This guide was written and researched by MR and adapted
for the web by CRON-WEB.
Disclaimer:
MR used to formulate supplements and earn money in the process. MR no
longer does so, but still has a relationship with the company (AOR.ca).
In addition, I (Khurram) was this company's webmaster in 2004
and 2005. There are some plugs for the company's products in this Guide,
but CRON-WEB is not affiliated with AOR in any way.
What is “life extension”?
- Not accident avoidance, hygiene
- Not correction for genetic disorders
- Not correction for poor lifestyle
- Extension of health (and therefore lifespan) beyond expectations
for a basically healthy person living a basically healthy lifestyle.
CR [calorie restriction] “has been repeatedly shown to increase life
span and delay the onset of age-associated pathologies in laboratory mice
and rats.”[1]
“For more than 60 years the only dietary manipulation known to retard
aging was caloric restriction, in which a variety of species respond to
a reduction in energy intake by demonstrating extended median and maximum
life span.”[2]
No confirmed evidence for life-extending effects of any drug
or supplement in normal, healthy mammals.
Animal Studies
- ‘Successes’ in short-lived strains, suboptimal environments (well-cared-for,
normal mice, average LS ~900 days, max ~1200).
- Failures in well-cared-for animals. Eg. “Mice were fed modified AIN76
diet or modified AIN76 supplemented with vitamin E, glutathione (GSH),
vitamin E and GSH, melatonin, or strawberry extract starting at 18 months
of age [~54 human years]. … Lesion burden and incidence of specific
lesions observed amongst the various groups in this study did not differ.
There were no differences observed for longevity of any of the study
groups. The longevity observed in this study was similar to that previously
reported for male C57BL/6 mice.”[3]
- Eg. LEF LifeSpan Project: melatonin; CoQ10; lipoic
acid (racemate); aminoguanidine; lipoic acid (racemate) + aminoguanidine
+ CoQ + Pregnenalone; ALCAR + lipoic acid (racemate) + lycopene + alpha-tocopherol;
ALCAR + lipoic acid (racemate) + CoQ + NADH; melatonin + pregnenalone.
No effect (see graphs)![4]
- Deprenyl: data reviewed in ([5]).
Only Knoll (inventor has reported increased lifespan for deprenyl; variations
by strain, age, etc, in response; no reasonable basis for human dosing.
Human
Studies
Epidemiology
- Highly inconsistent; many negative findings; much weak design (case-control,
external referent population etc).
- Highly confounded. “[S]upplement use tended to increase
with age, education, physical activity, fruit intake, and dietary fiber
intake and to decrease with obesity, smoking, and dietary fat intake.”[6]
- Hidden vulnerable subpopulations. Eg folate and colon
cancer in Nurses' Health Study. Preliminary finding: “Higher … folate
intake … was related to a lower risk for colon cancer (RR, 0.69 ...
for intake > 400 microg/d compared with intake < or = 200 microg/d)
… [Among] Women who used multivitamins containing folic acid … After
15 years of use … risk was markedly lower (RR, 0.25 [CI, 0.13 to 0.51]),
… the benefit of long-term multivitamin use was present across all levels
of dietary intakes.”[7]
- But: “Compared with women without a family history who
consumed 200 µg or less of folate/day …, women without a family
history who consumed >400 µg/day experienced a multivariate RR
of 0.91 (95% CI, 0.69–1.19), … and women with a family history who
consumed >400 µg/day experienced a RR of 1.30 (95% CI, 0.82–2.08).
… Among women with a family history, the RR for those who consumed
>400 µg/day was 0.48 (95% CI, 0.28–0.83) when compared with women
with a family history who consumed 200 µg or less per day.”[8]
- Most epidemiological results demonstrate danger of deficiency, not
protective effect of megadosing (eg. folate (<200 vs >400 mg (DRI)
and colorectal cancer, fish and CHD (no additional protective effect
beyond 2 servings/week),[9] etc).
Randomized, Controlled Trials
Heart disease
- Alpha-tocopherol
- CHAOS: 400-800 IU RRR-alpha-tocopherol/d vs placebo: “a significant
reduction in the risk of non-fatal MI …; however, there was a non-significant
excess of cardiovascular deaths”.[10]
- Several other large studies report no effect on any carciovascular
outcome.[11],[12],[13],[14]
- Antioxidant “Cocktails”
- WAVE: 400 IU alpha-tocopherol + 500 mg C ± HRT vs placebo.
“Death, nonfatal MI, or stroke occurred in … 26 vitamin patients
and 18 vitamin controls (HR, 1.5; 95% CI, 0.80-2.9).”[15]
- HATS: Simvastatin ± antioxidants (800 IU alpha-tocopherol,
1000 mg C, 25 mg natural beta-carotene, 1000 mcg Se) ± placebo.
“The average stenosis progressed by 3.9 percent with placebos, 1.8
percent with antioxidants (P=0.16 … ), and 0.7 percent with simvastatin-niacin
plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin
alone (P<0.001). The frequency of the clinical end point was
24 percent with placebos; 3 percent with simvastatin-niacin alone;
21 percent in the antioxidant-therapy group; and 14 percent in the
simvastatin-niacin-plus-antioxidants group.”[16]
- Heart Protection Study: 600 mg alpha-tocopherol, 250 mg
C, and 20 mg b-c daily) vs. placebo. “[N]o significant differences
in all-cause mortality …, or in deaths due to vascular … or non-vascular
… causes. Nor … in the numbers of … non-fatal myocardial infarction
or coronary death …, non-fatal or fatal stroke …, or coronary or
non-coronary revascularisation ... For the first occurrence of any
of these “major vascular events”, there were no material differences
… There were no significant effects on cancer incidence or on hospitalisation
for any other non-vascular cause.”[17]
Cancer
- ATBC: 20 mg synthetic b-c &/or 50 mg alpha-tocopherol vs.
placebo in smokers. “No overall effect was observed for lung cancer
from alpha-tocopherol supplementation … beta-carotene supplementation
was associated with increased lung cancer risk (RR = 1.16 …). The beta-carotene
effect appeared stronger, … in participants who smoked at least 20 cigarettes
daily (RR = 1.25; …) compared with those who smoked five to 19 cigarettes
daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol
intake (> or = 11 g of ethanol/day [just under one drink per day];
RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake
(RR = 1.03; 95% CI = 0.85-1.24).”[18]
Later reports: no effect on gastric,[19]
urinary tract,[20]
colorectal,[21]
cataract,[22]
or maculopathy;[23]
no clear effect on pancreatic[24]
or colorectal[25]
cancers; 50 mg alpha-tocopherol decreased, but synthetic b-c may have
increased, clinical prostate cancer incidence and mortality.[26]
- Physicians' Health Study: 50 mg synthetic b-c EOD vs. placebo.
“Virtually no early or late differences in the overall incidence of
malignant neoplasms or cardiovascular disease, or in overall mortality
... Among current and former smokers, there were also no significant
early or late differences in any of these end points.”[27]
- CARET: 30 mg synthetic b-c and 25 000 IU of retinol in smokers,
former smokers, and workers exposed to asbestos vs. placebo. RR of lung
cancer of 1.28; RR of death from any cause 1.17; of death from lung
cancer, 1.46; and of death from cardiovascular disease, 1.26 (95 percent
confidence interval, 0.99 to 1.61).[28]
- Supplementers lost benefit of fruits and veggies![29]
- Antioxidant Polyp Prevention Study: Actually potentially positive
(!): recurrence of colon adenoma. 25 mg synthetic b-c and/or vitamins
C and ‘E’ in vs. placebos. “Among subjects who neither smoked cigarettes
nor drank alcohol, beta-carotene was associated with a marked decrease
in the risk of one or more recurrent adenomas (RR = 0.56, 95% CI = 0.35
to 0.89), but … a modest increase in the risk of recurrence among those
who smoked (RR = 1.36, 95% CI = 0.70 to 2.62) or drank (RR = 1.13, 95%
CI = 0.89 to 1.43). For participants who smoked cigarettes and also
drank more than one alcoholic drink per day, beta-carotene doubled the
risk of adenoma recurrence (RR = 2.07 … P for difference from nonsmoker/nondrinker
RR <.001).”[30]
Ambiguous evidence from CARET and ATBC on role of alcohol – more distal
sites?
- Clarke et al JAMA selenium trial: 200 micg Se/day vs. placebo
in persons with a history of skin cancer. No effect on primary end points
(incidences of basal and squamous cell skin cancer); post-hoc endpoints,
“nonsignificant reduction in all-cause mortality … [RR; 0.83; 95% CI,
0.63-1.08] and significant reductions in total cancer mortality … [RR,
0.50], total cancer incidence … [RR, 0.63], and incidences of lung,
colorectal, and prostate cancers.”[31]
- However…
- “The patient population in this trial was recruited from the eastern
coastal plain of the [US],
a region characterized by relatively low [Se] levels in soil and
crops [refs], and by high rates of [squamous cell carcinoma] and
[basal cell carcinoma] of the skin and cancer mortality.[ref]” 31
- “participants with baseline plasma selenium concentrations in
the lowest two tertiles (<121.6 ng/ml) experienced reductions
in total cancer incidence, whereas those in the highest tertile
showed an elevated incidence (HR = 1.20, 95% CI = 0.77-1.86).”[32]
- Linxian Trial: Also successful; also in an intentionally-selected
deficient population.[33]
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