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ISP diets with higher amounts of isoflavones depressed Table 8). Although the mechanism of action and the exact
serum cholesterol. However, removing isoflavones by bioactive components responsible for cholesterol reduction
alcohol washing the soy protein also removes other bioac- were unknown, FDA nevertheless approved a health claim
tives such as saponins that may affect lipid metabolism for the lipid-lowering capabilities of soy in 1999 (FDA,
(Erdman, 2000), so the role of isoflavones is difficult to 1999c).
Table 8. Case Study: Soy Protein and Coronary Heart Disease, continued
Hill Criteriaa Evidence Supporting/Against Studies Cited by FDA in FR References
Notice/ FDA Papers
Biologic gradient: evidence  The intervention studies suggest that a Bakhit et al., 1994; Baum et al., 63 FR 62989
of a dose-response curve minimum level of approximately 25 g of soy 1998; Bosello et al., 1988;
protein is needed to have a clinically significant Carroll et al., 1978; Crouse et al.,
effect on total and LDL cholesterol levels. 1999; Descovich et al., 1980;
Gaddi et al., 1991; Goldberg et
al., 1982; Jenkins et al., 1989;
Kurowska et al., 1997; Lovati et
al., 1987; Mercer et al., 1987;
Potter et al., 1993; Sirtori et al.,
1977, 1985; Van Raaij et al.,
1981; Verrilo et al., 1985; Wolfe
et al., 1981
 FDA agrees that the available data on the 64 FR 57712
hypocholesterolemic effects of soy protein do
not permit a dose-response assessment.
However, FDA notes that dose-response data
are not required to establish the qualifying
criteria for a substance that is the subject of a
health claim.
Plausibility: association is  Other comments reviewed various possible 64 FR 57709
biologically plausible mechanisms for the cholesterol-lowering effects
of soy protein and some argued that until the
mechanism of action of soy protein is clearly
established, no health claim should be
authorized. FDA notes, however, that such
knowledge is not necessarily required for
authorization of a health claim.
 The evidence shows a clear relationship 64 FR 57711
between soy protein and reduced risk of CHD
despite lack of a clearly defined mechanism for
its effect.
Coherence of explanation:  It is generally accepted that blood total and DHHS, 1988, 1990; FNB, 1989 63 FR 62979
association is consistent with LDL cholesterol levels can influence the risk of
current knowledge of the developing CHD, and, therefore, that dietary
disease/endpoint and factors affecting these blood cholesterol levels
biomarkers known to be affect the risk of CHD.
associated with it
a
Friis and Sellers, 1999.
Two additional Hill criteria (experiment and analogy) were not included in the table as FDA did not discuss them in their review of the data for the health claim, and the report from the
Keystone Center (1996) did not include them either.
Expert Report 39
Case Study: Efficacy of Stanols/Sterols et al., 1999). Evidence also indicates that phytosterols
influence the membrane proteins ABD-G5 and G8 (Berge
Phytosterols, widely distributed in the plant kingdom,
et al., 2000; Chen, 2001; Hendriks et al., 1999). While
significantly reduce serum LDL cholesterol and thus the
the exact mechanism is not clear, the effect of phytosterols
risk of cardiovascular disease (Law, 2000). The efficacy
in reducing cholesterol absorption is well established
of phytosterols has been demonstrated in scores of peer-
(Miettinen et al., 2000; von Bergmann et al., 1999). This
reviewed published studies (Jones and Raeini-Sarjaz, 2001;
reduction in cholesterol influx then reduces cholesterol
Ostlund, 2002).
availability for incorporation into LDL particles (Blom-
Structurally, phytosterols are closely related to choles-
quist et al., 1993; Hallikainen et al., 2000). The interfer-
terol. The scientific plausibility for the benefits of phy-
ence in cholesterol absorption has been demonstrated in
tosterols is well understood. Apparently, phytosterols
animal studies and in human trials (Jones and Raeini-
compete with cholesterol for incorporation of sterols into
Sarjaz, 2001; Ostlund, 2002).
micelles in the intestinal lumen, interfering with intestinal
Numerous well designed clinical studies have demon-
absorption of cholesterol, both dietary cholesterol and
endogenous cholesterol secreted into the intestinal lumen strated the cholesterol lowering properties of sterols and
(Jones et al., 2000; Normen et al., 2000; von Bergmann their hydrogenated derivatives, the stanol family of com-
Table 9. Case Study: Stanol/Sterol Esters and Coronary Heart Disease (FDA, 2000c)
Hill Criteriaa Evidence Supporting/Against Studies Cited by FDA in References
FR Notice/FDA Papers
Strength of association:  In most intervention trials in subjects with mildly to Hendriks et al., 1991; 65 FR 54700-
a strong association is moderately elevated cholesterol levels (total Jones et al., 2000; Maki et al., 54701
less likely to be the result cholesterol
of errors found to reduce blood total and/or LDL cholesterol (1 study); Jones et al., 1999;
levels to a significant degree. Weststrate and Meijer, 1998
Consistency upon  Four studies show a relationship between con- Hendriks et al., 1999; 65 FR 54692
repetition: association sumption of plant sterols and reduced blood Jones et al., 1999, 2000;
has been observed by cholesterol in hypercholesterolemic subjects Weststrate and Meijer,
different persons in consuming diets within the range of a typical 1998;
different places, American diet.
circumstances, and times
 The results of three studies support a cholesterol- Ayesh et al., 1999; Pelletier 65 FR 54694
lowering effect of plant sterols in subjects with et al., 1995; Sierksma et al.,
normal cholesterol values. 1999
 Two studies showed a relationship between Andersson et al., 1999; 65 FR 54695
consumption of plant stanol esters and reduced Hallikainen et al., 1999
blood cholesterol in hypercholesterolemic subjects
who consumed plant stanol esters as part of a low
saturated fat and low cholesterol diet.
 Eight studies show a relationship between Miettinen and Vanhanen, 65 FR 54696
consumption of plant stanols and reduced blood 1994; and Vanhanen and
total and LDL cholesterol in hypercholesterolemic Miettinen, 1992 (1 study);
subjects consuming diets with the range of a typical Blomqvist et al., 1993; [ Pobierz całość w formacie PDF ]
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