[PHNUTR-L] An Increase in Dietary N-3 Fatty Acids Decreases a Marker of Bone Resorption in Humans

[Kathrynne Holden]

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Bone Resorption and Omega-3 Fatty Acids
Rebecca Corwin, RD, PhD
Nutritional Sciences Department
The Pennsylvania State University
126 S. Henderson
University Park, PA 16802
  (814) 865-6519 / (814) 863-6103 (FAX)
  rxc13 at psu.edu
http://www.vitasearch.com/CP/experts/RCorwinAT02-21-07.htm

“An Increase in Dietary N-3 Fatty Acids Decreases a Marker of Bone 
Resorption in Humans,”

Nutr J, 2007 Jan 16;6(1):2 [Epub ahead of print] 45647 (3/2007)

Kirk Hamilton:         Can you please share with us your educational 
background and current position?



Rebecca Corwin:      I received my BA in Education, University of 
Florida, 1972; BS in Clinical Dietetics, Texas Woman’s University, 1978; 
MS in Biopsychology, University of Houston-Clear Lake, 1981; and PhD in 
Biopsychology, University of Chicago, 1989.



KH:    What got you interested in studying the role of plant omega-3 
fatty acids and bone loss?



RC:    Converging evidence suggested a beneficial effect of omega-3 
fatty acids on bone health, but very little was known about the 
plant-derived omega-3s. Furthermore, a controlled feeding study in 
humans had never been done. By conducting this kind of study, we knew 
exactly what the participants ate. This made it easier to determine what 
contributed to the beneficial effect.

KH:    Why did you not use fish oil (eicosapentaenoic (EPA) and 
docosahexaenoic (DHA)) as your source of omega-3s versus ALA 
(alpha-linolenic acid) from walnuts and flaxseed?

RC:    Previous studies had shown beneficial effects of marine-based 
omega-3 fatty acids (EPA, DHA) on bone health, but little was known 
about the effects of plant-based sources. The omega-3 fatty acid in 
plants (ALA) can be converted to EPA and DHA in the body, albeit not 
very efficiently. Since we wanted to use whole food sources instead of 
oil supplements, and many Americans do not like to eat fish, we decided 
to assess the effects of the plant-derived omega-3s in this study.

KH:    How much of bone loss is an inflammatory condition?

RC:    The importance of inflammation to bone loss varies according to 
the individual case. Inflammation probably plays a major role in bone 
pathology associated with inflammatory conditions such as rheumatoid 
arthritis and systemic lupus erythematosus, but may be important in 
conditions such as post-menopausal osteoporosis, as well.

KH:    What markers do you follow with regards to inflammation and bone 
loss?

RC:    Several markers of inflammation have been associated with bone 
loss including, but not limited to, TNF-alpha, interleukin-1 and 
interleukin-6.

KH:    Can you explain what the NTx (N-Telopeptide) test is and why it 
is valuable as a marker of bone loss?

RC:    Bone is made of several different types of cells including 
osteoblasts (bone forming cells), osteoclasts (bone breakdown or 
resorbing cells), and collagen (a protein matrix within which the 
osteoclasts and osteoblasts are located). Healthy bone is constantly 
being broken down and built back up again, a process that keeps bone 
strong. However, when breakdown exceeds formation, bones become weak and 
bone disease occurs. When the osteoclasts break bone down, some of the 
collagen is also dissolved. NTx is a product that is produced when the 
collagen is broken down.

KH:    What were the main differences between the Average American Diet 
(AAD), the Linoleic Acid Diet (LA) and the Alpha-Linolenic Acid Diets 
(ALA) with regards to fatty content? Was total fat content the same?

RC:    The LA and ALA diet contained a higher percentage of total fat 
compared to the AAD diet. However, the LA and ALA diets were higher in 
polyunsaturated fatty acids (PUFA) and lower in saturated fatty acids 
than the AAD. The ALA diet contained the highest amount of alpha 
linolenic acid (the plant-based omega-3 fatty acid), compared to the 
other two test diets.

KH:    Were more walnuts and flaxseed consumed in the ALA diet or were 
these fatty acids consumed in oils? How did you get the quantity you 
desired? Were the “fatty acids” given with meals or away from meals? In 
single doses or divided doses?

RC:    Walnuts and walnut oil, which are particularly rich sources of 
both n-6 and n-3 PUFA, represented half of the total fat in the LA and 
ALA diets. Sources of walnuts in the diet included walnut granola, honey 
walnut butter, walnut pesto, and plain walnuts as a snack. Flaxseed oil, 
also was used to increase the ALA content of the ALA Diet. The fatty 
acids were incorporated into the food that the subjects ate; they were 
not given as supplements. For each of the three experimental diets, 
eight calorie levels (1800 - 3900 kcal) were developed to meet different 
energy needs of the subjects. Unit foods (muffins) containing the same 
macronutrient profile of each of the test diets were used during each 
diet period to provide incremental adjustments of 100 kcal/day as needed 
to maintain body weight.

KH:    Can you tell us about your study and the basic results?

RC:    Subjects (n=23) consumed each diet for 6 weeks in a randomized, 
3-period crossover design. NTx levels were significantly lower following 
the ALA diet relative to the AAD. There was no change in levels of a 
marker of bone formation across the three diets. Concentrations of NTx 
were positively related to the pro-inflammatory cytokine TNF alpha for 
all three diets. The results indicate that plant sources of dietary n-3 
PUFA may have a protective effect on bone metabolism via a decrease in 
bone resorption in the presence of consistent levels of bone formation.

KH:    Were there any side effects to the different fatty acid diets? 
How was the patient compliance?

RC:    No side effects were reported. Patient compliance was excellent.

KH:    Are there any other components of flaxseed or walnut oils, aside 
from their omega-3 fatty acid content, that might account for this 
“bone-sparing effect?”

RC:    Flaxseed is also a source of lignans, a type of phytoestrogen, 
and walnuts have a high antioxidant content; however, the effects of 
these compounds on bone health have not been fully determined.

KH:    How would you incorporate your findings on these omega-3 fatty 
acids into public health recommendations for the prevention and/or 
reversal of bone loss that frequently include calcium, magnesium, zinc, 
copper, manganese, vitamin D, vitamin K, weight-bearing exercise and 
strength training recommendations?

RC:    Our findings are really too preliminary for public health 
recommendations to be made. However, the results of our study certainly 
are consistent with recommendations already in place for prevention of 
heart disease, i.e. to include sources of omega-3 fatty acids in your diet.

KH:    How often would you recommend the NTx test over a year or between 
DEXA tests, and what level are you trying to lower this marker to 
document success in slowing or preventing bone loss?

RC:    Bone density measurements, such as the DEXA scan, provide 
information about the current skeletal mass, but do not provide 
information about metabolic activity. One of the most commonly used 
markers to assess bone turnover is the serum NTx measurement. Various 
studies have shown that for a 1 SD increase in a bone marker value above 
that of a premenopausal woman, there is a 1.5 to 2.5-fold increase in 
bone loss over the next year. Therefore, the higher the bone marker 
(i.e. serum NTx), the greater the risk of bone loss over the next year. 
The goal in a patient with osteoporosis is to drive the NTx below these 
values, to a NTx seen in premenopausal women. Bone markers can also be 
used to monitor therapy for osteoporosis. This has been demonstrated for 
hormone replacement therapy, bisphosphonates, calcitonin, and the 
selective estrogen receptor modulators. As far as how often this test 
should be done, that would really be up to your doctor. The tests we ran 
are not the only tests for bone breakdown and build-up. Your doctor can 
recommend which tests would be best for you.

KH:    Is it worth doing fatty acid profiles on bone loss patients to 
assess for omega-3 fatty acid status? Were any fatty acids profiles done 
in this study? Did they correlate with bone loss or inflammation?

RC:    Fatty acid profiles are not used clinically to assess bone 
status. It is important to appreciate that plasma fatty acids represent 
short-term dietary consumption practices. Consequently since people 
don’t eat exactly the same thing day after day, the plasma profiles 
would not be informative of tissue or bone levels of fatty acids over 
the long term, and it is likely that these longer-term changes in the 
bone levels are what’s important. Serum fatty acids were assessed in 
this study, with the omega-3 fatty acids being highest when the ALA diet 
was consumed. They did not correlate strongly with the NTx; however, 
other work from Dr. Kris-Etherton’s group has shown correlations with 
markers of inflammation.

KH:    Do you have any further comments you would like to make on this 
interesting subject? This work is so important!

RC:    Most of the participants in this study were middle-aged men. The 
presence of osteoporosis in men is increasing, but they generally are 
not included in studies of bone health. This report, as well as others, 
suggests that men may benefit from adjustments to the fatty acid 
composition of the diet, not only because of benefits to their 
cardiovascular systems, but also because of benefits to their bones.
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
"Ask the Parkinson Dietitian"  http://www.parkinson.org/
"Eat well, stay well with Parkinson's disease"
"Parkinson's disease: Guidelines for Medical Nutrition Therapy"
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