by Bryan Haycock - First came Ipriflavone, sold as an anabolic
isoflavone. It was preceded by hype and mystery, both tantalizing and
frustrating to anybody "in the know" and not on drugs. A lot of people
bought it, including me. A lot of people stopped buying it a short time
after. A short time after they didn't notice any new muscle growth, that
is. Then came 5-methyl-7-methoxy-isoflavone, a slightly tweaked version
of Ipriflavone. It was also preceded by a lot of hype and mystery. As
you might expect, a lot of people bought it (not me). It appears people
are still buying it.
I have always been one to do my homework on any new supplement I was
interested in trying. Not that I'm more savvy than other people, it's
just that I've always had a fairly limited supplement budget and
couldn't afford to waste my money. When doing your homework on
supplements, you have to ask yourself a couple of questions. First, what
is being claimed about a particular supplement? Second, do the claims
make sense given the mechanism of action? In trying to answer these two
questions you will be lead to the right information to help you make
savvy supplement purchases.
So what about Ipriflavone and/or 5-methyl-7-methoxy-isoflavone? What
are the claims? What is the mechanism of action?
The claims made by those selling the stuff are as follows:
"the ultimate, "perfect" anabolic agent. You may be saying to
yourself, "I've heard this story before." Well, you may have, but
this time the story has a different ending ? it's true!"
"It [5-methyl-7-methoxy-isoflavone] was originally
designed to increase lean mass on animals and humans, without the
negatives associated with steroids."
"it's [5-methyl-7-methoxy-isoflavone] not only
anabolic, it's healthy!"
"it [5-methyl-7-methoxy-isoflavone] significantly
increases calcium, phosphorous, potassium, and nitrogen retention,
which clearly shows its anabolic horsepower."
"so powerful it's guaranteed to help you pack on up to 10
pounds of rock-hard mass in just 30 days!"
"it [5-methyl-7-methoxy-isoflavone] works."
"?5-methyl-7-methoxy isoflavone (methoxivone), the strongest
Nutrient partitioning isoflavone. Potent for gaining muscle, losing
fat, and increasing vitality, well-being and endurance. Also useful
in suppor[t]ing strong, healthy bones, and maintaining low
I could go on and on, but I'll spare you. The point I'm trying to
make is that the people making and selling this stuff are telling us it
is the "perfect anabolic." That's a pretty hefty claim!
Our second step in determining the value of ipriflavone/methoxyflavone
is to figure out the mechanism of action. The mechanism of action refers
to what and how it changes the chemistry of the body. Let's review the
relevant research. Keep in mind that ipriflavone and
5-methyl-7-methoxy-isoflavone (methoxyflavone) are assumed to have the
same mechanism of action, so I will use Ipriflavone and methoxyflavone
Ipriflavone inhibits bone resorption:
Most people familiar with Ipriflavone know that it has been
extensively studied with respect to bone metabolism, or more
specifically, osteoporosis. For instance, one representative animal
study found ipriflavone inhibited parathyroid hormone-, vitamin D-,
PGE2-, and interleukin 1߭stimulated bone resorption (1). The effects of
Ipriflavone on bone loss have also been demonstrated in humans. The same
protocol was used throughout most of these studies (i.e. 200 mg
ipriflavone or placebo three times daily). Several two-year studies
looked at women immediately postmenopause (age 50-65) and found bone
mass was maintained or improved slightly in the ipriflavone groups while
those in the placebo groups experienced significant bone loss (2,3,4,5).
This research on bone metabolism doesn't really back up "the perfect
anabolic" claims made by the supplement companies. There still may be
hope however, as other research has been done looking at slightly
different physiological effects.
Ipriflavone acts as an estrogen "sensitizer" in several tissues:
Before you shriek at the thought of enhancing estrogen's effects,
read on to see exactly how this happens. While Ipriflavone does not have
any significant direct estrogenic effects, it does enhance the effects
of estrogen, particularly in bone, the thyroid gland, and the
gastrointestinal tract (6,7). In bone, ipriflavone makes estrogen's bone
sparing effect more potent. Ipriflavone, like the soy flavone genistein,
has decent affinity for the estrogen receptor-beta (8).
OK, so this still doesn't exactly sound like the "perfect anabolic."
Ipriflavone and methoxy do have other effects.
Ipriflavone's effects on Ca2+:
In the heart, ipriflavone has been shown to prevent Ca2+ ions from
building up in the mitochondria (9). Ca2+ builds up in mitochondria when
there is insufficient oxygen. Ipriflavone actually enables heart muscle
tissue to survive longer without oxygen. This means less damage due to
hypoxia (lack of oxygen). No studies have been performed looking at
skeletal muscle function during ipriflavone supplementation however, it
is not unreasonable to assume a similar function in skeletal muscle.
More research is needed in this area.
OK, I will let you in on a little secret. All of the claims about the
"anabolic" properties of ipriflavone and methoxyflavone are based on the
claims made in their respective patents. Here is an excerpt from one of
the patents on Ipriflavone United States patent number 3,949,085.
"Test of anabolic effect: The investigation was carried out with
castrated rats by means of the musculus levator ani test and
vesicula seminalis test. The preparations were administered orally
for a period of three weeks. The tests were performed by the method
of Eisenberg and Gordan (Eisenberg, E., Gordan, G. S. J.: J.
Pharmacol. 99, 38, 1950). In addition to that, also the weight of
the prepared diaphragm of the animals was established. According to
these tests, the weight of musculus levator ani rose by a Student
significance of p 0.01, the weight of vesicula seminalis did not
increase while the weight of the prepared diaphragm of the animals
increased by a Student significance of p 0.05. On the basis of these
results the preparations proved to possess the anabolic activity
free from androgen effect."
The patent goes on to relate?
"The weight yield increasing effect induced by doses of 2 g/100
kg of feed was in the various animal species as follows:
8 to 15% in calves
7 to 10% in cattle
7 to 10% in hogs
8 to 20% in poultry
10 to 20% in rabbits
8 to 12% in guinea pigs"
The amount of feed given to these animals did not increase, only
their body weights increased. They did test their new compound on ill
humans as well:
"The anabolic effect of the composition was tested on thinned (asthenic),
reconvalescent, dystrophic patients suffering from pathological
thinness. It has been found that as a result of a treatment lasting
for some weeks the patients have gained 2-3 kg of weight. According
to our experiments the physical condition of the patients has also
In the patent on 5-methyl-7-methoxy-isoflavone (U.S. patent
4,163,746), the details on increasing ipriflavone's effectiveness are
outlined. Several compounds are mentioned, namely
5-methyl-7-isopropoxy-isoflavone. The same guys filed the
5-methyl-7-methoxy-isoflavone patent some 3 years after they filed the
ipriflavone patent. Basically, all this patent does is show that when
you methylate the isoflavone, you make it nearly twice as anabolic
compared to ipriflavone. The claims are the same except that I noticed
the claim that the "compounds are useful as anorexigenic agents. A
significant advantage of these compounds over known catabolic agents is
that they do not exhibit a central stimulating effect." Now this is
quite a claim to add to the fact that they profess that it is an
anabolic, as well. So not only does it cause a shift towards more
muscle, it also decreases appetite at the same time. Thus far, no
manufacturers that I have seen make the claim that ipriflavone or
5-mthyl-7-methoxy-isoflavone is a good appetite suppressants. But if
they wanted to I guess they could, based on this patent.
One note about patents; just because an individual or company gets a
patent, does not mean that their claims are accurate about their
invention. It only means that whoever was assigned their file at the US
patent and trademark office approved their file for a patent. It would
certainly be nice to see someone do a little research on these flavones
to see if in fact there are measurable anabolic effects when given to
humans at reasonable doses.
Still, I do feel that ipriflavone/methoxyflavone is a valuable
supplement to anybody who trains regularly. It "should" help to
strengthen bones and tendons and even enhance cellular metabolism. If
the patents are true, it may even increase muscle mass and decrease fat
mass if used long enough. Keep in mind that we only answered the first
question completely. There is still NO good explanation of how
ipriflavone or its methylated derivatives could produce non-hormonal, or
hormonal for that matter, anabolic effects.
1. Tsutsumi N, Kawashima K, Nagata H, et al. Effects of KCA-098 on
bone metabolism: comparison with those of ipriflavone. Jpn J Pharmacol
2. Adami S, Bufalino L, Cervetti R, et al. Ipriflavone prevents
radial bone loss in postmenopausal women with low bone mass over 2
years. Osteoporos Int 1997;7:119-125.
3. Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment
with ipriflavone in postmenopausal women with low bone mass. Calcif
Tissue Int 1997;61:S19-S22.
4. Agnusdei D, Crepaldi G, Isaia G, et al. A double blind,
placebo-controlled trial of ipriflavone for prevention of postmenopausal
spinal bone loss. Calcif Tissue Int 1997;61:142-147.
5. Valente M, Bufalino L, Castiglione GN, et al. Effects of 1-year
treatment with ipriflavone on bone in postmenopausal women with low bone
mass. Calcif Tissue Int 1994;54:377-380.
6. Effect of ipriflavone on the response of uterus and thyroid to
estrogen. Life Sci 1986 Feb 24;38(8):757-764.
7. Yamazaki I, Kinoshita M. Calcitonin secreting property of
ipriflavone in the presence of estrogen. Life Sci 1986;38:1535-1541.
8. Arjmandi BH, Khalil DA, Hollis BW. Ipriflavone, a synthetic
phytoestrogen, enhances intestinal calcium transport In vitro. Calcif
Tissue Int. 2000 Sep;67(3):225-9.
9. Feuer L, Barath P, Strauss I, Kekes E. Experimental studies on the
cardiological effects of ipriflavone on the isolated rabbit heart and in
rat and dog. Arzneimittelforschung 1981;31(6):953-8.