Cure Deficiencies First (Matt Kaeberlein & Bruce Ames)

After listening to the latest talk from Dr. Kaeberlein and reading the works of Bruce Ames (95 yo Biochemistry Professor UC Berkeley), the one thing that stuck out was that he said to cure your deficiencies first for healthspan and longevity. After that, exercise, sleep, diet, and socialization are important. Finally supplements.

So, I thought we should create a thread to list things that most/many people are deficient in and ways to treat it as this is the first step towards longer lifespan\healthspan and we often overlook it. I’m going to start off with the two biggest deficiencies I know of:

1. Omega-3s - 70% of American adults and 95% of children do not get enough Omega-3s.

Low EPA and DHA levels in red blood cells were found to be associated with increased all-cause mortality in a study of 6,501 elderly women followed for 14.9 y (32). A metaanalysis reported that each 1% increase in plasma DHA/EPA was linked with a 20% decreased risk in all-cause mortality (33).

Low blood levels of DHA/EPA were shown in a 5-y study to be associated with a faster rate of telomere shortening, a marker of cell aging (36). Supplemental fish oil (2.5 g/d) slowed telomere shortening and lowered biomarkers of oxidation in older adults (37). Daily supplemental DHA (2 g/d) increased the rate of clearance of amyloid plaques in people with mild cognitive impairment (38). DHA/EPA are important for vitamin D steroid hormone effectiveness (13). Evidence of their role in reducing the risk of heart disease has been obtained (39, 40).

Solution: 1 - 2 g of Omega 3 supplementation (2X EPA vs DHA) - or eat a lot of fish/fish oil.

2. Vitamin D3 - 70% of Americans are deficient as are 50% of American children

Vitamin D levels are inadequate in 70% of the United States population. Almost all dark-skinned people residing in northern latitudes are particularly deficient (12, 13).

Extensive evidence shows that vitamin D deficiency causes—or has been associated with—a large number of diseases that affect healthy aging, such as all-cause mortality, cancer, cardiovascular disease (CVD), diabetes, brain function, and so forth. Considering this high level of deficiency and the important implications of vitamin D interactions, it is particularly important to tune up metabolism (15) with respect to vitamin D. See SI Appendix, SI-3 Survival V/M That Are also Longevity V/M for the large literature on vitamin D clinical trials and Mendelian randomization studies.

Here you see the Hazard Ratio for low D3. You need at least 30 Serum ng/ml, but preferably 40.


Solution: 1,000 - 10,000 ius of Vitamin D3 supplementation (25 mcg - 250 mcg). I took 5,000 IUs daily, but was still deficient. I now take 10,000 ius. You also need to take Magnesium to absorb D3 and vitamin K2 also helps. I take 2 g of Magnesium Citrate daily and a MK7 K2 supplement on Mon-Wed-Fri as K2 has a long half-life.

Note: Alzheimers and Dementia patients as well as those at risk of both should avoid supplementing with vitamin D.

3. Magnesium - 45% of Americans are deficient

Mg is present in the center of the chlorophyll molecule, with plants being a major dietary source, together with whole grains, nuts, and seeds (41). Mg deficiency affects about 45% of the United States population and has been associated with increased all-cause mortality, poor DNA repair capacity, increased risk of lung cancer and various other kinds of cancer, heart disease, telomere shortening, and risk of stroke (SI Appendix, SI-3 Survival V/M That Are also Longevity V/M).

A recent review on the subclinical effects of Mg deficiency makes the case that this deficiency is a principal driver of CVD, a worldwide underrecognized problem, and thus that it is a major public health crisis (42). Mg is required to convert vitamin D to its active steroid hormone form (43).

These are just 3 of the most common deficiencies. Can anyone add any that affect 40% or more of the population?

It should be easy as the typical American diet is really deficient in so many areas. :stuck_out_tongue:


Deficiencies in Vitamins and Minerals

Approximately 30 V/M are cofactors necessary for metabolism to function properly and were discovered because severe dietary deficiencies were linked to serious adverse health effects. They include vitamins A, B1, B2, B6, B12, biotin, C, choline, D, E, folic acid, K, niacin, pantothenate; and minerals/elements calcium, chloride, chromium, cobalt, copper, iodine, iron, manganese, magnesium, molybdenum, phosphorus, potassium, selenium, sodium, sulfur, and zinc. Some additional important nutrients, the marine omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentanoic acid (EPA), are discussed here, although they are not known as vitamins. Nine essential dietary amino acids are also important for the synthesis of proteins and hormones (2) but will not be discussed. The abbreviated term V/M is used throughout this presentation because it refers to a coherent category of nutrients, although only a few minerals/elements are discussed.

Most of the world’s population—even in developed countries—consume many of the V/M at levels below those recommended (3, 4). Using as reference the estimated average requirement (EAR) values [the intake level for a nutrient at which the needs of half of the healthy population is adequate and half is inadequate (5, 6)], the following numbers are given as examples of the high percentages of the United States population ingesting V/M quantities below the EAR (including fortifications and supplements): vitamin D, 70%; vitamin E, 60%; magnesium, 45%; calcium, 38%; vitamin K, 35%; vitamin A, 34%; vitamin C, 25%; zinc, 8%; vitamin B6, 8%; folate, 8% (7). Intakes of the marine omega-3 fatty acids DHA and EPA are also remarkably low in the United States population; an EAR has not been set (8). A varied and balanced diet could provide enough V/M for a healthier and longer life. A diet containing much of its calories as refined foods and sugar is deficient in V/M and leads to an unhealthy and shorter life.

The association or causality between various diseases of aging and a number of V/M deficiencies is analyzed here by screening the literature and using as criteria clinical trials, epidemiology, Mendelian randomization studies, and biochemical and medical literature. A sampling of the literature covering the link of various diseases with V/M deficiencies is provided in SI Appendix, SI-1 Vitamin and Mineral Deficiences.


Amino Acid Deficiencies

Taurine - When we are young (late teenagers) we have a taurine level of 100-300.
When we hit age 60, we have a serum taurine level of 50-80. That’s a drop of 50% or more. This also happens for mice and monkeys (and probably all mammals). See picture below. It is reversible with supplementation.

Examples of several important insidious long-term pathologies that taurine would protect against are: CVD, brain dysfunction, and diabetes. Taurine effects on CVD have been examined by numerous RCTs and have been reviewed previously (51). Taurine supplementation lowers blood pressure, improves vascular function, and raises plasma hydrogen sulfide levels as shown in a recent RCT with prehypertension patients (58). Taurine consumption was the most significant factor associated with reduced risk of ischemic heart disease (IHD) in two international epidemiological studies of CVD in 61 populations (25 countries; n = 14,000): Japanese people in Okinawa had the highest taurine dietary intake and the lowest incidence of IHD and longest lifespan. In contrast, Japanese immigrants in Brazil who eat little seafood, but more meat and salt, had a 17-y shorter lifespan as a consequence of a very high IHD mortality (59). Other human clinical studies showed that taurine decreases platelet aggregation, serum cholesterol levels, LDL/triglyceride levels, and enhances cardiac function (60).

Guide to Taurine and Dosing:

Glutathione (GSH) - Starting at age 30, Glutathione levels start to decrease (see image below). This causes oxidative stress levels to marginally increase until age 50 at which point oxidative stress takes off as GSH production drops below maintenance levels. Glutathione production is limited by two amino acids - Glycine and Cysteine (NAC).



ITP Mouse Survival Curves

Glycine is abundant in collagen, a building block for glutathione, a precursor to creatine, and an acceptor for the enzyme glycine N-methyltransferase (GNMT). A review of the literature strongly implicates GNMT, which clears methionine from the body by taking a methyl group from S-adenosyl-L-methionine and methylating glycine to form sarcosine.

Cysteine (NAC)

Circulating GSH levels

GSH target = 1000

See: Glutathione Primer

Note how the placebo has low levels of GSH as well as 4.8 g GLYNAC under high oxidative stress conditions, but 7.2 g GLYNAC has high GSH even under high oxidative stress. Also note that under low oxidative stress, both 4.8 and 7.2 g produce enough GSH.

What this tells us, is that if we enter a high oxidative stress state, our GSH cannot cope and we start to damage our bodies.

It does appear that NAC and glutathione do affect rapamycin-induced autophagy. Therefore I will skip NAC on the day of my Rapamycin dose and the day afterward. NAC has a half-life of 6.25 hours, so a dose of 3.2 g should be cleared within a day.

Glycine and NAC have a positive correlation to improved cognitive function. The Blue (Y) group is young mice. The Red (OC) and Green (OG) are old mice. OC is control. OG is old mice receiving GLYNAC. As you can see, GLYNAC reduced errors and helped mice navigate the maze almost as well as a young mouse!


Love the idea if this thread. I’m convinced by the logic. I have a few candidates that sporadically supplement depending on diet. Usually I eat enough eggs, nuts and pulses to cover these. But these 3 in particular are reasonably difficult to cover with diet alone (espec choline)

“Mean choline intakes for older children, men, women, and pregnant women are far below the adequate intake level established”

“An estimated 17.3% of the global population is at risk of inadequate zinc intake. The regional estimated prevalence of inadequate zinc intake ranged from 7.5% in high-income regions to 30% in South Asia”

Estimating the Global Prevalence of Zinc Deficiency: Results Based on Zinc Availability in National Food Supplies and the Prevalence of Stunting - PMC.

Folate (not in folic acid form)
“MTHFR gene polymorphisms are common worldwide, with an estimated 25 percent of Hispanics and 10 to 15 percent of North American whites having the 677C>T polymorphism in both copies of the genes.”


Matt’s newest podcast that addresses deficiencies in 3 key nutrients - D3, B12 and Omega-3.


I think one key thing that Matt mentioned, but this thread has not yet put emphasis on is the value of testing and then individualizing supplement schedules and dosages based on the feedback of the testing.

2g fish oil might be good on average but some people might need any based on diet and someone else based on genetics and eg taking Ezetimibe might need twice that amount. And so on.


This is a great video by Rimon that talks all about Taurine and Taurine deficiency.


There’s no evidence that ezetimibe impacts DHA or EPA absorption.

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I just listened to Ames on another podcast. Ames’s triage theory is a great mental model for thinking about how the body adapts to its environment. Ames says your body will steal from your longevity to allow you to survive in the short run. The damage done while not providing substrate to the longevity processes are hard to fix later (and so reduce your longevity potential). This seems to be the same with nutrients needed for enzyme activity as well as calories for energy and protein for building…a shortage leads the body to steal from lower priority processes at the cellular and organ level.


Now the question is - “What other deficiencies are we missing that we need to address for optimal longevity?”

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These two are a bit complex I think as having either or both of them low actually triggers the body to rev up longevity machinery like autophagy, stress tolerance, mTOR, IGF-1, etc pathways?

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The simple idea is eating a “healthy” diet would supply the calories and nutrients needed. So what’s healthy mean? And what about diets that are constructed to accomplish other goals: reduce hunger, minimize IGF-1, not kill living things, etc.?

For simplicity I lean toward minimizing chemical interventions in favor of real and diverse food, regular and diverse exercise, regular (but not too much) sunshine, mediation, laughter, protecting my sleep, learning interesting things, meeting interesting people …. and taking a few pills (the fewer the better).

I think I’ll run away from this topic now.


Chronic shortages is the problem. Starvation is death by autophagy.


I am scheduled to get my Magnesium, B12, Omegas, and D3 tomorrow, among a few other things. I enjoy Matt’s content, and he made me think about getting these tested.


This is the best Vitamin D guide I have found.