Ames Triage Theory of Micronutrients and Aging

Recent news about whether or not a daily multi-vitamin is worth taking, brings to mind Dr. Bruce Ames' landmark paper titled “Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage”… typically referenced as the “Ames Triage Theory of Aging.” This isn’t new. It’s been discussed, honored and validated by scientists for a number of years, but, I don’t recall it’s been reviewed here. This serves to remind us that taking a quality multivitamin daily has many benefits.

About ten years ago, PhD biochemist and molecular biologist Bruce Ames, found that cultured human cells developed DNA damage whenever a key vitamin or mineral was slightly deficient. He says, “I realized this was an overlooked area of research” and “it was this fundamental observation that led me to the Triage Theory of Micronutrients and Aging.”

The theory is that the body allocates and prioritizes (first) essential vitamins, minerals, fatty acids and amino acids to short-term survival needs such as the production of ATP and reproduction. Long-term health needs such as DNA repair are put on hold. If the body is “even moderately deficient” in one or more of the 40 essential micronutrients over a long period, mitochondrial decay and cellular damage accumulate and eventually produce age-related illnesses including cancer.

Dr. Ames explains “Triage: It’s based on a simple analogy. The term “triage” is borrowed from the field of urgent medical care. Triage means deciding which patients to treat when faced with limited resources. When presented with more patients than there are resources to treat them all at the same time, doctors must decide which patients to treat first based on the severity of their condition.” “So the patient in cardiac arrest comes first, followed by the patient with a hemorrhaging wound in need of stitches, then the patient with severe influenza, and so on. This provides the best chance for all the patients to survive.” (LEF Interview Aug 2011)

He says, “Natural selection is known to favor short-term survival at the expense of long-term survival when they are in conflict”
“I hypothesize that as the scarcity of a micronutrient increases, and after homeostatic adjustments, such as induction of transport proteins… a triage mechanism for allocating scarce micronutrients is activated that favors short-term survival at the expense of long-term health, in part through an adjustment of the binding affinity of each protein for its required micronutrient.”
(Proceedings of the National Academy of Sciences –PNAS November 21, 2006).

So what this means to us is that by ensuring an adequate supply of essential micronutrients, we can protect our DNA and mitochondria, slow down aging and ward off disease.

Dr. Ames then focused in the research lab to prove his theory.
In 2009, he and Dr. Joyce C. McCann investigated the “essentiality” of mutant mice that cannot produce a targeted protein. They discovered that five of the vitamin K-dependent proteins required for coagulation are essential and that the knockout mice died quickly, within 24-hours of birth. They also found five other vitamin K-dependent proteins that were less critical for survival and the mice survived through weaning or longer. According to the Theory, the essential coagulation proteins should access available vitamin K before the less critical proteins. The Ames Triage Theory is often referenced in coagulation discussions and mention McCann and Ames research regarding prothrombin, an essential vitamin K protein, which is less affected by vitamin K deficiency than a less essential one – osteocalcin.

In June 2011, Ames and McCann published research showing how “modest” selenium deficiency produces cumulative damage leading to age-related disease. A paper published in The Journal of the Federation of American Societies for Experimental Biology (FASE indicated testing to see if essential selenium-dependent proteins were more immune to selenium deficiency that the less essential proteins and identifies the mechanisms whereby the body “protects” essential selenium-dependent proteins at the expense of those that are non-essential. They also found that “modest” selenium deficiency and genetic dysfunction of nonessential selenoproteins are both associated with “the same set of age-related diseases and conditions including cancer, heart disease and immune dysfunction.”

The Editor-in-Chief of the FASEB Journal, Gerald Weissman, MD, said in a press release… “This paper should settle any debate about the importance of taking a good, complete multivitamin every day.”

Dr. Ames says, “The Triage Theory should help to put micronutrition on a firm foundation and lead to a more prevention-oriented medicine for age-related diseases.”

The micronutrients associated with the Triage Theory include:
acetyl-L-carnitine
alpha lipoic acid
biotin
calcium
choline
cobalamin (B12)
copper
folate
iron
magnesium
niacin
omega-3 fatty acids
pantothenate
potassium
pyridoxine (B6)
riboflavin (B-2)
selenium
thiamine (B1)
vitamin D
vitamin K
zinc

End

My comments:
Although this list of essential nutrients does not include iodine, many of us have found supplementing with iodine is very helpful not only for thyroid function but also for the many other tissues that have a high iodine requirement. Since many of us keep our sodium intake low and are not adding iodized salt at the table, unless we are eating abundance of iodine-rich ocean vegetables and fish, it’s difficult to get enough iodine to meet total body requirements. Many of us who live in areas where the soil is iodine deficient are especially at risk. (See the many other posts on the merits of supplementing with iodine.)

Check your multi-vitamin to be sure it contains all of the micronutrients listed by Dr. Ames and consider adding iodine.

Jackie


Resources:
Smith P. Life Extension interview with Dr. Bruce Ames, August 2011:31-35
[www.lef.org]

"Dr. Bruce Ames is devoted to uncovering strategies to reverse the aging process, primarily by identifying the underlying mechanisms of degenerative disease. Best known for his groundbreaking research on the mitochondria, Dr. Ames’s lab was the first to document the synergy of lipoic acid and acetyl-L-carnitine for optimizing mitochondrial function.
Following this work, Dr. Ames recently developed the Triage Theory of Aging. His hypothesis centers on the potentially long-term damage of moderate micronutrient deficiencies, including DNA damage leading to cancer. The scope of his research also includes investigations into the mutagenic causes of cancer.

Dr. Ames has authored over 500 research papers. Currently, Dr. Ames is emeritus professor of biochemistry and molecular biology at the University of California, Berkeley and a senior scientist at Children’s Hospital Oakland Research Institute. In this exclusive interview with Life Extension Magazine®, Dr. Ames discusses some of his major areas of research."

Bruce N. Ames, PhD – CV
[www.bruceames.org]
[www.bruceames.org]

Ames, BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17589-94. Epub 2006 Nov 13.
[www.ncbi.nlm.nih.gov]
[www.ncbi.nlm.nih.gov]
Excerpt from Abstract
“Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells ar in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset disease such as cancer. I propose NNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging and neural decay but could leave critical metabolic functions, such as ATP production, intact.”

McCann JC. Ames, BN. Adaptive dysfunction of selenoprotein from the perspective of the theory: why modest selenium deficiency may increase risk of disease of aging. FASBE J. June 2011;25(6):1793-1814.
[www.fasebj.org]

---Vitamin K, an example of triage theory: is micronutrient inadequacy linked to disease of aging? Am J Clin Nurt. 2009:90:880—907

Federation of American Societies for Experimental Biology. California scientists discover how vitamins and minerals prevent age-related diseases. EurkAlert. May 11, 2011.

Townsend Letter, November 2011, $51/year [www.townsendletter.com]

Thank you, this is very interesting and important - it extends understanding about faulty protein structuring, as in cell membranes' IMPs (integral membrane proteins), seeing "channelopathies" as not necessarily caused by gene mutations.

With consideration to the “triage” theory that suggests the body prioritizes the use of scarce micronutrients in favor of short-term survival at the expense of long-term health.....studies have shown the consequences of vitamin K restriction related to vitamin K-dependent proteins.

It was found that when the supply of vitamin K was limited, (typical American diet) the body utilizes it to provide critical metabolic functions in the liver… which unfortunately, leaves other vitamin K-dependent proteins such as for bone building, cancer prevention and protecting the heart from atherosclerosis without enough vitamin K for proper function.

This obviously leaves the body at risk for developing age-related diseases like cancer, heart disease and osteoporosis.
(The same is true for long-term warfarin use)…same K deprivation.

The research noted that vitamin K deficiency was wide spread. Even when a multivitamin is used, they contain little, if any, vitamin K.

The researchers wrote: “ A triage perspective reinforces recommendations of some experts that much of the population and warfarin/Coumadin patients may not receive sufficient vitamin K for optimal function of the vitamin K-dependent proteins that are important to maintaining long-term health.”

In other studies, researchers found that vitamin K2 but not K1, significantly reduced the risk of cardiovascular disease by 57%, death from all causes by 26% and severe aortic calcification by 54%. Vitamin K1 did not provide significant cardiovascular protection.

Vitamin K is found in leafy green vegetables such as lettuce, broccoli and spinach and makes up about 90% of the vitamin K consumed in the diet. Vitamin K2 (and remember this is the MK 7 form- menaquinone 7) is the other form and is found in meat, some cheese and natto food.

Most people do not get enough of both K1 and K2 MK7 from food sources to prevent these age-related risk factors.

Reference:
McCann JC, Ames BN, Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 2009 August 19.