A COCKTAIL FOR LONGEVITY & HEALTH

A VIEW FROM THE OFFICE

DIET & LONGEVITY: A NEW APPROACH

GLASSES UP! A COCKTAIL TO ROUND UP YOUR LIFE:  As you know (perhaps ad nauseam) my approach to maximizing the lifespan (i.e., reducing all-cause mortality) is to follow The Formula for Health: 0 cigarettes, 5 servings of fruits & vegetables a day, 10 minutes of relaxation a day, maintaining a BMI < 30, and getting 150 minutes of exercise each week. Now these researchers have done me one better. They offer a cocktail of 30 ingredients to delay aging and extend the life span.(1) The data are preliminary but very positive (i.e., in mice). The thesis makes perfect sense. We have learned that health is always multifactorial and never attributable to a single factor. The reason that the Okinawans live so long is that there diet has little meat but contains more than 15 different kinds of fruits and vegetables each day. These investigators have further refined the nutrition essentials to go beyond a simple one-a-day multivitamin (which, prior to this I enthusiastically supported).

        This nutrient cocktail was developed by Dr. C. David Rollo and colleagues at the McMaster University in Canada. It was not a simple ad hoc formulation, but was strategically selected to address the five key mechanisms of aging. 

THE 5 KEY MECHANISMS OF AGING

oxidative stress

inflammation

mitochondrial dysfunction

insulin resistance

loss of membrane integrity

  

"No single mechanism alone accounts for any one specific disease process. Instead, all five mechanisms interact with one another to produce both general aging and specific conditions that limit activity, cognitive function, and ultimately lifespan...All animals, from worms to insects to humans, change in very similar fashions as they succumb to the five key mechanisms of aging."  Dr. Rollo and colleagues studied the impact of these nutrients on laboratory mice because of their short normal life span." (A mouse is considered 'old' by age 2 years.) They sought to study measures that would apply equally to mice and humans. They chose to focus on how much the aging animals moved and how their cognitive function changed with time. 

        "As they grow older, all animal species move about less and less each day, spending more and more time at rest or in sleep. Reduced mobility is an excellent marker of aging, because it is closely linked to overall metabolic rate, feeding, fat storage, brain neurotransmitter levels, mitochondrial function, and cardiovascular and skeletal muscle systems...[L]loss of mobility in humans is associated with muscle wasting, bone thinning, and other changes that increase the risk of other negative outcomes such as fractures, pneumonia, and skin infections. Cognitive function also declines with age in all animal populations. Younger animals typically learn faster, requiring fewer repetitions to master a task. They can also bring up important memories faster and more accurately, allowing them to find food, escape threats, and protect other members of their species. Studies show that preserving cognitive function into older ages is associated with longer life spans."

       In the study, the 30-ingredient cocktail was soaked into small pieces of bagel. For the longevity study they used both normal mice and a special strain that demonstrates accelerated aging as a result of excessive sensitivity to all five aging mechanisms. Compared with control animals, the supplemented mice of the accelerated aging strain lived 28% longer. Supplemented normal mice survived 11% longer than controls. For the mobility component of the study the investigators placed the mice in a system of transparent chambers, where they were given food, water, and an exercise wheel; they recorded the amount of time each animal spent moving about the enclosure over a 24-hour period. "Normal, unsupplemented mice showed a progressive decline in activity; by 24 months their mobility was roughly half that of younger normal animals. By 24 months of age, supplemented normal mice were moving roughly three hours more per day than were unsupplemented animals. No other treatment has ever been found that ameliorates declining mobility to this extent."

        Dr. Rollo's group also measured biochemical markers that might explain the difference in mobility. Supplemented older mice had increased activity of the neurotransmitter dopamine (decreased dopamine levels are associated with loss of movement in aging humans and in Parkinson's disease). They also had increased measures of mitochondrial activity, "suggesting that supplemented animals simply had more energy as they aged." Finally, they measured decreased levels of protein corbonyls--altered molecules that reflect the impact of glycation and oxidation on cells and tissues.

        To assess cognitive outcomes they  tested the mice on a water maze that required the animals to find and remember the location of a platform submerged just below the surface of a pool filled with waters. This test is an indicator of both learning skills and memory. They repeated this test each day for 5 days. At first all of the animals had difficulty finding the platform taking an average of 81 seconds. By day 5 young mice had learned and remembered enough to find the platform 43% faster than on day 1. "Older unsupplemented mice, however, showed no significant improvement in the time it took them to find the platform, indicating age-related impairments in learning and memory. But with supplementation, old mice showed a level of learning almost identical to that of young mice; in fact on day 5 they took an average of 46% less time to find the platform than they did on day 1. In other words, supplemented old mice showed the same ability to learn and remember new tasks as did young animals." In the related biochemical observations they noted that brain mitochondrial activity fell steadily with age in the untreated mice, while supplemented animals showed a steady increase in this measure of brain energy supply; mice with higher brain mitochondrial activity proved to be significantly better learners than those with lower mitochondrial activity; and brain weights, which normal decrease with age, were higher in supplemented male mice by 7%, and in females by 11%, compared with brain weights of control animals.

        The editors of Life Extension Magazine (free 3 month trial subscription available at this link:  http://www.lef.org/magazine/mag2012/may2012_Nutrient-Cocktail-Delays-Aging-Extends-Life-Span_01.htm) summarize the article as follows:

1. "Aging is a complex, multifactorial process, but five major mechanisms are now known to account entirely or in part for most human age-related diseases.
2. Dr. Rollo and colleagues have developed and tested successfully in mice a 30-nutrient supplement mixture designed to attack all 5 mechanisms of aging.
3. Tested in mice, the supplement mix extends life span by up to 28% while improving the aging animals' mobility and cognitive function.
4. All 30 ingredients are known to be safe and effective in human beings.If this mixture, or one like it, has similar effectiveness in humans, one could expect an 80-year-old to add nearly 9 years of life with youthful levels of activity and cognition."

Anyone interested?

And, of course, here is the prize. The 30 ingredients of the cocktail are:

TABLE OF NUTRIENT COCKTAIL INGREDIENTS
NUTRIENT	MECHANISM OF AGING AFFECTED
	Oxidant stress	Inflammation	Mitochondrial function	Insulin resistance	membrane integrity
B vitamins (B1, B3 (niacin), B6, B12,and folate.	x		x	x
Vitamin C	x
Vitamin D		x		x
Acetyl-L-carnitine	x		x
Alpha-lipoic acid	x	x	x	x
Aspirin		x
Beta-carotene				x	x
Bioflavonoids	x	x
Chromium picolinate				x
Garlic	x	x	x	x	x
Ginger root extract	x	x	x	x	x
Ginkgo biloba	x
Ginseng	x	x	x	x	x
Green tea extract	x	x		x
L-glutathione	x
Magnesium	x			x
Manganese	x			x
Melatonin	x	x
N-acetyl cysteine	x
Potassium	x			x
Rutin	x	x
Selenium	x	x	x	x	x
Vitamin E	x
Cod liver oil (omega-3)		x			x
Coenzyme Q10	x	x	x
Flax seed oil		x			x

COMMENT:  In my opinion this list makes complete sense. Over the years in my newsletters I have reviewed favorably 28 of the 30 ingredients as having important preventive benefits; the only ones that are new to me are rutin and manganese. The table above suggests particularly potent health benefits from garlic, ginger, selenium, and ginseng. 

        One of the important trends in medicine is the evolution of the 'polypill' principal. The original 'polypill' published by Wald & Law in the British Medical Journal 2004 consisted of a recommendation for universal consumption, starting at age 50, of an aspirin, folic acid, a statin, and 3 antihypertensive agents (regardless of baseline blood pressure) in half their usual starting doses. The imputed benefits were a greater than 80% reduction in heart disease and stroke. Then came the healthy lifestyle literature starting with the Hale Study focusing on a recipe of no smoking, regular exercise, a Mediterranean diet (which contains a lot of the ingredients above), and any intake of alcohol; the reported benefits for these elderly subjects over 10 years were a 60% reduction in mortality over, a 64% reduction in coronary heart disease, a 61% reduction in cardiovascular disease, and a 60% reduction in cancer. On the lifestyle front, I further refined a healthy lifestyle to my "Formula for Health" with the imputed benefits listed below:

This article takes the evolution of this concept yet one more step farther. Expect to see much more of this in the future.

WHAT IS THE BEST WAY TO DISPOSE OF OLD MEDICATIONS?  This is an important and very practical concern. The 'experts' have previously led us to believe that to dispose of medications with minimal damage to health and the environment, they should all be dropped off somewhere (like your local pharmacy) to be incinerated. The exception to this was a previous FDA recommendation that the following medications could be flushed down the toilet:

Abstral, tablets (sublingual)	Fentanyl
Actiq, oral transmucosal lozenge *	Fentanyl Citrate
Avinza, capsules (extended release)	Morphine Sulfate
Daytrana, transdermal patch system	Methylphenidate
Demerol, tablets *	Meperidine Hydrochloride
Demerol, oral solution *	Meperidine Hydrochloride
Diastat/Diastat AcuDial, rectal gel	Diazepam
Dilaudid, tablets *	Hydromorphone Hydrochloride
Dilaudid, oral liquid *	Hydromorphone Hydrochloride
Dolophine Hydrochloride, tablets *	Methadone Hydrochloride
Duragesic, patch (extended release) *	Fentanyl
Embeda, capsules (extended release)	Morphine Sulfate; Naltrexone Hydrochloride
Exalgo, tablets (extended release)	Hydromorphone Hydrochloride
Fentora, tablets (buccal)	Fentanyl Citrate
Kadian, capsules (extended release)	Morphine Sulfate
Methadone Hydrochloride, oral solution *	Methadone Hydrochloride
Methadose, tablets *	Methadone Hydrochloride
Morphine Sulfate, tablets (immediate release) *	Morphine Sulfate
Morphine Sulfate, oral solution *	Morphine Sulfate
MS Contin, tablets (extended release) *	Morphine Sulfate
Nucynta ER, tablets (extended release)	Tapentadol
Onsolis, soluble film (buccal)	Fentanyl Citrate
Opana, tablets (immediate release)	Oxymorphone Hydrochloride
Opana ER, tablets (extended release)	Oxymorphone Hydrochloride
Oramorph SR, tablets (sustained release)	Morphine Sulfate
Oxecta, tablets (immediate release)	Oxycodone Hydrochloride
Oxycodone Hydrochloride, capsules	Oxycodone Hydrochloride
Oxycodone Hydrochloride, oral solution	Oxycodone Hydrochloride
Oxycontin, tablets (extended release) *	Oxycodone Hydrochloride
Percocet, tablets *	Acetaminophen; Oxycodone Hydrochloride
Percodan, tablets *	Aspirin; Oxycodone Hydrochloride
Xyrem, oral solution	Sodium Oxybate

        By this time, fortunately, we have the benefit of a little experience with such guidelines and thoughtful review.(2)  The problem remains that American homes are filled with unused prescription drugs. "Each year we squirrel away 200 million pounds of pharmaceuticals we don't need anymore." Flushing or trashing drugs was the traditional means of disposal for decades, but in recent years take-back programs have been encouraged. The DEA has organized four nationwide take-back events since 2010. The most recent, in late April, collected more than 500,000 pounds of unwanted medications.        Flushing has fallen out of favor for all but a handful of drugs (see above) because of concerns about water contamination. Also we have data from Sweden that participation in take-back programs tends to stagnate at around 40%. New research, however, from the University of Michigan concludes that trashing drugs may be the most environmentally-friendly option. The researchers looked at the overall environmental impact of 3 disposal methods--flushing, trashing, and incineration. They analyzed how much of the drugs would enter the environment, emissions impacts from transportation, water treatment, and burning of waste materials. Their results show that flushing allows the highest levels of drugs to enter the environment by far, and creates more pollution than trashing. Drugs collected by take-back programs are incinerated, which means that none of the medicines themselves enter the environment, but these programs produce much greater emissions of green house gases and other pollutants than either flushing or trashing. This is mostly because consumers have to travel to a drop-off point and then the collected drugs are shipped somewhere else for incineration. The investigators suggest that home disposal is beneficial because we already have an infrastructure for collecting household trash. If our take-back programs are no more efficient than the Swedish programs, then our take-back program produces three times as much pollution while allowing about the same amount of drugs ultimately to reach the environment as home disposal in the trash. COMMENT: This suggestion makes a lot of sense. While the intention of take-back programs was to spare the environment, unless you take a more global perspective, you may be doing more harm than good. I, for one, appreciate being able to put my drugs back in the trash.

REFERENCES:

1.  Life Extension Magazine. May 2012. Nutrient 'Cocktail' Delays Aging and Extends Life Span.

 This article was brought to my attention by reader Phawda Moore.

2. NPR.org/blogs/health. Trash can may be greenest option for unused drugs. accessed 9:53 am, May 18, 2012.