Calorie Restriction (CR) Diet


CR Biomarkers: People on CR see these physiological changes as reported in peer reviewed articles

July 5, 2006

How do you know that you are really on a CR diet and that it is having the intended effect? There are theoretical formulas for calorie intake, but what about a set of measurements you can take to see results? As far as I know, there is no standard set of measurements for that.

The following table lists human biomarker values which have been measured during recent CR studies and show a significant difference between CR and non-CR subjects. After the table is more information about it. A second table based on the Biosphere 2 study4 lists additional biomarkers which changed significantly for 8 subjects whose diet and biomarkers were carefully controlled and measured for 2 years from 1991 to 1993.

I also made a personal results table that lists my biomarker values next to those from these tables see if I am getting the expected results. For 17 out of 19 biomarkers I am.

For both of these tables, please read the original study refered to in the footnote references for a complete understanding of what is being measured.

CR Biomarker Values From Recent Peer Reviewed Studies

Biomarker Human
CR Value
Units Reference Range Control Group
Value
Monkey CR
Biomarker?
Non-Primate mammal
CR Biomarker?
T3
73.61
ng/dl
70 - 165 (study); 100-200 (NIH Medline)
91.01 (Sedentary) /
94.31 (Exercising)
mixed4
Yes4
FT3
1.08 (for subgroup, see study)1
pg/dl
1.45 - 3.48 (see study); 2-6 (WebMD)
1.681 (Sedentary subgroup)
n/a
n/a
hsCRP
0.231
mg/L
<1 ("lowest risk") of heart/vascular problems
1 - 3 ("average risk") (WebMD)
1.111 (Sedentary) /
0.651 (Exercising)
n/a
n/a
Fasting insulin level
[Drops by about
3 from baseline
of 9.4 after 6 months]3
IU/mL
5-20 (NIH Medline)
[Does not drop from baseline of 12.3 after 6 months]3
Mixed4
Yes4
Transforming Growth
Factor-Beta
29.42
ng/ml
n/a
35.42
n/a
n/a
tumor necrosis
factor-alpha
0.741
pg/ml
<25 Labcorp Test Standards [page search tumor n]
1.541 (Sedentary)
1.421 (Exercising)
n/a
n/a
Body Temperature
Dropped about 0.36 (24 hr average) in 6 months3
oF
97.6 - 98.8
Unchanged (24 hr average)3
n/a
n/a
Blood Pressure
102/612
Also see Table 2
mm Hg
<120 (Systolic)/<80 (Diastolic)(NIH Medline)
131/832
Yes4
Yes4

About The Table

The table is a work in progress and comments/suggestions are welcome. (Send to phillips@kcnet.com). I list only biomarkers where at least one recent study has shown a significant difference between CR and non-CR. The biomarker name links to a description at Lab Tests Online. For simplicity, I list only the average value from the study, not the range or standard deviations. I include a "reference range", as noted in the study, WebMD, and/or NIH Medline. Reference ranges vary based on several factors: how it was measured; the reference population; etc.

The table also notes if animals on CR show a significant difference from controls. Most of this information comes from the Biosphere 2 study4, which has the original references.

And, as always, consult with your own physician about the meaning of any test you take.

Biosphere 2 Biomarker Changes

The Biosphere 2 study4 tracked the diet and biomarkers for 8 subjects who agreed to live in Biosphere 2 for 2 years. The subjects were put on a CR diet. A large number of biomarkers were measured regularly to see how they changed, and then how they changed back following the 2 year study. The values shown in the table are the average values taken during the 3rd, 4th, and 5th periods inside the Biosphere. I computed the averages using these values because they were taken during the middle of the confinement.

They are limited to biomarkers which changed significantly with the study. They are listed as in Table 3 of the study from most signifant to less significant.

This study noted whether changes occurred in monkeys and non-primate mammals and, if so, the direction of change. I have indicated these as a change up, down, none, mixed, or n/a (not available). I have also highlighted in blue those biomarkers which changed in the same direction across all mammals. Refer to the study for more detail and references to supporting studies.

CR Biomarker Values From Biosphere 2 Study4

Biomarker Human
CR Value
Units Reference Range Monkey CR
Change
Non-Primate mammal
CR Change
BMI
19.3
kg/m2
18.5-25 (NHLBI)
n/a
n/a
Cholesterol
121.3
mg/dL
<200 (NIH Medline)
n/a
down
Triiodothyronine (T3)
See also Table 1
99.8
ng/dL
100 - 200 (NIH Medline)
n/a
down
Thyroid (or Thyroxine) binding globulin - TBG
14.9
g/mL
1024 (NIH Medline)
n/a
n/a
High-density lipoprotein
37.4
mg/dL
>40 (NIH Medline)
n/a
down
Systolic Blood Pressure
90.4
Hg(mm)
<120 (NIH Medline)
down
down
Insulin
8.0
mcU/dL
5 - 20 (NIH Medline)
down
down
Uric acid
3.8
mg/dL
<3 - 7 (NIH Medline))
down
mixed
Diastolic Blood Pressure
57.1
Hg(mm)
<80 (NIH Medline))
down
down
Androstenedione
145
ng/dL
Adults: male: 57-265, female: 47-268 (LabCorp)
n/a
n/a
Glycosylated hemoglobin (HbA1c)
6.1
percent
<5 (NIH Medline)
none
down
Alkaline phosphatase (ALP)
60.9
Units/L
44147 (NIH Medline)
up
up
Alanine transferase (ALT)
21.4
Units/L
4-36 (WebMD)
up
up
Reverse triiodothyronine (rT3)
31.1
ng/dL
n/a
n/a
up
Glucose
70.1
milligrams/dL
<100 (NIH Medline)
down
down
Transferin
230.9
mg/dL
n/a
n/a
n/a
Low density lipoprotein
66.8
mg/dL
<100 (NIH Medline)
none
n/a
Estradiol (men)
24.3
pg/dL
10 to 60 (NIH Medline)
n/a
n/a
Prolactin (men)
12.4
ng/dL
0-20 (NIH Medline)
n/a
n/a
Renin
0.8
(ng/mL)/h
1.9-3.7 (NIH Medline)
n/a
n/a
Blood urea nitrogen (BUN)
11.0
mg/dL
7-20 (NIH Medline)
n/a
n/a
Thyroid stimulating hormone (TSH)
2.1
mIU/L
0.4-4.0 (NIH Medline)
n/a
none
Cortisol binding globulin
3.2
mg/dL
n/a
down/none
[study was up]
down
[study was up]
White blood cell count (WBC)
5.1
103
4.5-10 NIH Medline
down
down
Sex hormone binding globuline
57.4
nmol/dL
n/a
n/a
none
Total cortisol
16.2
g/dL
6-23 NIH Medline
none
up
Prolactin (women)
15.0
ng/dL
0-20 (NIH Medline)
n/a
down
[study was up]
Free cortisol
2.1
g/dL
5-25 (Blood morning);
3-16 (Blood afternoon) (WebMD)
n/a
up
Creatinine
0.9
mg/dL
0.8-1.4 (NIH Medline)
n/a
none/down
Triglycerides
103.7
mg/dL
<150 (NIH Medline)
down
down

Biomarker References

1 Fontana Luigi, Klein Samuel, Holloszy John O, Premachandra Bhartur N. Effect of Long-term Calorie Restriction with Adequate Protein and Micronutrients on Thyroid Hormones; Journal of Clinical Endocrinology & Metabolism 2006, 10.1210/jc.2006-0328

2 Meyer Timothy E, Kovacs Sandor J, Ehsani Ali A, Klein Samuel, Holloszy John O, Fontana Luigi. Long-Term Caloric Restriction Ameliorates the Decline in Diastolic Function in Humans; Journal of the American College of Cardiology; Volume 47, Issue 2 , 17 January 2006, Pages 398-402

3 Heilbronn Leonie K, Jonge Lilian de, Frisard Madlyn I, DeLany James P, Larson-Meyer D. Enette, Rood Jennifer, Nguyen Tuong, Martin Corby K, Volaufova Julia, Most Marlene M, Greenway Frank L, Smith Steven R, Deutsch Walter A, Williamson Donald A, Ravussin Eric. Effect of 6-Month Calorie Restriction on Biomarkers of Longevity, Metabolic Adaptation, and Oxidative Stress in Overweight Individuals; Journal of the American Medical Association, April 5, 2006; JAMA. 2006;295:1539-1548, 1577-1578

4 Walford Roy L, Mock Dennis, Verdery Roy, MacCallum Calorie Restriction in Biosphere 2: Alterations in Physiologic, Hematologic, Hormonal, and Biochemical Parameters in Humans Restricted for a 2-Year Period; Journal of Gerontology: BIOLOGICAL SCIENCES 2002, Vol. 57A, No. 6, B211-B224

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