October 9, 2003

Dockets Management Branch (HFA-305)

Food and Drug Administration

5630 Fishers Lane, rm. 1061

Rockville, MD 20852

RE: \[Docket No. 03N-0076\]

Dear Sir/Madam:

The North American branch of the International Life Sciences Institute
(ILSI N.A.), respectfully submits the following comments directed to the
Federal Register notice on July 11, 2003 (68 FR 41507) regarding the
advance notice of proposed rulemaking (ANPR) on Food Labeling: *Trans*
Fatty Acids in Nutrition Labeling; Consumer Research to Consider
Nutrient Content Claims and Health Claims and Possible Footnote or
Disclosure Statements.

ILSI N.A., a public, non-profit scientific foundation, advances the
understanding and application of scientific issues related to the
nutritional quality and safety of the food supply, as well as health
issues related to consumer self-care products. The organization carries
out its mission by sponsoring relevant research programs, professional
education programs and workshops, seminars, and publications, as well as
providing a neutral forum for government, academic, and industry
scientists to discuss and resolve scientific issues of common concern
for the well-being of the general public. ILSI N.A.'s programs are
supported primarily by its industry membership.

The comments submitted address the request for information from
scientific bodies concerning *trans* fatty acids (TFA) in nutrition
labeling. In response to this request, members of the ILSI N.A.
Technical Committee on Dietary Lipids (ILSI Lipids Committee) reviewed
various intervention studies cited by the Food and Drug Administration
(FDA) in the final rule on Food Labeling: *Trans* Fatty Acids in
Nutrition labeling, Nutrient Content Claims, and Health Claims (68 FR
41434) and the proposed rule on Food Labeling: *Trans* Fatty Acids in
Nutrition labeling, Nutrient Content Claims, and Health Claims (64 FR
62746).

Data from 16 intervention trials were reviewed, in which 17
control/comparison (control) and 27 treatment TFA intake levels were
identified **(1-16)**. One study **(9)** not cited by FDA in the ANPR
has been included due to its inclusion in the Ascherio et al **(17)**
analysis. All fatty acid intakes, when not reported as %En, were
converted to %En, thereby permitting study comparisons on a similar
basis. Also, LDL-C and HDL-C values expressed as mg/dL were converted to
mM. The fatty acid intake and serum lipid data are summarized in **table
1**.

As a result of this review, ILSI N.A. respectfully submits that:

1)  There is sufficient variation in the intake levels of TFA and SFA,
    across the numerous intervention trials, to allow modeling of fatty
    acid intake and its impact on serum cholesterol levels;

2)  It does not seem possible to make a meaningful distinction between
    the intake of *trans* fatty acids and saturated fatty acids (SFA)
    with respect to any differential impact on LDL cholesterol (LDL-C);

3)  It does not seem possible to make a meaningful distinction between
    the intake of TFA and SFA with respect to any differential impact on
    HDL cholesterol (HDL-C), when TFA intake is less than 5% of total
    energy intake (5% En);

4)  Published data suggest that the 90^th^ percentile of TFA intake
    falls below 5%En in the North American diet ;

5)  The most effective manner to predict changes in serum cholesterol
    levels, explaining the majority of the variance, is to consider the
    sum of TFA and SFA intake.

These conclusions are based on observations of the dietary levels of TFA
and other fatty acids such as linoleic acid (LA) that were tested in the
intervention trials, their associations with serum LDL-C and HDL-C, and
how TFA intakes compare to those estimated from representative samples
of the U.S. population.

It must be acknowledged that differences exist among the studies in
design, objectives, test products, and populations, and that these
studies have not been subjected to a rigorous meta-analysis. ILSI N.A.
has undertaken to examine these studies through a thorough
meta-analysis, with completion expected in early December, 2003.

Nonetheless, these datasets represent controlled studies of the relation
between TFA intake, SFA intake, and serum lipids. As such conclusions
drawn from these observations may assist the FDA in deliberations
regarding TFA and food labeling.

-   **Sufficient variation in TFA, SFA, and LA intakes across
    intervention trials exists to model intake effects on serum lipids**

TFA intakes ranged from 0 to 10.9%En. Control TFA intakes in the
intervention studies ranged from 0 to 2.4%En, with 14 of 17 control TFA
intakes being less than 1%En. TFA added to the diet for treatment ranged
from 0 to 10.9%En, with 19 of 27 being greater than 3%En. The SFA and
linoleic acid (LA) intakes across and within studies also varied. In the
44 control plus treatment diets, SFA ranged from 3.1 to 22.9%En, with 23
diets containing 10%En or more and 16 diets containing between 7 and
10%En. LA ranged from 0.8 to 15.6%En, with 31 diets containing at least
4%En and 9 diets having at least 10%En.

Changes in intake (treatment minus control) ranged from -1.2 to +10.9%En
for TFA, -10.3 to +4.3%En for SFA, and -12.2 to +13.0%En for LA. The
changes in TFA intakes were associated with little change in SFA intake
(**figure 1)** but significant decreases in LA intakes **(figure 2**).

-   **Intake of TFA do not differentially impact serum LDL-C compared to
    similar intakes of SFA**

Figures 3 and 4, respectively, plot changes in TFA intake (%En) against
changes in LDL-C in relative (%) and absolute terms. Figures 5 and 6,
respectively, plot changes in SFA intake (%En) against changes in LDL-C
in relative (%) and absolute terms. There are two key points to note.
First, in all cases the slopes of the lines are similar. This strongly
suggests that the impact on serum LDL-C of TFA intake and SFA intake are
essentially indistinguishable. Second, higher order predictive equations
provide very little additional explanation of the variance, suggesting
that a linear regression is a reasonable model for these data (r^2^
coefficients are provided for first, second and fourth order equations
as examples, though the biological relevance of a fourth order equation
may be difficult to interpret).

In summary, the data do not permit a meaningful distinction between the
intake of *trans* fatty acids and saturated fatty acids (SFA) with
respect to any differential impact on LDL cholesterol (LDL-C).

-   **Intake of TFA do not differentially impact serum HDL-C compared to
    similar intakes of SFA, when TFA intakes are less than 5%En**

Figures 7 and 8, respectively, plot changes in TFA intake (%En) against
changes in HDL-C in relative (%) and absolute terms. However in contrast
to plots of LDL-C, higher order equations provide significantly greater
predictive value, explaining a greater proportion of the variance. Most
intriguing is the finding that there appears to be little impact on
serum HDL-C when TFA intake is less than 5% En, when a second or fourth
order equation is employed. Above this threshold, there is a clear
inverse relationship, with increasing TFA intakes resulting in decreased
serum HDL-C. Not surprisingly, a simple linear regression has negative
slope, but this is a poor model of the data.

SFA intake (%En) appears to show no such threshold effect on serum
HDL-C, in fact showing very little effect at all (figures 9 and 10).

In summary, the data do not permit a meaningful distinction between the
intake of TFA and SFA with respect to any differential impact on HDL
cholesterol (HDL-C), when TFA intake is less than 5% of total energy
intake (5% En).

-   **Mean population TFA intakes are below levels that significantly
    affect HDL-C**

The difficulties and limitations associated with estimating the TFA
intake of free-living individuals, as well as FDA's caution to avoid
over-interpreting dietary intake estimates and relationships to TFA
intake levels used in intervention trials, must be acknowledged. (68 FR
41434 at 41446) Nonetheless, we believe the following observations may
be useful to FDA in order to place these conclusions within the context
of the North American diet.

TFA intakes have been estimated from food disappearance and availability
data, diet records and food frequency questionnaires from various
populations, chemical analysis of formulated or duplicate diets, and
chemical analysis of adipose tissue. We believe that TFA intakes
estimated from the CSFII are useful for drawing observations because
they are derived from a representative sample of the U.S. population and
are based on 24-hour recalled food intake, with or without 2-day
recorded food intake. Energy intakes from the CSFII are likely to be
underestimated by approximately 20 to 40% **(18)**. However, the TFA
data expressed as %En represent a reasonable, if not conservative,
estimate of intake.

Allison et al estimated the mean TFA intake from the 1989-1990 CSFII for
the total U.S. population aged 3 years and older to be 2.6%En, and from
2.6 to 2.8%En across various age and gender groups **(18)**. FDA
estimated the mean TFA intake for adults to be 2.91%En from the
1994-1996 CSFII. (8 FR 41434 at 41468) These population mean intakes are
below the 5% En levels in the intervention trials associated with
significant decreases in HDL-C. In addition, further inspection of
Allison et al's results suggest that even the 90^th^ percentile intake
of TFA would fall below 5% En, in this population.

In summary, published data show that TFA intake, even at the 90^th^
percentile, fall below the 5% En threshold when TFA significantly, and
negatively, impact serum HDL-C.

-   **The sum of TFA and SFA intakes provides the most robust predictor
    of changes in serum LDL-C**

When TFA and SFA intakes are combined, the most robust predictor of
serum LDL-C is obtained, with an r^2^ coefficient approximately 0.83.
This is true when considering either relative (%) or absolute (mM)
changes in serum LDL-C (figures 11 and 12 respectively). It is once
again very interesting to note that higher order equations do not
provide any significant improvement in explaining the variance,
indicating that a linear regression presents a viable model of the data.

Since there is very little, if any, relation between SFA intake and
HDL-C in these intervention trials, and the same is true for TFA intake
below 5% En, summing the intake of these two fatty acids did not prove
to be an effective predictor of serum HDL-C.

In summary, TFA and SFA intakes, when considered together, prove to be
the most robust predictor of serum LDL-C.

-   **TFA and SFA intakes must be considered together when examining
    their impact on serum cholesterol levels, and one is not
    distinguishable from the other within the context of the North
    American diet**

In conclusion, ILSI N.A. respectfully suggests that the data reviewed
support the following:

1)  Sufficient data exists to model the impact of TFA and SFA intake on
    serum cholesterol levels;

2)  No meaningful distinction can be made between the intake of TFA and
    SFA with respect to impact on LDL-C;

3)  No meaningful distinction can be made between the intake of TFA and
    SFA with respect to impact on HDL-C, when TFA intake is less 5% En;

4)  Published data indicate that the 90^th^ percentile of TFA intake
    falls below 5% En

5)  The sum of TFA and SFA intake is the most effective predictor of
    changes in serum lipid profile, explaining the majority of the
    variance.

ILSI N.A. encourages FDA to consider the observations presented
regarding TFA and SFA intakes tested in intervention trials and how
these intakes relate to changes in the intakes of other fatty acids, to
changes in LDL-C and HDL-C, within the context of TFA intakes estimated
from representative samples of the U.S. population.

Sincerely,

Richard M. Black, Ph.D.

Executive Director, ILSI North America

**References**

1\. Aro A, Jauhiainen M, Partanen R, et al. Stearic acid, trans fatty
acids, and dairy fat: effects on serum and lipoprotein lipids,
apolipoproteins, lipoprotein(a), and lipid transfer proteins in healthy
subjects. Am J Clin Nutr 1997;65:1419-1426.

2\. de Roos NM, Bots ML, Katan MB. Replacement of dietary saturated
fatty acids by trans fatty acids lowers serum HDL cholesterol and
impairs endothelial function in healthy men and women. Arterioscler
ThrombVasc Biol 2001;21:1233-1237.

3\. Judd JT, Clevidence BA, Muesing RA, et al. Dietary trans fatty
acids: effects on plasma lipids and lipoproteins of healthy men and
women. Am J Clin Nutr 1994;59:861-868.

4\. Judd JT, Baer DL, Clevidence BA, et al. Dietary cis and trans
monounsaturated and saturated fatty acids and plasma lipids and
lipoproteins in men. Lipids 2002:37:123-131.

5\. Lichtenstein AH, Ausman LM, Carrasco W, et al. Hydrogenation impairs
the hypolipidemic effect of corn oil in humans. Hydrogenation, trans
fatty acids, and plasma lipids. Arterioscler Thromb 1993;13:154-161.

6\. Lichtenstein AH, Ausman LM, Jalbert SM, Schaefer EJ. Effects of
different forms of dietary hydrogenated fats on serum lipoprotein
cholesterol levels. N Eng J Med 1999;340:1933-1940.

7\. Mensink RP, Katan MB. Effect of dietary trans fatty acids on
high-density and low-density lipoprotein cholesterol levels in healthy
subjects. N Eng J Med 1990;323:439-445.

8\. Nestel PJ, Noakes M, Belling GB, et al. Plasma lipoprotein lipid and
Lp(a) changes with substitution of elaidic acid for oleic acid in the
diet. J Lipid Res 1992;33:1029-1036.

9\. Sundram K, Ismail A, Hayes KC, et. Al. Trans (Elaidic) fatty acids
adversely affect the lipoprotein profile relative to specific saturated
fatty acids in humans. J Nutr 1997;127:514S-520S.

10\. Wood R, Kubena K, Tseng S, et al. Effect of palm oil, margarine,
butter, and sunflower oil on the serum lipids and lipoproteins of
normocholesterolemic middle-aged men. J Nutr Biochem 1993;4:286-297.

11\. Zock PL, Katan MB. Hydrogenation alternatives: effects of trans
fatty acids and stearic acid versus linoleic acid on serum lipids and
lipoproteins in humans. J Lipid Res 1992;33:399-410.

12\. Almendingen K, Jordal O, Kierulf P, et al. Effects of partially
hydrogenated fish oil, partially hydrogenated soybean oil, and butter on
serum lipoproteins and Lp(a) in men. J Lipid Res 1995;36:1370-1384.

13\. Denke MA, Adams-Huet B, Nguyen BS. Individual cholesterol variation
in response to a margarine- or butter-based diet\--a study in families.
JAMA 2000;284: 2740-2747.

14\. Judd JT, Baer DJ, Clevidence BA, et al. Effects of margarine
compared with those of butter on blood lipid profiles related to
cardiovascular disease risk factors in normolipemic adults fed
controlled diets. Am J Clin Nutr 1998:68:768-777.

15\. Noakes M, Clifton PM. Oil blends containing partially hydrogenated
or interesterified fats: differential effects on plasma lipids. Am J
Clin Nutr 1998;68:242-247.

16\. Wood R, Kubena K, O\'Brien B, et al. Effect of butter, mono- and
polyunsaturated fatty acid-enriched butter, trans fatty acid margarine,
and zero trans fatty acid margarine on serum lipids and lipoproteins in
healthy men. J Lipid Res 1993;34:1-11.

17\. Ascherio A, Katan MB, Zock PL, et al. Trans fatty acids and
coronary heart disease. N Eng J Med 1999;340:1994-1998.

18\. Allison DB, Egan SK, Barraj LM, et al. Estimated intakes of
trans-fatty acid and other fatty acids by the U.S. population. J Am Diet
Assoc 1999;99:166-174.

.

> Table 1. Fatty Acid Intakes and Serum LDL Cholesterol and HDL
> Cholesterol

<table>
<colgroup>
<col style="width: 14%" />
<col style="width: 12%" />
<col style="width: 5%" />
<col style="width: 5%" />
<col style="width: 5%" />
<col style="width: 5%" />
<col style="width: 5%" />
<col style="width: 5%" />
<col style="width: 5%" />
<col style="width: 5%" />
<col style="width: 6%" />
<col style="width: 7%" />
<col style="width: 6%" />
<col style="width: 7%" />
</colgroup>
<thead>
<tr class="header">
<th colspan="14">Table 1. Fatty Acid Intakes and Serum LDL Cholesterol
and HDL Cholesterol</th>
</tr>
<tr class="odd">
<th>Reference</th>
<th>Treatment</th>
<th><p>TFA</p>
<p>(%En)</p></th>
<th><p>SFA</p>
<p>(%En)</p></th>
<th><p>LA</p>
<p>(%En)</p></th>
<th><p>LDL-C</p>
<p>(mM)</p></th>
<th><p>HDL-C</p>
<p>(mM)</p></th>
<th><p>∆ TFA</p>
<p>(%En)</p></th>
<th><p>∆ SFA</p>
<p>(%En)</p></th>
<th><p>∆ LA</p>
<p>(%En)</p></th>
<th><p>∆ LDL-C</p>
<p>(mM)</p></th>
<th><p>∆ HDL-C</p>
<p>(mM)</p></th>
<th><p>∆ LDL-C</p>
<p>(%)</p></th>
<th><p>∆ HDL-C</p>
<p>(%)</p></th>
</tr>
</thead>
<tbody>
<tr class="odd">
<td>Aro 1997 (1)</td>
<td>TFA</td>
<td>8.7</td>
<td>7.1</td>
<td>2.7</td>
<td>3.13</td>
<td>1.22</td>
<td>8.3</td>
<td>-7.9</td>
<td>-0.4</td>
<td>0.24*</td>
<td>-0.20*</td>
<td>8.3*</td>
<td>-14.1*</td>
</tr>
<tr class="even">
<td> </td>
<td>STE†</td>
<td>0.4</td>
<td>15.0</td>
<td>3.1</td>
<td>2.89</td>
<td>1.42</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>De Roos 2001</td>
<td>TFA</td>
<td>9.2</td>
<td>12.9</td>
<td>4.1</td>
<td>3.04</td>
<td>1.48</td>
<td>8.9</td>
<td>-10.0</td>
<td>-1.8</td>
<td>-0.01</td>
<td>-0.39*</td>
<td>-0.3</td>
<td>-20.9*</td>
</tr>
<tr class="even">
<td> </td>
<td>SFA†</td>
<td>0.3</td>
<td>22.9</td>
<td>5.9</td>
<td>3.05</td>
<td>1.87</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Judd 1994 (3)</td>
<td>TFA (moderate)</td>
<td>3.8</td>
<td>13.0</td>
<td>6.0</td>
<td>3.54</td>
<td>1.40</td>
<td>3.1</td>
<td>-0.4</td>
<td>-0.1</td>
<td>0.20*</td>
<td>-0.02</td>
<td>6.0*</td>
<td>-1.4</td>
</tr>
<tr class="even">
<td></td>
<td>TFA (high)</td>
<td>6.6</td>
<td>12.7</td>
<td>6.2</td>
<td>3.60</td>
<td>1.38</td>
<td>5.9</td>
<td>-0.7</td>
<td>0.1</td>
<td>0.26*</td>
<td>-0.04*</td>
<td>7.8*</td>
<td>-2.8*</td>
</tr>
<tr class="odd">
<td> </td>
<td>OL†</td>
<td>0.7</td>
<td>13.4</td>
<td>6.1</td>
<td>3.34</td>
<td>1.42</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Judd 2002 (4)</td>
<td>TFA (moderate)</td>
<td>4.2</td>
<td>16.9</td>
<td>4.3</td>
<td>3.32</td>
<td>1.17</td>
<td>4.1</td>
<td>4.3</td>
<td>0.5</td>
<td>0.37*</td>
<td>-0.07*</td>
<td>12.5*</td>
<td>-5.6*</td>
</tr>
<tr class="odd">
<td></td>
<td>TFA (high)</td>
<td>8.3</td>
<td>12.9</td>
<td>4.0</td>
<td>3.36</td>
<td>1.16</td>
<td>8.2</td>
<td>0.3</td>
<td>0.2</td>
<td>0.41*</td>
<td>-0.08*</td>
<td>13.9*</td>
<td>-6.5*</td>
</tr>
<tr class="even">
<td> </td>
<td>OL†</td>
<td>0.1</td>
<td>12.6</td>
<td>3.8</td>
<td>2.95</td>
<td>1.24</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Lichtenstein 1993 (5)</td>
<td>Margarine</td>
<td>4.2</td>
<td>7.7</td>
<td>7.9</td>
<td>3.49</td>
<td>1.11</td>
<td>3.8</td>
<td>1.3</td>
<td>-0.6</td>
<td>0.26#</td>
<td>-0.03</td>
<td>8.0#</td>
<td>-2.6</td>
</tr>
<tr class="even">
<td> </td>
<td>CO†</td>
<td>0.4</td>
<td>6.4</td>
<td>8.5</td>
<td>3.23</td>
<td>1.14</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Lichtenstein 1999 (6)</td>
<td>Semiliquid margarine</td>
<td>0.9</td>
<td>8.6</td>
<td>12.1</td>
<td>4.01</td>
<td>1.11</td>
<td>0.3</td>
<td>1.3</td>
<td>1.4</td>
<td>0.03</td>
<td>0.00</td>
<td>0.8</td>
<td>0.0</td>
</tr>
<tr class="even">
<td></td>
<td>Butter</td>
<td>1.3</td>
<td>16.7</td>
<td>2.1</td>
<td>4.58</td>
<td>1.16</td>
<td>0.7</td>
<td>9.4</td>
<td>-8.6</td>
<td>0.60*</td>
<td>0.05</td>
<td>15.1*</td>
<td>4.5</td>
</tr>
<tr class="odd">
<td></td>
<td>Soft margarine</td>
<td>3.3</td>
<td>8.4</td>
<td>10.0</td>
<td>4.11</td>
<td>1.11</td>
<td>2.7</td>
<td>1.1</td>
<td>-0.7</td>
<td>0.13</td>
<td>0.00</td>
<td>3.3</td>
<td>0.0</td>
</tr>
<tr class="even">
<td></td>
<td>Shortening</td>
<td>4.2</td>
<td>8.6</td>
<td>7.2</td>
<td>4.24</td>
<td>1.11</td>
<td>3.6</td>
<td>1.3</td>
<td>-3.5</td>
<td>0.26*</td>
<td>0.00</td>
<td>6.5*</td>
<td>0.0</td>
</tr>
<tr class="odd">
<td></td>
<td>Stick margarine</td>
<td>6.7</td>
<td>8.5</td>
<td>5.6</td>
<td>4.34</td>
<td>1.09</td>
<td>6.1</td>
<td>1.2</td>
<td>-5.1</td>
<td>0.36*</td>
<td>-0.02</td>
<td>9.0*</td>
<td>-1.8</td>
</tr>
<tr class="even">
<td> </td>
<td>SBO†§</td>
<td>0.6</td>
<td>7.3</td>
<td>10.7</td>
<td>3.98</td>
<td>1.11</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Mensink 1990 (7)</td>
<td>TFA</td>
<td>10.9</td>
<td>10.0</td>
<td>4.2</td>
<td>3.04</td>
<td>1.25</td>
<td>10.9</td>
<td>0.5</td>
<td>0.2</td>
<td>0.37*</td>
<td>-0.17*</td>
<td>13.9*</td>
<td>-12.0*</td>
</tr>
<tr class="even">
<td> </td>
<td>OL†</td>
<td>0.0</td>
<td>9.5</td>
<td>4.0</td>
<td>2.67</td>
<td>1.42</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Nestel 1992 (8)</td>
<td>TFA</td>
<td>6.7</td>
<td>10.0</td>
<td>6.6</td>
<td>4.27</td>
<td>0.98</td>
<td>4.3</td>
<td>1.0</td>
<td>1.3</td>
<td>0.37*</td>
<td>0.00</td>
<td>9.5*</td>
<td>0.0</td>
</tr>
<tr class="even">
<td> </td>
<td>OL†</td>
<td>2.4</td>
<td>9.0</td>
<td>5.3</td>
<td>3.90</td>
<td>0.98</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Sundram 1997 (9)</td>
<td>TFA</td>
<td>6.9</td>
<td>7.4</td>
<td>5.3</td>
<td>3.81</td>
<td>1.05</td>
<td>6.9</td>
<td>-2.1</td>
<td>1.4</td>
<td>0.64*</td>
<td>-0.20*</td>
<td>20.2*</td>
<td>-16.0*</td>
</tr>
<tr class="even">
<td> </td>
<td>OL†</td>
<td>0.0</td>
<td>9.5</td>
<td>3.9</td>
<td>3.17</td>
<td>1.25</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Wood 1993 (10)</td>
<td>Hard margarine</td>
<td>6.3</td>
<td>5.0</td>
<td>3.4</td>
<td>3.36</td>
<td>1.00</td>
<td>6.3</td>
<td>1.9</td>
<td>-12.2</td>
<td>0.13</td>
<td>0.00</td>
<td>4.0</td>
<td>0.0</td>
</tr>
<tr class="even">
<td> </td>
<td>SO†</td>
<td>0.0<sup>a</sup></td>
<td>3.1</td>
<td>15.6</td>
<td>3.23</td>
<td>1.00</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Zock 1992 (11)</td>
<td>TFA</td>
<td>7.7</td>
<td>10.3</td>
<td>3.8</td>
<td>3.07</td>
<td>1.37</td>
<td>7.6</td>
<td>-0.7</td>
<td>-8.2</td>
<td>0.24*</td>
<td>-0.10*</td>
<td>8.5*</td>
<td>-6.8*</td>
</tr>
<tr class="even">
<td> </td>
<td>LA†</td>
<td>0.1</td>
<td>11.0</td>
<td>12.0</td>
<td>2.83</td>
<td>1.47</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Almendingen 1995 (12)</td>
<td>PHSBO</td>
<td>8.5</td>
<td>11.0</td>
<td>5.4</td>
<td>3.58</td>
<td>1.05</td>
<td>7.6</td>
<td>-5.4</td>
<td>0.0</td>
<td>-0.23*</td>
<td>0.00</td>
<td>-6.0*</td>
<td>0.0</td>
</tr>
<tr class="even">
<td></td>
<td>PHFO</td>
<td>8.0</td>
<td>11.3</td>
<td>5.3</td>
<td>3.94</td>
<td>0.98</td>
<td>7.1</td>
<td>-5.1</td>
<td>-0.1</td>
<td>0.13</td>
<td>-0.07</td>
<td>3.4</td>
<td>-6.7*</td>
</tr>
<tr class="odd">
<td></td>
<td>Butter†</td>
<td>0.9</td>
<td>16.4</td>
<td>5.4</td>
<td>3.81</td>
<td>1.05</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Denke 2000 (13)</td>
<td>Margarine</td>
<td>1.5<sup>b</sup></td>
<td>9.0</td>
<td>10.0<sup>c</sup></td>
<td>3.00</td>
<td>1.19</td>
<td>1.0</td>
<td>-7.0</td>
<td>7.0</td>
<td>-0.39*</td>
<td>0.00</td>
<td>-11.5*</td>
<td>0.0</td>
</tr>
<tr class="odd">
<td> </td>
<td>Butter†</td>
<td>0.5</td>
<td>16.0</td>
<td>3.0</td>
<td>3.39</td>
<td>1.19</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Judd 1998 (14)</td>
<td>TFA margarine</td>
<td>3.9<sup>d</sup></td>
<td>7.9<sup>d</sup></td>
<td>2.7<sup>d</sup></td>
<td>3.27</td>
<td>1.24</td>
<td>1.2</td>
<td>-3.3</td>
<td>1.6</td>
<td>-0.17*</td>
<td>-0.03</td>
<td>-4.9*</td>
<td>-2.4</td>
</tr>
<tr class="odd">
<td></td>
<td>PUFA margarine</td>
<td>2.4<sup>d</sup></td>
<td>8.3<sup>d</sup></td>
<td>4.9<sup>d</sup></td>
<td>3.21</td>
<td>1.24</td>
<td>-0.3</td>
<td>-2.9</td>
<td>3.8</td>
<td>-0.23*</td>
<td>-0.03</td>
<td>-6.7*</td>
<td>-2.4</td>
</tr>
<tr class="even">
<td> </td>
<td>Butter†</td>
<td>2.7<sup>d</sup></td>
<td>11.2<sup>d</sup></td>
<td>1.1<sup>d</sup></td>
<td>3.44</td>
<td>1.27</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Noakes 1998 (15)</td>
<td>Canola+TFA</td>
<td>2.1<sup>d</sup></td>
<td>8.9<sup>d</sup></td>
<td>5.8<sup>cd</sup></td>
<td>3.64</td>
<td>1.19</td>
<td>1.4</td>
<td>-6.6</td>
<td>3.0</td>
<td>-0.50*</td>
<td>-0.01</td>
<td>-12.1*</td>
<td>-0.8</td>
</tr>
<tr class="even">
<td></td>
<td>Canola-TFA</td>
<td>0.0<sup>d</sup></td>
<td>8.7<sup>d</sup></td>
<td>6.0<sup>cd</sup></td>
<td>3.61</td>
<td>1.28</td>
<td>-0.7</td>
<td>-6.8</td>
<td>3.2</td>
<td>-0.53*</td>
<td>0.08</td>
<td>-12.8*</td>
<td>6.7</td>
</tr>
<tr class="odd">
<td> </td>
<td>Butter†</td>
<td>0.7<sup>d</sup></td>
<td>15.5<sup>d</sup></td>
<td>2.8<sup>cd</sup></td>
<td>4.14</td>
<td>1.20</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td>Noakes 1998 (15)</td>
<td>PUFA+TFA</td>
<td>2.1<sup>d</sup></td>
<td>10.2<sup>d</sup></td>
<td>10.4<sup>cd</sup></td>
<td>4.23</td>
<td>1.17</td>
<td>1.4</td>
<td>-7.5</td>
<td>7.3</td>
<td>-0.47*</td>
<td>-0.10</td>
<td>-10.0*</td>
<td>-7.9</td>
</tr>
<tr class="odd">
<td></td>
<td>PUFA-TFA</td>
<td>0.0<sup>d</sup></td>
<td>10.3<sup>d</sup></td>
<td>10.5<sup>cd</sup></td>
<td>3.98</td>
<td>1.23</td>
<td>-0.7</td>
<td>-7.4</td>
<td>7.4</td>
<td>-0.72*</td>
<td>-0.04</td>
<td>-15.3*</td>
<td>-3.1</td>
</tr>
<tr class="even">
<td> </td>
<td>Butter†</td>
<td>0.7 <sup>d</sup></td>
<td>17.7<sup>d</sup></td>
<td>3.1<sup>cd</sup></td>
<td>4.70</td>
<td>1.27</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="odd">
<td>Wood 1993 (16)</td>
<td>Hard margarine</td>
<td>6.7<sup>d</sup></td>
<td>5.0<sup>d</sup></td>
<td>0.8<sup>d</sup></td>
<td>3.47</td>
<td>1.16</td>
<td>5.5</td>
<td>-10.3</td>
<td>0.0</td>
<td>-0.31*</td>
<td>-0.06</td>
<td>-8.2*</td>
<td>-4.9</td>
</tr>
<tr class="even">
<td></td>
<td>Soft margarine</td>
<td>0.0<sup>d</sup></td>
<td>5.0<sup>d</sup></td>
<td>13.8<sup>d</sup></td>
<td>3.26</td>
<td>1.16</td>
<td>-1.2</td>
<td>-10.3</td>
<td>13.0</td>
<td>-0.52*</td>
<td>-0.06</td>
<td>-13.8*</td>
<td>-4.9</td>
</tr>
<tr class="odd">
<td> </td>
<td>Butter†φ</td>
<td>1.2<sup>d</sup></td>
<td>15.3<sup>d</sup></td>
<td>0.9<sup>d</sup></td>
<td>3.78</td>
<td>1.22</td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
<td></td>
</tr>
<tr class="even">
<td colspan="14"><p>Abbreviations: TFA, trans fatty acids; SFA,
saturated fatty acids; LA, linoleic acid; LDL-C, LDL cholesterol; HDL-C,
HDL cholesterol; %En, percent of energy; STE, stearic acid; OL, oleic
acid; SBO, soybean oil; SO, sunflower oil; PHSBO, partially hydrogenated
soybean oil; PHFO, partially hydrogenated fish oil; PUFA,
polyunsaturated fatty acid</p>
<p>* p ≤ 0.05</p>
<p>† Comparison diet</p>
<p># p&lt; 0.058</p>
<p>§ Authors used butter as the control diet. For this analysis,
treatments were compared to SBO</p>
<p>φ Authors compared test fats with each other. For this analysis, test
fats were compared to butter</p>
<p><sup>a</sup> Not reported for nontest fat foods common to all
diets</p>
<p><sup>b</sup> Fatty acid intakes based on 3-day food records</p>
<p><sup>c</sup> Total PUFA</p>
<p><sup>d</sup> Fatty acid values apply to test fat, not total fatty
acids in diet</p></td>
</tr>
</tbody>
</table>

![](media/image1.wmf){width="5.333333333333333in"
height="3.2395833333333335in"}

Figure 1. Change in saturated fatty acid intake vs. change in trans
fatty acid intake from treatments listed in table 1.

![](media/image2.wmf){width="5.34375in" height="3.4006944444444445in"}

Figure 2. Change in linoleic acid intake vs. change in trans fatty acid
intake from treatments listed in table 1.

![](media/image3.wmf){width="5.333333333333333in"
height="3.2395833333333335in"}

Figure 3. Percent change in LDL cholesterol vs. change in trans fatty
acid intake from treatments listed in table 1. Lines plotted represent
first, second and fourth order equations, with r^2^ coefficients
presented in that order.

![](media/image4.wmf){width="5.354166666666667in"
height="3.2604166666666665in"}

Figure 4. Absolute change in LDL cholesterol vs. change in trans fatty
acid intake from treatments listed in table 1. Lines plotted represent
first, second and fourth order equations, with r^2^ coefficients
presented in that order.

![](media/image5.wmf){width="5.354166666666667in"
height="3.2708333333333335in"}

Figure 5. Percent change in LDL cholesterol vs. change in saturated
fatty acid intake from treatments listed in table 1. Lines plotted
represent first, second and fourth order equations, with r^2^
coefficients presented in that order.

![](media/image6.wmf){width="5.364583333333333in"
height="3.2604166666666665in"}

Figure 6. Absolute change in LDL cholesterol vs. change in saturated
fatty acid intake from treatments listed in table 1. Lines plotted
represent first, second and fourth order equations, with r^2^
coefficients presented in that order.

![](media/image7.wmf){width="5.375in" height="3.25in"}

Figure 7. Percent change in HDL cholesterol vs. change in trans fatty
acid intake from treatments listed in table 1. Lines plotted represent
first, second and fourth order equations, with r^2^ coefficients
presented in that order.

![](media/image8.wmf){width="5.354166666666667in"
height="3.2395833333333335in"}

Figure 8. Absolute change in HDL cholesterol vs. change in trans fatty
acid intake from treatments listed in table 1. Lines plotted represent
first, second and fourth order equations, with r^2^ coefficients
presented in that order.

![](media/image9.wmf){width="5.354166666666667in"
height="3.2604166666666665in"}

Figure 9. Percent change in HDL cholesterol vs. change in saturated
fatty acid intake from treatments listed in table 1. Lines plotted
represent first, second and fourth order equations, with r^2^
coefficients presented in that order.

![](media/image10.wmf){width="5.34375in" height="3.2708333333333335in"}

Figure 10. Absolute change in HDL cholesterol vs. change in saturated
fatty acid intake from treatments listed in table 1. Lines plotted
represent first, second and fourth order equations, with r^2^
coefficients presented in that order.

![](media/image11.wmf){width="5.3125in" height="3.2708333333333335in"}

Figure 11. Percent change in HDL cholesterol vs. change in sum of trans
and saturated fatty acid intake from treatments listed in table 1. Lines
plotted represent first, second and fourth order equations, with r^2^
coefficients presented in that order.

![](media/image12.wmf){width="5.364583333333333in"
height="3.2604166666666665in"}

Figure 12. Absolute change in HDL cholesterol vs. change in sum of trans
and saturated fatty acid intake from treatments listed in table 1. Lines
plotted represent first, second and fourth order equations, with r^2^
coefficients presented in that order.