Purdue News

July 11, 2005

Balance of essential fats may prevent bone loss after menopause

WEST LAFAYETTE, Ind. - Maintaining a proper balance of dietary fats may ward off much of the bone loss associated with post-menopausal osteoporosis, according to a recent study by scientists at Purdue University and the Indiana University School of Medicine.

The researchers found that diets with a low ratio of omega-6 fatty acids to omega-3 fatty acids minimized the bone loss typically brought on by estrogen deficiency, which is common in post-menopausal females. Omega-6 fatty acids are typically found in foods such as grains and beef, while omega-3 fatty acids are found in foods such as walnuts and salmon.

"Our lab and others have shown that omega-3 fatty acids help promote bone formation," said Bruce Watkins, professor and director of Purdue's Center for Enhancing Foods to Protect Health. "We also have shown that higher intakes of omega-6 fatty acids lead to an increased production of compounds associated with bone loss."

The current study, which is in press in the Journal of Nutritional Biochemistry, assessed bone mineral content and bone mineral density in female rats. These measurements are used as indicators of bone mass and bone strength, respectively.

Half the rats in the study had their ovaries removed, a procedure that leads to a rapid drop in estrogen levels. This mimics menopause and is the standard model for studying compounds that mitigate osteoporosis, said Mark Seifert, a professor of anatomy and cell biology at the Indiana University School of Medicine and the study's co-author.

"Bone loss due to estrogen depletion in the adult female rat is very similar to that which occurs in post-menopausal women," he said. "Studies like this will help us and other researchers assess drugs or nutraceuticals that may reduce the bone loss that sets in with menopause, " he said.

In the study, groups of these rats were fed diets containing different ratios of omega-6 to omega-3 polyunsaturated fatty acids.

While both types of fats are essential for human health, diets with a high ratio of omega-6 fatty acids to omega-3 fatty acids are often associated with cardiovascular disease, cancer and inflammatory and autoimmune diseases. A low ratio of omega-6 to omega-3 fatty acids, however, is believed to promote cardiovascular health, improve memory and, as the current study shows, protect bone health.

After 12 weeks, rats with the lowest ratio of omega-6 to omega-3 fatty acids in their diet experienced significantly less bone loss than rats in the other dietary groups.

"We saw in this study that omega-3 fatty acids are associated with a better blood profile of bone health, and with higher bone mineral density, in the absence of estrogen," Watkins said.

"A 5-to-1 dietary ratio of omega-6 to omega-3 fatty acids led to a conservation of bone mineral content that we didn't see with a 10-to-1 ratio," Watkins said.

While he cautions against translating these results to humans, Watkins does agree that omega-3s are an important part of a healthy diet.

"As a nation, we don't consume enough of these fats, but we're heading in the right direction," he said.

The average American dietary ratio of omega-6 to omega-3 fatty acids is approximately 10 to 1, a ratio inflated by the types of foods people eat and the methods used to produce those foods, especially those containing vegetable oils, Watkins said.

"Our foods are different today than they were yesterday," he said.

"Omega-6 fatty acids have been an important part of our diet, but over the past 80 years, the human diet has shifted in a way that increased the ratio of omega-6 to omega-3 fatty acids. In the past century, we've relied on high omega-6 grains like corn to feed livestock."

Animals such as cattle naturally feed on pasture grasses, which have a lower omega-6 to omega-3 ratio than grains like corn, Watkins said.

The omega-6 fatty acids in today's animal feed incorporate right into the animals' tissues where they become part of the eggs, poultry, meats and pork served in households and restaurants across the country.

"The expression 'you are what you eat' is truer than you think," Watkins said.

Seifert suggests the bone-protective effects of omega-3 fatty acids may be linked to their previously established role in minimizing inflammation in the body.

"We believe omega-3s may minimize bone loss with estrogen deficiency in association with their anti-inflammatory effects," he said.

Inflammation is caused by a number of compounds, including a class of molecules called cytokines. These compounds also stimulate bone breakdown, a natural part of a body process known as the bone cycle.

"Many people don't realize it, but our bones are not static structures," Seifert said.

Bones undergo a process called "remodeling," in which they are continuously broken down and rebuilt. Two types of cells found in bones govern this process - bone resorption cells, which remove small portions of bone, and bone building cells, which fill in the gaps.

Estrogen blocks some of the inflammatory compounds associated with bone resorption, which may explain why osteoporosis typically progresses after estrogen levels fall with the onset of menopause.

Likewise, Watkins' previous studies have shown omega-3 fatty acids may reduce the production of these same inflammatory compounds, accounting for their bone-protective effect.

"Omega-3s change the behavior of cytokines in a way that is consistent with the role of omega-3s in mitigating cardiovascular disease," Watkins said.

Watkins and Seifert have spent the last 10 years investigating the role of lipids on the biology of bone. "We began to question years ago how lipids may affect bones," Watkins said. "Our studies have laid the groundwork for other researchers today who have started to look for lipid effects on bone health in humans."

Yong Li, with the Purdue Center for Enhancing Foods to Protect Health, also participated in this research. The Indiana 21st Century Research and Technology Fund provided funding.

Writer: Jennifer Cutraro, (765) 496-2050, jcutraro@purdue.edu

Sources: Bruce Watkins, (765) 494-5802, baw@purdue.edu

Mark Seifert, (317)274-3353, mseifert@iupui.edu

Ag Communications: (765) 494-2722;
Beth Forbes, forbes@purdue.edu
Agriculture News Page



Dietary ratio of n-6/n-3 PUFA and docosahexaenoic serum biomarkers in the ovariectomized rat

Bruce A. Watkins,Yong Li, and Mark F. Seifert

Hypoestrogenic states escalate bone loss in animals and humans. This study evaluated the effects of the amount and ratio of dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on bone mineral in 3-month-old sexually mature ovariectomized (OVX) Sprague-Dawley rats. For 12 wks, rats were fed either a high PUFA (HP) or low PUFA (LP) diet with a ratio of n-6/n-3 PUFA of 5:1 (HP5 and LP5) or 10:1 (HP10 and LP10). All diets (modified AIN-93G) provided 110.4 g/kg of fat from safflower oil and/or high-oleate safflower oil blended with n-3 PUFA (DHASCO oil) as a source of docosahexaenoic acid (DHA). Fatty acid analyses confirmed that dietary ratio of 5:1 significantly elevated the amount of DHA in the periosteum, marrow, and cortical and trabecular bone of the femur. Dual energy x-ray absorptiometry (DXA) measurements for femur and tibia bone mineral content (BMC) and bone mineral density (BMD) showed that the DHA rich diets (HP5 and LP5) resulted in a significantly lower bone loss among the OVX rats at 12 wks. Rats fed the LP diets displayed the lowest overall serum concentrations of the bone resorption biomarkers pyridinoline (Pyd) and deoxypyridinoline, while the bone formation marker osteocalcin was lowest in the HP groups. Regardless of the dietary PUFA content, DHA in the 5:1 diets (HP5 and LP5) preserved rat femur BMC in the absence of estrogen. This study indicates that the dietary ratio of n-6/n-3 PUFA (LP5 and HP5) and bone tissue concentration of total long chain n-3 PUFA (DHA) minimize femur bone loss as evidenced by a higher BMC in OVX rats. These findings showed that dietary DHA lowers the ratio of 18:2n-6 (LA)/n-3 in bone compartments and that this ratio in tissue correlates with reduced Pyd, but higher bone alkaline phosphatase activity and BMC values that favors bone conservation in the OVX rat.



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