Can Manipulation of the Ratios of Essential Fatty Acids Slow the Rapid Rate of Postmenopausal Bone Loss?


Can Manipulation of the Ratios of Essential Fatty Acids Slow the Rapid Rate of Postmenopausal Bone Loss?

Debra B. Kettler, MS, DC

The rapid rate of postmenopausal bone loss is mediated by the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor alpha. Dietary supplementation with fish oil, flaxseeds, and flaxseed oil in animals and healthy humans significantly reduces cytokine production while concomitantly increasing calcium absorption, bone calcium, and bone density. Possibilities may exist for the therapeutic use of the omega-3 fatty acids, as supplements or in the diet, to blunt the increase of the inflammatory bone resorbing cytokines produced in the early postmenopausal years, in order to slow the rapid rate of postmenopausal bone loss. Evidence also points to the possible benefit of gamma-linolenic acid in preserving bone density.

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The National Institutes of Health Consensus Development Conference Statement on Osteoporosis Prevention, Diagnosis and Therapy, published in March 2000 states:

“Osteoporosis, once thought to be a natural part of aging among women, is no longer considered age or gender-dependent. It is largely preventable due to the remarkable progress in the scientific understanding of its causes, diagnosis and treatment. Optimization of bone health is a process that must occur throughout the lifespan in both males and females. Factors that influence bone health at all ages are essential to prevent osteoporosis and its devastating consequences.” [1]

In the United States today, eight million women have osteoporosis and 15 million more have osteopenia, placing them at increased risk for osteoporosis. One out of two women will have an osteoporosis-related fracture in their lifetime. Osteoporosis is responsible for more than 1.5 million fractures annually, with an associated cost for direct expenditures in 1995 (hospitals and nursing homes) of $13.8 billion. [2] The most typical sites of osteoporosis related fractures are the thoracic and lumbar vertebral bodies (T8 through L3), the proximal femur, distal radius, humerus, pelvis, and ribs. Of all osteoporotic fractures, those at the hip are associated with the highest risk of morbidity and mortality. [3]

Many factors contribute to the lifetime accumulation or decline in bone mineral density (BMD), including levels of the nutrients vitamin D, calcium, sodium, and protein, as well as lifestyle factors such as body mass index, exercise, drug and alcohol use, and smoking. [1,2] Remodeling of bone takes place throughout adult life, with osteoclasts resorbing old bone and osteoblasts creating new bone. These cells continuously renew the skeleton while maintaining its strength and density. Normally, in the adult skeleton, three percent of cortical bone and 25 percent of trabecular bone is remodeled each year. The primary characteristic of osteoporosis is a reduction in bone mass due to an increase in bone resorption over bone formation. Postmenopausal osteoporosis is characterized by an accelerated loss of bone tissue (2-4% per year on average) that begins after natural or surgical menopause, and lasts 5-10 years in the absence of treatment. Fractures are most likely to occur within 15-20 years after ovarian function ends. [4]

Postmenopausal bone loss is associated with an increase in both the number and activity of osteoclasts in trabecular bone. This rapid decline in BMD at menopause is often followed by a gradual decline in BMD, known as age-related osteoporosis (1-2% per year on average), which may persist indefinitely and may accelerate once more after the age of 70. [5] The rapid decline in BMD at menopause is the major factor contributing to the high rate of disabling bone fractures in postmenopausal women. [6]

Review of Fatty Acids

There are two classes of essential fatty acids (EFAs): omega-3 and omega-6. Humans (like all mammals) are unable to synthesize EFAs so they must be provided in the diet. [17] EFAs are required for membrane integrity, visual and neurological function, and their deficiency is associated with neurological and immunological disease. [18] Small changes in the fatty acid composition of the cell membrane can significantly alter cell function. [19]

The parent compound in the omega-6 fatty acid family is linoleic acid (LA), while the parent compound of the omega-3 fatty acid family is a-linolenic acid (ALA). These parent compounds are metabolized to longer-chain fatty acids (which play other, more important roles in the body) by a series of elongation and desaturation steps (Figure 3). LA is first converted to gamma-linolenic acid (GLA), then to dihomogamma-linolenic acid (DGLA) and arachidonic acid (AA), while ALA is converted to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). [19]

Although the omega-3 and omega-6 fatty acids compete for the desaturation enzymes, the D 4 and D 6 desaturases favor the omega-3 fatty acids. [17] Generally, the desaturation steps are slow and rate limiting, while the elongation steps usually proceed rapidly. Factors known to inhibit fatty acid desaturation are aging, smoking, diabetes, high sodium intake, and biotin deficiency, whereas calcium deficiency can impair essential fatty acid elongation. [19]

Fatty fish are the major source of EPA and DHA in the U.S. diet, while vegetable oils, especially soybean and canola oils, are the primary sources of ALA. Although flaxseed oil contains approximately 57-percent ALA, it is not commonly used in food preparation. Nuts, seeds, vegetables, and some fruit, as well as egg yolk, poultry, and meat contribute small amounts of omega-3 fatty acids to the diet.

The typical American diet has a high ratio of omega-6:omega-3 fatty acids. [20] Studies show that the consumption of increased amounts of fish, [21] fish oil, [22-25] flaxseed oil, [25,26] or canola oil [27] will result in the incorporation of the longer-chain omega-3 fatty acids EPA and DHA into the plasma and cell membranes of platelets, erythrocytes, neutrophils, monocytes, and liver cells. This leads to a change in the ratio of omega-6:omega-3 fatty acids in the membranes, [28,29] a change in the function of the membranes, [29] and a decrease in the production of IL-1, IL-6 and TNFa. [22-25]


Although low peak bone mass contributes to postmenopausal osteoporosis, an ovarian hormone-dependent increase in bone remodeling and accelerated loss of bone in the early years postmenopause appear to be the main pathologic factors. The NIH Consensus Statement calls for HRT and consumption of recommended dietary intake levels of calcium and vitamin D as the most effective way to build bone mass at menopause. [1] However, a proper balance of the essential fatty acids, without the inclusion of HRT, may also play a role in minimizing bone loss at menopause. [30-33, 42] Most women are very concerned with menopausal weight gain and may diet extensively to control their weight. A study by Salamone et al [43] demonstrated that this could have deleterious effects on BMD, as the intervention group of perimenopausal women (average age 46.7 ± 1.7 years), who modified their lifestyle to lose weight by lowering fat intake and increasing physical activity, had a two-fold greater rate of loss in hip BMD (p=0.015) compared to a non-dieting control group. The loss of BMD with dieting may be induced by alterations in the total body content of the essential fatty acids, such as by membrane depletion or preferential utilization and excretion. [44]

None of the studies reviewed can definitively conclude that increasing the level of omega-3 fatty acids or manipulating the ratio of GLA:EPA in the diet will slow the rapid loss of bone at menopause. However, there are interesting associations that deserve further attention. Inflammatory cytokines are produced in the local bone environment at menopause, [13-15] and monocytes are the primary producers of IL-1 and TNFa in the local bone environment. [5] Supplementation of omega-3 fatty acids as fish oil, dietary fish, and flaxseed oil decreases the production of IL-1, IL-6, and TNFa in cultured PBMCs. [22-25] The fatty acids GLA, EPA, and DHA in plasma and cell membranes are positively correlated to bone calcium. [32]

Incorporating higher amounts of the omega-3 fatty acids into the diet, thereby altering the ratio of omega-6:omega-3, while concurrently increasing vitamin E intake to inhibit lipid peroxidation, may have a positive effect on calcium absorption and bone density. There is also a need for additional study to further understand the relationships between fatty acids, calcium, and vitamin D. Such studies could supplement different ratios of the parent fatty acids LA:ALA, different ratios of GLA:EPA+DHA, or different ratios of GLA:ALA, while controlling for current LA:ALA levels in the diet, saturated and monounsaturated fat, vitamin D and calcium intake, and measuring BMD, Dpyd, serum 25(OH)D, and PTH in pre- and postmenopausal women.