CR III Conference talk summary
Summary by Dean Pommerleau


Speaker 7: Michael Rae: The Art and Science of Supplementation: Priorities, Pitfalls and Practice

Works in R&D and product development at AOR - Advanced Orthomolecular Research. Leading provider of cutting edge supplements.

Caveat: Michael's company sells supplements.

CR practitioners are all over the map wrt to supplements, some take 1/2 a centrum multi-vitamin, and others take fistfuls of supps. Neither is very wise, according to Michael.

Drive of "magic pill" isn't working out very well. Eg. CoQ10 doesn't seem to extend lifespan.

CR still only "proven" strategy. Pills have no proof.

Anything beyond CR is a gamble. The question is risk vs. potential reward.

Michael's strategy - Tier approach. Early tier is no-brainer. Further tiers more speculative.

You CAN do yourself harm with the wrong supplements, or too much of the right supplements. Low quality supplements can even have nasty toxins in them.

We don't want to shoot ourselves in the foot...

Too much reliance on test tube studies to justify supplements. Easy to kill cancer cells in a test tube. The challenge is to avoid killing the normal cells!

Too much thinking that "if is useful for correcting disease, it should also enhance normal people".

Michael's Basic No-nos - Don't take / do the following supplements:

  • Retinol > 2000 IU
  • Excess Mn (UL 11mg)
  • Synthetic Beta-Carotene
  • Excess Beta-carotene (> 15,000 IU) - no justification for taking this much
  • Excess Alpha-tocopherol? (> few scores of IU) (normal vitamin E,)
  • Substances w/ no human data
  • Graviola
  • DHA, Fish Oil ??? - good for people eating SAD, but may not be good for CRers
Looks like EPA is active ingredient for psychological disorders. People may want to consider straight EPA.

Encouraged people to read section in Walford's 120 Year Diet on "The Nature of Evidence". Great way to learn about how to treat evidence, for supplements and other scientific findings.

Now strong evidence that tomatoes, and specifically lycopene, prevents prostate cancer.

Tier system:

Tier 1: Essential Supplements

Orthomolecules only - basic vitamins and minerals
Avoid deficiency - Stuff you'll die or get really sick without in long run
Specific disease / risk factors - Niacin if you have genetically bad cholesterol

1a) Avoid frank deficiencies

  • Scurvy, beriberi, pellagra will kill you dead
  • Much cancer & heart disease from micronutrient deficiency
  • Adult-onset CR fails w/o generous micronutrient supply

Unrecognized Essentials:

  • Lithium
  • Pyrroloquinoline Quinone (PQQ) - required for lysine metabolism
  • Boron

Tier 1 Targets - here is where to look:

  • http://www.crnusa.org/about_recs.html + 1000IU of vitamin D3
  • Crunch the numbers - www.nutritiondata.com, nutribase, DWIDP
  • Common CR diet deficiencies: Mg, Zn, B1, B2, B6, Protein, impaired Metabolism of Ca, Fe, A.
  • Get ferritin test! Dean P. anemia at 242% - DRI. Mostly non-heme.
  • CR protects us against B1, Mg, Cu deficiencies - don't need as much as normals.
Biochemical Individuality: Each of us has different Genes, different life stresses
  • some people need more stuff than others - Folate, Riboflavin for certain genetic Population
  • RDA's are designed to meet nutritional needs of 95% of population
Michael's "Insurance Intuition": 1.5x RDA for minerals. Up to 10x for water-soluble vitamins (e.g vitamin C).

His recommendation - Start w/ diet, and then supplement basics to get to 1.5x RDA of minerals.

See above caveats for fat soluble.

Strong evidence for vitamin K2 for osteoporosis avoidance.

Balance is important!

  • Zn:Cu balance is important - they compete with each other.
  • B vitamins. Megadose of 1 depresses others
  • Ca vs. P, Zn, Cu, Fe

1b) "Pharmacologic" supplements for specific disease/Risk factors

If you have these risk factors, you might take these supplements:

Bone heath - Age, low DXA, very slim, dramatic weight loss - take strontium, K2
Bad cholesterol - Niacin

Tier 2 - "Good-Diet-in-a-Pill"

Dietary supplements

Small number of specific nutrients with safety & efficacy from combination of of prospective epidemiology, with independent variables, and experimental studies.

Evidence-based phytochemicals:

  • 13C - Brassica (e.g. broccoli extract, raw veggies) - 20mg
  • Sulforaphane - Brassica (e.g. broccoli extract, raw veggies) - 7mg
  • Allyl sulfides (garlic) : 55 mcg
  • Limonene (citrus): 20mg
  • Trans-resveratrol (red wine): 1.8mg = 1 glass of red wine per day
  • Chlorophyll(in) (green vegges): 300mg
  • Lycopone 18mg
  • EgCG - 1500mg
  • Flavonoids (onions, apples, tea, etc.)
  • D-Glucarate (?): 15mg
Where to find the above phytochemicals?
  • Try to get them in diet first
  • Orthocore (AOR) - Multi-vitamin + most of the above phytos
  • Trans-resveratrol - Network Synergy (AOR)
  • Limonene - BioCare Vitasorb or Pinnacle Cold Immune
Will all this stuff make a difference?

Observation that unless we're retarding aging, there is only so much more mortality curve squaring we can do. We already have a pretty darn square curve.

Showed very cool graph of human mortality data where each curve represents a different year, ranging from 10000 BC to present. Curve has successively gotten very close to square. Not much room for improvement.

If we eliminate all cancer tomorrow and you are 50 years old, you would only

Tier 3: "Sensible" "Megadose" supplementation

Dietary Supplements; Large human clinical trials showing safety
  • R+LA
  • CoQ
  • NAC (pulmonary disease)
  • Complete E complex
  • Selenium (cancer)
Selenium & Cancer - 200mcg Se cut incidence of new cancers in humans (previously skin cancer patients) by 37%, cancer deaths by 50%. But didn't help w/ skin cancer. But the people who really benefited were people who didn't metabolize selenium well. Unfortunately you can't tell with any available tests if you're one of them.

Signs of selenium toxicity - fingernail ridges and garlic breath.

Good idea to take Selenium as SeMC - much more effective at lower doses than standard selenomethionine. AOR selenium is SeMC - shameless plug...

Stuff Michael takes himself, but a bit further down in tier system:

  • Arginine - 4g/day
  • IP6
  • Methylcobalamin 0.5-5mg
  • Carnosine, 1500mg
  • Phyroglutamate - wake up your brain
  • ALCAR - alertness and memory
  • Tyrosine - like caffeine w/o addictive
  • DMAE - also a bit like caffeine also

Tier 4 - Life extension Level

NO CONCLUSIVE EVIDENCE!!!!

Things keep failing.

  • R+LA (Lipoic acid in "right" form) - not as optimistic as he used to be
    • The hope: "rejuvenation of normally-aging rats
    • Reduces mtROS production (?)
      But big caveats!
    • No mortality benefit from "wrong" standard form - Weindruck & Prolla
    • No benefit on morality for R+ form + ALCAR - Ames - unpublished
  • CoQ10 - doesn't extend mortality. Might even marginally shorten life of rodents
De Grey says the problem w/ life extension studies of supplements in rodents is that 95% of them die of cancer. If you retard aging, but not cancer, you won't see effect in mouse. Could be what is happening w/ these negative supplement studies. They may work in people, but not mice.

But w/o rodent studies, what have we got? We're up a creek w/o a paddle. Need cancer resistant mice strains to probe further.

CoQ10 - poster child for failure of initially promising supplement to extend rodent lifespan.

Stop taking CoQ10 - some evidence of "crap" in hearts, livers and kidney in mice in CoQ10 group. May be why there was a hint of *decreased* lifespan from CoQ10 in mice.

Resveratrol:

  • Looks promising
  • Trans-isomer is important - if it is going to work. Most supps in wrong form
  • No mammalian LS data - even for Sirtuin activation, say nothing of resveratrol
  • Fly study may only be curve squaring
  • Resveratrol Pharmacokinetics - some question of whether resveratrol activates
  • SIRT1 in vivo - resveratrol is heavily metabolized, rapidly cleared. May do the reverse of what we want in higher dosage. Wide variety of levels in organs. May retard aging in one organ and accelerate it in another. We don't know...
  • Questionable bioavailability.
  • Fly data exaggerated. About 1/2 the lifespan effect of CR in flies. Control flies in resveratrol studies seem unusually short lived - only corrective affect?
Michael says - Right now you're taking a risk if you take resveratrol supplements. Not justified. Benfotiamine + Pyridoxamine (PM)
  • Real anti-glycation nutrients: documented in diabetic animals and humans
  • Could therefore be beneficial - 150-300mg Benfo; 200mg PM in humans - shown To reduce glycation.
  • Seems to be "contaminant" in all available PM - could be benign, but could be hideously toxic.
Didn't have time for three case studies he'd planned. Cut and paste of highlights directly from his talk:

Case Study 1: Judy Dunn:

What she is doing:
OrthoCore       9 x
Calcium citrate        400 mg
Magnesium citrate      200 mg
B12 shot               1cc once a month
Folic Acid             5 mg
Flax oil               1 g
[Iron  10 mg]
Fish oil               1 g
EGCG                   3 x day
CoQ10                 30 mg
R(+)-Lipoic Acid       3 x
[SeMC]                     _
Benfotiamin            2 x
Carnosine              2 x
OrthoMind              3 x
MSM                    1000 mg
l-Tyrosine             500 mg
Kyolic garlic extract  600 mg

What she should do:
  Tier1:
     50% of well-designed multi
     All Bs
     E complex, Cu, Zn, Fe
    227 mg Sr; 5-15 mg menatetrenone?

Tier 2:
75% OrthoCore as basic multi
EgCG, Limonene

Tier 3:
Network Synergy
200-600 mcg Se (as SeMC)

Tier 4:
R(+)-LA: Top up to 500-600 mg, + extra biotin
Benfotiamine: 300 mg
Trans-resveratrol, when available?
Metformin (1500 mg)??

Case study #2: April Smith:

What she's doing now:
OrthoCore       9 x
Calcium citrate        400 mg
Magnesium citrate      200 mg
B12 shot               1cc once a month
Folic Acid             5 mg
Flax oil               1 g
[Iron  10 mg]
Fish oil               1 g
EGCG                   3 x day
CoQ10                 30 mg
R(+)-Lipoic Acid       3 x
[SeMC]                     _
Benfotiamin            2 x
Carnosine              2 x
OrthoMind              3 x
MSM                    1000 mg
l-Tyrosine             500 mg
Kyolic garlic extract  600 mg

Whatshe should do:

Tier 1:

50% of well-designed multi, incl. retinol
Calcium (63-80%) + D, Iron (89-149% - non-heme; woman, but ), Zinc (76-82%)
-- & Copper 146-163%
Fiber
Nearly vegetarian: taurine (250 mg), creatine (5 g), carnitine (ALCAR pref)
(500 mg), carnosine (500 mg), choline (200-500 mg).
227 mg Sr; 5-15 mg menatetrenone

Tier 2

50% OrthoCore as basic multi
EgCG, Limonene

Tier 3
Network Synergy
200-600 mcg Se (as SeMC)

Tier 4:
R(+)-LA: Top up to 500-600 mg, + extra biotin
Benfotiamine: 300 mg
Trans-resveratrol, when available?
Metformin (1500 mg)??

Case study #3: Dean Pomerleau

What he's doing now:

OrthoCore       9 x
Ortho-Bone      5 x
L-Methionine (LIVD)     500mg
Flax seed oil 3x1g gelcaps                                        Iron
Niferex 150 - Prescription      150mg (elem)
DHA     400mg/wk

Strontium 227mg
Carnosine (LIVD) 500mg
ALCAR (Lower Lp(a) + LIVD)      500mg
R+ Lipoic Acid (balance ALCAR) 300mg

Tier 1:
50% of well-designed multi, incl. retinol
Iron (history of anemia)
Small dose of flax oil (Omega-3 (g) 3.14; Omega-6 (g) 7.28. Shorts (vegan)).
Vegan: taurine (250 mg), creatine (5 g), carnitine (ALCAR pref) (500 mg),
carnosine (500 mg), choline (500 mg).
ALCAR (1500 mg total): Lp(a), in which case 600 mg R(+)-LA
Niacin (2000-4000 mg, niacin or inositol hexanicotinate) if Lp(a) doesn't
normalize.
227-545 mg Sr; 15 mg menatetrenone (weight loss; known low DEXA; Fosamax
use).
Low-dose Ca before sleep

Tier 2

50% OrthoCore as basic multi (+ extra choline)
EgCG .?

Tier 3
Network Synergy
200-600 mcg Se (as SeMC)

Tier 4:
R(+)-LA: Top up to 500-600 mg, + extra biotin
Benfotiamine: 300 mg
Trans-resveratrol, when available?
Metformin (1500 mg)??

Michael's Bottom line, take home message:

  • Don't be malnourished
  • Don't count on pills -- and don't kill yourself with them!
  • Cut your Calories -- but understand it to be unproven, weak, crude medicine.
  • Participate in CR List; support CRS
  • Support Methuselah Foundation www.methuselahfoundation.org.