This Recently Discovered, Fascinating Brain-Bone Connection Will Amaze You - Save Our Bones

Today we’re going to delve into a fascinating way in which your brain and bones are connected. It involves a neurochemical known as neuropeptide Y, or NPY, which acts as an appetite stimulant and research has recently revealed that it has the capacity to reduce bone density.

In today’s post, we’re going to take a close look at this neuropeptide and its fascinating connective role between your brain and bones, and how levels of this neurochemical can be naturally regulated in the body.

What Is A Neuropeptide?

Communication between cells is crucial for any body system to function properly, and your nervous system is no exception. For intercellular communication to take place, neuropeptides are essential. They are short-chain polypeptides that act as neurotransmitters.

Unlike other neurotransmitters, neuropeptides appear to be associated with specific behaviors, such as maternal bonding. Oxytocin, for example, is a relatively well-known neuropeptide that influences social bonding behaviors.

Neuropeptide Y, or NPY, is less well-known, but is being linked to specific body processes. It’s related to peptide hormones and the hypothalamus, a complex area of the brain whose function is similar to a central processor that connects the nervous and endocrine systems.

Recent research has linked NPY to energy levels and body weight, and has revealed its role in bone density.

Neuropeptide Y – What It Is And What It Does

In 1982, NPY was isolated from the hypothalamus of pigs, and ever since then, scientists have speculated about its specific function(s). Over the years, research has revealed NPY’s role in obesity (it increases appetite), stress, and the growth and storage of fat in the body.1

A 1995 study found that chronically high levels NPY are associated with obesity in rats2, and it’s becoming increasingly clear that NPY works as a connective factor between the appetite hormones ghrelin and leptin to influence appetite, body weight, and bone density.

Study Reveals Connection Between Body Weight, Bone Density, And NPY

A 2009 study on knockout mice showed a remarkable interplay between obesity, fasting, and bone density. (Knockout mice are mice that have had a particular gene deactivated, or “knocked out” by artificial means.) In this particular study, mice that lacked NPY showed “significantly increased bone mass.”3

In contrast, the knockout mice, whose NPY levels were artificially increased, showed “a significant reduction in bone mass despite developing an obese phenotype.”3

This directly counters the myth that being overweight is good for bone density, as the scientists point out:

“Given the strong and positive association between increases in body weight and bone mass, in part due to mechanical effects of weight bearing, it is notable that tibial BMC was reduced by 19% (p<0.05) in WT [wild type] NPY+ mice compared to WT empty controls over the 4-week period, with no change in tibial BMD.”3

More importantly, the data show that reduced NPY levels enhance the activity of osteoblasts, the bone-building cells. As you’ll discover next, there are other mechanisms at work, too.

How Does A Lack Of NPY Increase Bone Density?

Researchers observed a “2-fold increase in bone formation rate” in the knockout mice compared to wild type mice, “demonstrating that NPY preferentially controls the anabolic aspects of bone homeostasis.”3 The question is, how?

NPY – specifically, a lack of it – appears to influence bone remodeling in two key ways. First, NPY is expressed via the hypothalamus, stimulating signals that regulate bone density “in a manner consistent with the central perception of energy status.”3

Second, NPY is expressed in osteoblasts, thus supporting the idea that NPY directly regulates osteoblast function. The less NPY is expressed, the greater the bone formation and subsequent density.

The researchers state that:

“In conclusion, these data identifies [sic] NPY as a critical integrator of bone homeostatic signals.”3

It’s noteworthy that the hypothalamic expression of NPY is increased during fasting, which is another reason why the Osteoporosis Reversal Program does not advocate skipping meals or other forms of fasting and food deprivation. Simply put, fasting contributes to low bone density.

Another reason that fasting is not recommended is that the practice tends to induce sugar cravings. As Savers are surely aware, too much sugar damages bones due to its inflammatory, acidifying nature and its role in Advanced Glycation End Products or AGEs formation. AGEs are inflammatory compounds formed when sugar molecules attach to proteins in the blood, and they can cause damage to tissues and organs, including bones. The more sugar that’s present, the more AGEs that form.

Additionally, NPY was shown to increase during times of stress, further proving that stress management is crucial to bone health. And a study shows that eating plenty of soluble fibre lowers NPY levels.4

The Osteoporosis Reversal Program Is Not About Deprivation

In sharp contrast to the Medical Establishment’s osteoporosis treatment, the Program centers around food – foods that provide bone-building Foundation Supplements, bone-smart antioxidants, decrease inflammation, and so much more. In a way, the Osteoporosis Reversal Program celebrates food and all it has to offer our bones and overall health.

A companion cookbook is the perfect complement to the Program, which is why I created Bone Appétit. Its full-color photos and over 200 creative recipes are in keeping with the celebratory spirit of eating to rejuvenate and build your bones.

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The Program’s nutritional plan is all about what you can eat, not what you can’t, and Bone Appétit develops this concept into a fun and varied nutritional plan chock-full of Foundation Foods that nourish your bones.

Bone Appétit shows you how eating your way to better bone health can be enjoyable and creative!

Till next time,


1 Kuo, Lydia E., et al. “Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome.” Nature Medicine. 13. (2007): 803-811. Web. June 22, 2016.
2 Dryden, Simon, et al. “Increased neuropeptide Y secretion in the hypothalamic paraventricular nucleus of obese (fa/fa) Zucker rats.” 690. 2. (1995): 185-188. Web. June 22, 2016.
3 Baldock, Paul A., et al. “Neuropeptide Y Knockout Mice Reveal a Central Role of NPY in the Coordination of Bone Mass to Body Weight.” PlosOne. (2009). Web. June 22, 2016.
4 Holzer, Peter, et al. “Neuropeptides and the Microbiota Gut-Brain Axis.” Adv Exp Med Biol. 2015 Mar 15.

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Comments on this article are closed.

  1. carmen benard

    please comment on the effect of bio identical progesterone on bone density as per dr. John Lee

  2. Alfonso

    How many hours of fasting begin the NPY expressed, , with daily ritmus, it is more than 13 hours.. Thanks

  3. Juanita Greenway

    How do I decrease NPY?

  4. shula

    This is a fascinating article; regarding craving sugar when fasting – not sure about this.

    • live4ever

      Blood sugar drops when fasting, expeditiously fasts. The up and down levels can disturb your metabolism making body crave that sugar lift. I try never to allow to get too hungry, Body,brain need steady supply of fuel.

  5. Jean

    Dear Vivian,
    thanks for all your information. I recently had a dexa scan and was delighted that my readings for the spine have improved however when I went to my dr. to discuss it she told me that I may have arthritis in my spine and that accounted for the good news that if you have arthritis in your system your dexa scan will show improvement in the results, what are your views on this subject.

    • Quebec City

      That is true, there may be bone spurs protruding to compensate for the misalignment of vertebrae, that may or may not be painful. This is happening to me. I have scoliosis and the strain on some areas of the vertebrae is stronger in some parts, hence increase in bone density.
      Blood tests for markers of bone formation are giving a whole picture. What to conclude if some bones are loosing density whereas some others are gaining density?
      In the first year I increased density by about ten percent in the spine and hips. Yet in the following 4 years, I lost most of the hip density while retaining the spine density I had gain, but this was due to bone compensating for malformation.
      A whole body approach is excellent in this view. But as yet except for a bone biopsy there is no test to measure real bone strength.

  6. Tom

    Another case of reductionism. Now we get to worry if we get enough — or even too much NPY. The overwhelming weight of the evidence says forget about individual nutrients and feast on a whole food Plant based diet eating all u want. And stay away from animal foods, medicines, drinks, etc that impair bone health.

    • Vivian Goldschmidt, MA

      Your individual NPY levels should cause you no worry, Tom. 🙂 Your point is right on – a whole foods, plant-based diet low in animal products is the best for restoring balance and promoting optimal health. Some of the mechanisms by which such a diet does so is often topic of posts like this one, and I know the community finds such information fascinating…as do I!

      • live4ever

        I like knowing how things work. New details help me stay with the right diet. We all know the diet. What I need is reminders thru new info to stay on track!! Thanks Vivian

  7. R. Lalitha

    How does migaine affect the production or non-production of NPY?

  8. Hilary Mitchell

    How do I increase the NPY?

  9. Michal

    How does Menopause affect the production or non production of NPY?

    • Vivian Goldschmidt, MA

      Hi Michal,

      Some interesting research is being done on the connection between the hypothalamus and menopause. A study from 2009 notes the following:

      “Reciprocal changes in neuropeptide Y (NPY) and proopiomelanocortin (POMC) gene expression occurs within separate subgroups of neurons in the hypothalamus of older women. Specifically, the number of neurons expressing POMC gene transcripts decreases in the infundibular nucleus of postmenopausal women whereas the gene expression of NPY neurons increases in both the infundibular nucleus and retrochiasmatic region. However, unlike the NKB and ERα mRNA expressing neurons in the infundibular nucleus, NPY and POMC neurons do not exhibit changes in cell size. Furthermore, the changes in NPY and POMC gene expression in postmenopausal women are not mimicked by ovariectomy of young cynomolgus monkeys. Thus, not all of the changes in gene expression observed within the hypothalamus of older women can be explained by ovarian failure.”

      You can read the rest of the study here:

  10. Maartje

    how do I increase the NPY?

    • Vivian Goldschmidt, MA

      Hi Maartje,

      NPY is increased by fasting, but increasing NPY has a negative effect on bone density, as noted in the post.

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