Gregg,

I am well aware of the large amount of evidence in favor of the hypothesis
regarding phytochemicals. Still it is a hypothesis. And an interesting one.
But I advice any of you not take it for granted that they are the reason
that fruit and vegetables are healthy. I say this because many people are
too eager to make pills out of nutrients.

And just to make you realize that even extremely solid hypotheses may prove
false -- The other week we got strong evidence that there is no net
beneficial effect of estrogen plus progestin taken as pills by women with
coronary heart disease. Virtually everyone (including myself) was stunned
by the results of this well performed clinical trial:

Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E.
Randomized trial of estrogen plus progestin for secondary prevention of
coronary heart disease in postmenopausal women. Heart and
Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998 Aug
19;280(7):605-613

CONTEXT: Observational studies have found lower rates of coronary heart
disease (CHD) in postmenopausal women who take estrogen than in women who
do not, but this potential benefit has not been confirmed in clinical
trials.
OBJECTIVE: To determine if estrogen plus progestin therapy alters the risk
for CHD events in postmenopausal women with established coronary disease.
DESIGN: Randomized, blinded, placebo-controlled secondary prevention trial.
SETTING: Outpatient and community settings at 20 US clinical centers.
PARTICIPANTS: A total of 2763 women with coronary disease, younger than 80
years, and postmenopausal with an intact uterus. Mean age was 66.7 years.
INTERVENTION: Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of
medroxyprogesterone acetate in 1 tablet daily (n = 1380) or a placebo of
identical appearance (n = 1383). Follow-up averaged 4.1 years; 82% of those
assigned to hormone treatment were taking it at the end of 1 year, and 75%
at the end of 3 years.
MAIN OUTCOME MEASURES: The primary outcome was the occurrence of nonfatal
myocardial infarction (MI) or CHD death. Secondary cardiovascular outcomes
included coronary revascularization, unstable angina, congestive heart
failure, resuscitated cardiac arrest, stroke or transient ischemic attack,
and peripheral arterial disease. All-cause mortality was also considered.
RESULTS: Overall, there were no significant differences between groups in
the primary outcome or in any of the secondary cardiovascular outcomes: 172
women in the hormone group and 176 women in the placebo group had MI or CHD
death (relative hazard [RH], 0.99; 95% confidence interval [CI],
0.80-1.22). The lack of an overall effect occurred despite a net 11% lower
low-density lipoprotein cholesterol level and 10% higher high-density
lipoprotein cholesterol level in the hormone group compared with the
placebo group (each P<.001). Within the overall null effect, there was a
statistically significant time trend, with more CHD events in the hormone
group than in the placebo group in year 1 and fewer in years 4 and 5. More
women in the hormone group than in the placebo group experienced venous
thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58) and
gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were no
significant differences in several other end points for which power was
limited, including fracture, cancer, and total mortality (131 vs 123
deaths; RH, 1.08; 95% CI, 0.84-1.38).
CONCLUSIONS: During an average follow-up of 4.1 years, treatment with oral
conjugated equine estrogen plus medroxyprogesterone acetate did not reduce
the overall rate of CHD events in postmenopausal women with established
coronary disease. The treatment did increase the rate of thromboembolic
events and gallbladder disease. Based on the finding of no overall
cardiovascular benefit and a pattern of early increase in risk of CHD
events, we do not recommend starting this treatment for the purpose of
secondary prevention of CHD. However, given the favorable pattern of CHD
events after several years of therapy, it could be appropriate for women
already receiving this treatment to continue.