’T choose morphine … Sandy suggests that maybe those ants had a different version of the D2 dopamine receptor.

HIGH IMPULSIVITY PREDICTS THE SWITCH TO COMPULSIVE COCAINE-TAKING

Rats, like humans, can get addicted to drugs. When rats are exposed to cocaine, 15-20% of them become addicted, which is similar to that observed in humans (Belin, 2008).

“… the essential feature of addiction … [is] … the persistence of drug-seeking in the face of negative consequences …” explain researchers in a 2008 paper (Belin, 2008). In their study, they found that high impulsivity “predicts the development of addiction-like behavior in rats … [and they note that, in humans,] … there is a high comorbidity between drug addiction and disorders characterized by impulsive behavior, such as attention deficit-hyperactivity disorder.”

Low serotonin levels are thought to be a cause of impulsivity. For example, reducing serotonin levels by tryptophan-restricted diets results in more impulsive choices in experiments. A recent paper (Bevilacqua, 2010) found that a mutation in the serotonin 2B receptor predisposed a Finnish population to severe impulsivity.

Lithium may reduce impulsivity, but studies reporting this association have involved doses much higher than the low-dose form that we use. One such study (in rats) found that a “moderate” dose of lithium (20 mg/kg) suppressed impulsive behavior (Ohmura, 2012). Research involving the low concentrations of lithium found in mineral waters and in some tap water has reported reduced impulsiveness and suicide in people.

Another way to reduce impulsivity is to take tryptophan (precursor to serotonin). See above in “Eating: Delay Discounting.”

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 For Pain: Sickle Cell Disease

The Durk Pearson & Sandy Shaw®
Life Extension News
Volume 20 No. 2 • March 2017

ARGININE FOR PAIN: SICKLE CELL DISEASElife-extension-book
Normal free-flowing red blood cells versus sickle cells becoming lodged. Preliminary clinical studies are showing promising results in the treatment of pain in patients with sickle cell disease. Pain is the hallmark of sickle cell disease, with some patients in pain all of the time. Arginine has been found in these preliminary clinical studies to be effective against the pain due to vaso-occlusive blood clots. “Phase II clinical trials of arginine therapy for sickle-related pain are underway and a Phase III randomized controlled trial is anticipated in the near future (Bakshi, 2016).”
Sickle cell disease is described as an “arginine deficiency syndrome (Bakshi, 2016).” The “global arginine bioavailability ratio” (GABR) was developed to assess the state of arginine sufficiency as expressed in the ratio of arginine to arginine metabolites (ornithine and citrulline). The GABR is low, not only in sickle cell disease, but also in diabetes. Moreover, a low GABR “has been shown to be a strong predictor of cardiovascular disease and early mortality in general (Bakshi, 2016).”

Arginine can be found in our Muscle Memory™, with each serving containing 6 grams of arginine. Suggested use is 1 to 3 servings a day on an empty stomach—at bedtime, upon awakening, or before exercise.

Reference

Bakshi and Morris. The role of the arginine metabolome in pain: implication for sickle cell disease. J Pain Res. 9:167-75 (2016).

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.

Time Is On My Side….Yes, It Is

The Durk Pearson & Sandy Shaw®life-extension-book
Life Extension NewsTM
Volume 20 No. 2 • March 2017

TIME IS ON MY SIDE … YES, IT IS

by Sandy Shaw

The difference between drug use and addiction or eating and metabolic diseases is time. The amount of time we take a potentially addictive drug determines whether we become addicted; this is also true for eating—eating for only a limited period of time can prevent the development of metabolic diseases, such as diabetes type 2 (Hatori, 2012).

An example of how time can determine the result of eating: a recent study of male mice fed a high fat diet found that restricting feeding to only eight hours a day WITHOUT REDUCING CALORIES as compared to being free to eat at any time prevented metabolic diseases (such as obesity, hyperinsulinemia, fatty liver, and inflammation).

Dopamine is required for the estimation of time by the internal clock. “Interval timing, the ability to discriminate durations in the seconds-to-minutes range, is a form of temporal cognition that requires an optimal level of dopaminergic function in cortico-striatal circuits in order to control time sharing and regulate clock speed.” A time interval is initiated by cortical oscillators in the ventral tegmental area of the brain by a burst of dopamine accompanied by a burst of theta power, which act as the “start gun” (Kononowicz, 2015).

The internal clock is critically controlled by dopaminergic agonists and antagonists. Dopamine agonists such as cocaine and methamphetamine (“speed”) have been shown to increase the speed of the internal clock, while dopamine antagonists such as haloperidol and raclopride have been shown to decrease the speed of the internal clock (Cheng, 2007).

In another study (Sysoeva, 2010), researchers found that there is an association of serotonin (5-HT) related genes with time perception. In their experiment, forty-four Russian Caucasian males (right handed and with a mean age of 22) compared two durations (they had to indicate which of them was shorter) on a computer monitor. “Many studies have reported an association between duration representation parameters and personality, specifically impulsivity and psychoticism.” Unsurprisingly, other studies have found psilocybin, a 5-HT (serotonin) receptor agonist, to affect time perception (Sysoeva, 2010).

“Despite the evidence … suggesting the centrality of DAergic [dopaminergic] modulation in mediating the drug-induced euphoria and timing distortions reported here, this explanation is likely an oversimplification of the processes underlying the individual differences observed in this study. Neuromodulators such as serotonin, GABA, glutamate, and norepinephrine, have also been found to influence time perception and to interact with DA [dopamine] in complex ways (Lake, 2013).” Another neuro­transmitter with important effects on drug addiction and incentive-motivated behaviors is acetylcholine (Lester, 2010).

WHEN TIME SLOWS DOWN

You’ve all experienced it—the times when sudden danger appears, such as your car is about to hit a tree, and time slows release of adrenaline as you rapidly close in on the tree. As explained above, stimulants such as methamphetamine cause a large release of dopamine and this increases the speed of the internal clock. A hypothesis proposes that the reason this feels like time is slowing down is that your brain sees time as the amount of information it processes—the more bits of information is counted as a longer period of time compared to the usual number of bits you experience as “regular” time (Eagleman, 2005).

In a similar fashion, seeing an event in “slow motion” causes observers to believe that more time had passed than actually had (Caruso, 2016). Thus, time is under­estimated.

A very recent paper (Soares, 2016) reported how mice judged the passage of time (judging the duration of intervals). Using a pharmacogenetic method to suppress dopaminergic neuronal activity in the substantia nigra pars compacta, they found that “[s]ituations in which DAergic [dopaminergic] activity is elevated naturally, such as states of high approach motivation, response uncertainty, or cognitive engagement are associated with underestimation of time. Conversely, situations that decrease DAergic activity, such as when fearful or aversive stimuli are presented are associated with overestimation of time.”

The bottom line: “… pleasurable events boost dopamine release, which should cause your internal clock to run faster … so that short intervals seem longer than they are (Simen, 2016).”

FLOW

Time stands still if you go fast enough.

—Stephen F. Kaufman, marial arts professional (Ch.
19 in his book “The Way Of The Modern Warrior”)

Who hasn’t experienced FLOW? The trick is being able to produce it when you want it.

Flow is often described as a state of effortless concentration so deep that people who experience it lose their sense of time. It gives you a sense of acting without conscious awareness, of time slowing down, of perceiving yourself to be moving through a dreamlike state.*
Szxycj at English Wikipedia We knew a highly skilled champion racecar driver (Mickey Thompson) who told us that using a Lift formulation of ours had, in a very long off-road auto race (the BAJA 1000, when it was 1000 miles rather than 1000 kilometers) resulted in time slowing down, with everything happening exactly right and without any conscious effort on his part. He said that it felt like the flow he had experienced in his best races.
The formulation that Mickey took was one of those we designed for our own use that contains the amino acid phenylalanine. Phenylalanine can be converted into tyrosine (which is then converted to dopamine) but also into phenethylamine (also called phenylethylamine), a neuromodulator that provides mental energy like caffeine, but also acts as a stimulus barrier (helps to filter out distractions). Phenylalanine is found in our Lift formulas.

Caffeine provides mental energy in a different way than phenylalanine (see above). Phenylalanine is a natural compound that increases dopamine (via conversion to tyrosine) but, unlike caffeine (a xenobiotic), it does not mimic the effects of amphetamine and cocaine, like caffeine can do at 4-5 times the average human consumption of coffee. At high doses (300-800 mg), caffeine can increase feelings of anxiety, nervousness, and insomnia. Caffeine does NOT have addictive potential at the usual level of human consumption (50-300 mg or 1-3 cups of coffee), but induces feelings of well-being, alertness, energy, and ability to concentrate. Most of the effects of caffeine are reported to take place at adenosine receptors, where caffeine is an inhibitor (Nehlig, 2000). There are other changes, though, which include a 26-30% increase in the densities of cortical muscarinic and nicotinic cholinergic receptors; the evidence supports significant alterations in adenosine, adrenergic, serotonergic cholinergic, and GABAergic systems (Shi, 1993).

NUTRIENTS THAT MODIFY THE SPEED OF THE INTERNAL CLOCK

The amino acid tyrosine is precursor to dopamine, that is, converted to dopamine. (The amino acid phenylalanine is converted to tyrosine, so it is an indirect precursor to dopamine.) As noted above, dopamine agonists increase the speed of the internal clock (Cheng, 2007; Meck, 1987). This feels like time is slowing down. (Interestingly, “flow” is a process in which time does feel as though it is slowing down.)

WHEN PLEASURE BECOMES A HABIT

In the scientific literature, addiction is often called habit formation. Habit formation differs immensely from goal-directed activity. Where goal-directed activity is influenced by the outcome of performing an action, addictive activity is not—a negative outcome does not influence it.** If an action is habitual, “then devaluation should have no effect on performance, since habits are elicited by antecedent stimuli which are not affected by devaluation. “… habitual behavior is not controlled by the action-outcome contingency … (Yu. 2009)”

This can be seen in lever pressing by experimental animals. “At first lever pressing is goal-directed and sensitive to manipulation like outcome devaluation. Under certain conditions, it can become more habitual and impervious to changes in the value of the outcome … Studies in flies, mice, rats, horses, monkeys, and humans have shown some version of this transition from more flexible and goal-directed behavior to inflexible and habitual behavior.” (Yu, 2009)

It was purely the feeling that had captivated me, made me sacrifice everything to it, gladly, joyfully. It was a seashell’s pristine whisper in my ear, warm sun rising in my heart, fireflies winking in the nerves.

—Will Bohnaker, Haunts of The Aardwolf, on the allure of caffeine

EATING: DELAY DISCOUNTING

A recent paper (Johnson, 2010) points to a proposal that “deficits in reward processing may be an important risk factor for the development of obesity, and that obese individuals may compulsively consume palatable food to compensate for reward hyposensitivity.” This is another way of saying “self-medication.”

The dopaminergic nervous system is critically involved in the perception of pleasure from eating and sex. In fact, “the degree of pleasure from eating correlates with [the] amount of dopamine release (Stice, 2008).” The chronic overeating of high fat and high sugar foods causes a decrease in the sensitivity of dopaminergic neurons as a result of downregulation (reduced signaling). Animal studies have found similar effects from overeating and also in response to chronic drug use. Both overeating and the use of addictive drugs cause downregulation of dopamine D2 receptors and decreased D2 sensitivity.

A deficiency in the release of dopamine in the dorsal striatum may also be seen in individuals with a certain variant (allele) of the D2 dopaminergic receptor gene, the Taq1A A1 allele; it is interesting to note that this allele is involved in impulsivity, which is defined as “the relative preference for a smaller reward, sooner in time, compared to a larger reward, later in time … (Eisenberg, 2007)” This is called delay discounting—and “non-human research suggests that corticostriatal mesolimic substrates mediate delay discounting performance and that dopamine is the critical neurotransmitter involved.” (Eisenberg, 2007) The famous marshmallow experiments were a particularly notable example of delay discounting.

MONOAMINE OXIDASE A (MAOA) AND IMPULSIVITY

Monoamine oxidase A (MAOA) is a gene importantly affecting impulsivity. “… the risk imparted by the specific genetic variation studied here [MAOA] contributes to the impulsive dimension of this complex behavior [aggression].” The monoamine oxidase A (MAOA) gene, is of two types—MAOA-L (the low expression variant) and MAOA-H (the high expression variant). MAOA-L is associated with an increased risk of violent behavior. “Arguably, the clearest link between genetic variation and aggression exists for monoamine oxidase A (MAO-A) … a key enzyme in the catabolism [breakdown] of monoamines, especially serotonin.” The enzyme catabolizes dopamine, serotonin, and norepinephrine, reducing their availability for signaling at neuronal synapses (Meyer-Lindenberg, 2006). Hence, reduced catabolism, as with the MAOA-L variant, will not decrease the availability of dopamine, serotonin, and norepinephrine for signaling as much as the MAOA-H variant.

Goal-directed dimensions of aggression have been associated with psychopathy, often accompanied by diminished empathy and remorse. In their study (Meyer-Lindenberg, 2006), the researchers found that “men, but not women, carrying the low-expression MAOA genotype showed increased [emotional] reactivity during retrieval of negatively valenced emotional material.” Interestingly, men have only one allele (copy) of the MAOA gene, whereas women have two. The reason for this is that men have only one X chromosome (where the MAOA gene is located), while (of course) women have two. Interestingly, estrogens have been shown to affect the expression of MAOA in the brain (Meyer-Lindenberg, 2006).

Higher dominance has been associated with the low expression variant of MAOA (MAOA-L) and aggression in males in studies of primates.

SEROTONIN AND IMPULSIVITY

As noted above, serotonin deficiency is associated with impulsive behavior. This can be corrected by taking tryptophan, the amino acid that is converted to 5-hydroxytryptophan by the enzyme tryptophan hydroxylase and then to serotonin. However, some individuals are unable to make this conversion in sufficient amounts because their version of the enzyme lacks adequate potency. A way to overcome this is to take 5-HTP (5-hydroxytryptophan), which bypasses the need for tryptophan hydroxylase. We suggest taking 25 to 50 mg of 5-HTP at bedtime. We get ours from our Serene Tranquility with 5-HTP.™

DELAY DISCOUNTING MEETS THE GRASSHOPPER AND THE ANT
The Ant and the Grasshopper Another experiment on delay discounting (like the marshmallow experiments) was performed in human subjects, who made a series of choices between early and delayed monetary rewards while they were examined by fMRI (functional magnetic resonance imaging) (McClure, 2004). As a result, the researchers developed a hypothesis for how the brain decides between the early and later rewards. “… we hypothesize that short-run impatience is driven by the limbic system, which responds preferentially to immediate rewards and is less sensitive to the value of future rewards, whereas long-run patience is mediated by the lateral prefrontal cortex and associated structures, which are able to evaluate trade-offs between abstract rewards, including rewards in the more distant future.”
They allude to the metaphor of the grasshopper and the ant. The grasshopper spends its time enjoying the present and ignoring what may come later, while the patient ant works diligently preparing for the future. The authors call delay discounting the competition between the “impetuous limbic grasshopper” and the “provident prefrontal ant.” (McClure, 2004).”

In sum, the researchers suggest that “human behavior is often governed by a competition between lower level, automatic processes that may reflect evolutionary adaptations in particular environments, and the more recently evolved, uniquely human capacity for abstract, domain-general reasoning and future planning.”

Another hypothesis on the neuro­chemistry of delay discounting (Kravitz, 2012) proposes that addiction (in which the future consequences of using drugs are ignored) depends upon the interaction between dopamine D1 receptors and dopamine D2 receptors: dopamine D2 receptors counteract dopamine D1 receptors in determining the probability of performing a future action. The D1 receptors induce persistent reinforcement, while the D2 receptors induce transient “punishment” (negative signaling) for the performance of a future action. “In contrast, depression is marked by impaired reinforcement from positive stimuli and heightened punishment from negative stimuli (Kravitz, 2012).”

SPEAKING OF ANTS …

Yes, speaking of ants, a recent paper appeared in the “Research Highlights” section of the 29 Sept. 2016 Nature which reported that ants can get hooked on morphine. The ants were given access to sugar water laced with morphine. Then, over the course of several days, the amount of sugar in the water was reduced while the morphine content was increased, until eventually there was NO sugar in the water, only morphine. The ants, given a choice between sugar water and the sugar-free morphine solution, preferred the sugar-free morphine by 65% to 35%. Plus the ants’ brains showed elevated levels of dopamine, just as addicted mammals do. The authors were said to suggest that ants might make a good model for studying addiction in humans. Durk wonders why 35% of the ants DIDN’T choose morphine … Sandy suggests that maybe those ants had a different version of the D2 dopamine receptor.

HIGH IMPULSIVITY PREDICTS THE SWITCH TO COMPULSIVE COCAINE-TAKING

Rats, like humans, can get addicted to drugs. When rats are exposed to cocaine, 15-20% of them become addicted, which is similar to that observed in humans (Belin, 2008).

“… the essential feature of addiction … [is] … the persistence of drug-seeking in the face of negative consequences …” explain researchers in a 2008 paper (Belin, 2008). In their study, they found that high impulsivity “predicts the development of addiction-like behavior in rats … [and they note that, in humans,] … there is a high comorbidity between drug addiction and disorders characterized by impulsive behavior, such as attention deficit-hyperactivity disorder.”

Low serotonin levels are thought to be a cause of impulsivity. For example, reducing serotonin levels by tryptophan-restricted diets results in more impulsive choices in experiments. A recent paper (Bevilacqua, 2010) found that a mutation in the serotonin 2B receptor predisposed a Finnish population to severe impulsivity.

Lithium may reduce impulsivity, but studies reporting this association have involved doses much higher than the low-dose form that we use. One such study (in rats) found that a “moderate” dose of lithium (20 mg/kg) suppressed impulsive behavior (Ohmura, 2012). Research involving the low concentrations of lithium found in mineral waters and in some tap water has reported reduced impulsiveness and suicide in people.

Another way to reduce impulsivity is to take tryptophan (precursor to serotonin). See above in “Eating: Delay Discounting.”
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.

Slowing Up the Aging Process in a Fast-Paced World

In today’s fast-paced lifestyles, most men are faced with increasing mental and physical Greg Royals 1985demands as they age. Personally, I have found that an easy, logical way to slow up my aging process is to keep my body and brain more fit through the use of a few essential supplements with each meal.

I urge all men to consider, at least, the use of the following supplements: a high-quality multi to insure immune support, a potent omega-3 supplement for heart and brain health, specific nutrients that help promote a healthy prostate, and a simple amino sugar (glucosamine) for cartilage health.

I feel that the consistent, daily use of the right nutrients in supplement form (and in adequate amounts!) is one of the most important health decisions that we can make. Based on the past 20 years of being in the dietary supplement industry through my company, Life Priority, and my 16 year career as a pro athlete, I feel strongly that using high-quality supplements is imperative. No matter what you have read or what your doctor, chiropractor, nutritionist, etc. might suggest, your diet is most likely lacking in one or more essential nutrients. You can help yourself feel better and slow up your personal aging process by using high-quality supplements.

I have been involved as a retail customer or a marketer of dietary supplements since 1991. Prior to ’91, I was not aware of the value or importance of getting certain nutrients in my body on a consistent basis. Don’t leave your physical and mental well-being up to anyone else! It’s your life! Your body, including your brain, is aging each day and you can give yourself a better chance at living a healthier (and happier!) life by simply using enough of the right nutrients each day with meals or at bedtime.

Life Priority, Inc., was formed in 1994 to provide customers with time-tested high quality, research-based, scientifically-formulated health and nutritional products. A major life-extension-bookreason that Life Priority was formed was because of the research of 2 scientists who were the co-authors of a NY Times best-seller Life Extension, A Practical Scientific Approach, which was written specifically for doctors. The authors, Durk Pearson and Sandy Shaw, wrote Life Extension do that doctors could understand how using certain nutrients in adequate amounts could slow up the aging process.

Durk and Sandy’s multi-vitamin/mineral formula, One Per Meal Lifeguard, contains 25 different nutrients. Each Lifeguard capsule, meant to be used after meals 3 times per day, contains more than the minimum RDA’s. Three other Life Priority products, Omega-3 Priority, Prostate Priority, and Joint Decision/Total Joint Complex provide specific nutrients not contained in the Lifeguard product but do not contain many essential nutrients for specific areas of the body.

Take the advice of someone who, in 1991 at the age of 42, was enlightened by experts in the dietary supplement industry regarding the aging process–get more essential nutrients in your body each day by using “nutrition that you can feel!”

To Your Health!

Greg Pryor-Life Priority Co-Owner and Customer

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.

LIVE LONGER WITH VITAMIN D3

The Durk Pearson & Sandy Shaw®life-extension-book
Life Extension NewsTM
Volume 20 No. 1 • February 2017

LIVE LONGER WITH VITAMIN D3
or
LIVE LESS LONG WITH LESS VITAMIN D3

Vitamin D deficiency has been linked to many chronic disorders, such as multiple sclerosis, inflammatory bowel disease, infections, immune deficiency, cardiovascular disease, hypertension, heart failure, sudden cardiac death, cancer, and Alzheimer’s disease (Gruber, 2015). But, even more than that, low vitamin D levels in serum are associated with increased mortality. In fact, in a recent meta-analysis of 42 randomized trials, taking vitamin D for three years or longer resulted in a significant 6% reduction in all-cause mortality.

In another meta-analysis (this one included 73 observational studies and 22 randomized controlled trials with 849,412 and 30,716 participants respectively), the observational studies were reported to show that “[e]ach decline of 25(OH)D [vitamin D] by 10 ng/mL was associated with a 16% increased risk of all-cause mortality (Gruber, 2015).”

Importantly, however, different forms of Vitamin D have different effects. In the randomized clinical trials noted in the paragraph above, “where vitamin D2 (dose range: 208-4500 IU/day) or vitamin D3 (dose range: 10-6000 IU/day) were given alone vs placebo or no treatment, vitamin D3 significantly reduced the mortality by 11%, whereas vitamin D2 increase[d] the mortality by 4%.” (The increased mortality seen with vitamin D2 was, however, seen with lower doses (<600 IU/day) and shorter average periods of supplementation (less than 1.5 years).) Vitamin D3 is the form of vitamin D that the two of us take.

A third meta-analysis that included 32 studies from January 1966 to January 2013 with more than 500,000 people (about 55 years old), found that serum 25(OH)D levels less than or equal to 30 ng/mL were associated with greater all-cause mortality, as compared to levels over 30 ng/mL. The authors of this meta-analysis also noted that the cutoff point for a deficient intake of vitamin D (20 ng/mL), as recommended by the federal government’s Institute of Medicine was too low to get all the health benefits of vitamin D (e.g., reduced risk of all-cause mortality and diseases such as cancer, autoimmune diseases, etc.). They suggested that the cutoff point should “not be set at 20 ng/mL, but at 30 ng/mL (Gruber, 2015).”

It is notable that the “Institute of Medicine recommended a daily tolerable upper intake (UL) for vitamin D for persons of nine years and older of 4000 IU and the Endocrine Society recommended for adults an UL of 10,000 IU vitamin D (Gruber, 2015).” We take 16,000 IU/day to attain a minimum-mortality sweet spot value of 60 ng/ml. NOTE: Do not take more than 10,000 IU/day unless you also have a blood test to verify that you are not taking too much.

It is also interesting to know that “obese individuals needed 2.5 times more vitamin D to raise the blood levels of 25(OH)D to the same degree as a normal weight person (Gruber, 2015).”

In conclusion, vitamin D3 is an inexpensive way to obtain a variety of potentially important health benefits, including the possibility of living longer.

Reference

Gruber et al. Live longer with vitamin D? Nutrients. 7:1871-80 (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.

Magnesium Reduces All-Cause Mortality, Including Stroke, Heart Failure, And Diabetes-

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 20 No. 2 • March 2017

MAGNESIUM REDUCES ALL-CAUSE MORTALITY, INCLUDING STROKE, HEARTlife-extension-book FAILURE, AND DIABETES

A very recent paper (Fang, 2016) examined the association between dietary magnesium and health. In this dose-response meta-analysis from 40 prospective cohort studies that included over one million (1,000,000) participants, the researchers found that, for each 100 mg/day increase in magnesium intake, the risk of stroke decreased by 7% (RR (relative risk):0.93; 95% CI (confidence interval):0.89-0.97, and was associated with a 10% lower risk of mortality. The highest category of magnesium intake, as compared to the lowest category, was found in the participants to reduce the risk of type 2 diabetes (RR: 0.74 (95% CI: 0.69-0.80).

“A dose-response analysis revealed that a 100 mg/day increase in dietary magnesium intake is significantly associated with a 7%, 22%, 19%, and 10% decrease in the risk of stroke, heart failure, type 2 diabetes, and all-cause mortality.” However, there was no clear association between magnesium and the risk of cardiovascular disease. In the U.S. and in Europe, the daily intake of magnesium does not generally meet the recommended amount. Epidemiological studies indicate that low levels of serum magnesium are associated with diseases such as chronic obstructive pulmonary disease (COPD), type 2 diabetes, and Alzheimer’s disease, among others (Fang, 2016).

We highly recommend taking supplemental magnesium. We take 400-600 mg per day of magnesium from our Magnesium Priority.™

Reference

Fang et al. Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. BMC Med. 14:210 (2016)

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.

*Any testimonials on this web site are based on individual results and do not constitute a guarantee that you will achieve the same results.

Your Mind is in your Hands

Your Mind Is in Your Hands

Set the stage for pursuing your personal happiness. Each new day presents challenges that, if not met and overcome, may leave you less mentally fit to control your life.

Now there’s a way to insure against the consequences of falling short of your goals and to offer you more control over your life.

By starting each day with a cool, refreshing glass of delicious LIFT™(or LIFT CAPS™), or Mind™, you can embrace a Mental Fitness™ program that can blow away your neural cobwebs and lift away the stressful storm clouds that may hold you back.*

Life extension scientists Durk Pearson & Sandy Shaw® have developed a family of products for their own personal use based on the idea of providing our brains with nutrient raw materials to manufacture neurotransmitters such as noradrenaline, which provides an adrenaline-like charge to neural circuits.* These BRAIN DRINKS are the core of Durk & Sandy’s personal Mental Fitness program. Each formulation contains the essential amino acid phenylalanine and the necessary enzyme cofactors vitamin B6, vitamin C, copper, and folic acid, along with natural flavors. With these BRAIN DRINKS as your daily allies, you can take charge of your life. So have a glass . . . Your mind is in your hands.

LIFT CAPS™ is the convenient, capsulated form of LIFT™.
Rita C. 2/5/2015- I’m taking the Lift Caps and – they’re amazing! It gives me so much energy, and I am on my feet, working and talking 9 hours a day. With the Lift Caps – what a difference people see! I’m just so happy to have my brain, body and mind back!

Matt 11/07/2015- LIFT is wonderful…without a doubt! It’s a regular part of my day and my performances.

Cindy  4/03/2014- I have been taking Lift Caps for over 10 years! They give me lots of energy and stop my craving for coffee, soft drinks and chocolate too! I LOVE THEM!

Ruth 9/23/2014- I like the LIFT because I think it gives me just what I need. I work 8 hours a day, sometimes more, with kids at school, and I just have to have the Lift in the morning. I don’t get as tired during the day when I drink it – it just works for me. I think I’m getting everything from it!

Tony 5/6/2015- LIFT helps me in the morning. I used to drink energy drinks, but this is healthier and does the same job.

Char 05/23/2014- I’ve been using Lift and Lift Caps for over 21  years and I find Lift  is the only thing that will give me the energy to go on when I feel like dropping. Love You Durk and Sandy! Thanks for your research! Please write another book!

 

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The information provided on this site is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information on this site for diagnosis or treatment of any health problem or for prescription of any medication or other treatment.

You should consult with a healthcare professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. You should not stop taking any medication without first consulting your physician.