Thursday, February 21, 2013

New Finding Shows that Nitrates May Help Reduce Both Spine and Hip Fractures

This morning, as I sipped my delicious nitrate-rich homemade beetroot juice (recipe below), I read with delight the International Bone and Mineral Society’s BoneKey Report about new evidence that nitric oxide may hold true promise in the fight against osteoporosis. Researchers Celeste Hamilton and colleagues from the University of Toronto examined important evidence that supports the concept that nitric oxide (NO), the smallest signaling molecule in the body, is not only critical for bone cell function and maintaining balance in the bone remodeling process, but may hold a key role in the treatment of osteoporosis. Great endorsement for the way I start my day!

During bone remodeling, a biological process that is constantly under way in the body, old weakened bone is broken down, or resorbed, and then new bone is formed it its place. Remodeling has to stay in balance for bone to remain healthy and strong. If bone remodeling becomes unbalanced and osteoclast bone resorption becomes overly aggressive, and/or osteoblast bone formation is impaired, this sets the stage for osteoporosis. It is through a complex set of signaling molecules that bone cells communicate with each other and maintain this balance. Nitric oxide (NO) is one of those molecules that bone cells use to “talk” to each other during the bone remodeling process. When NO production dwindles, as is the case during menopause when estrogen levels recede, osteoclast bone resorption increases. When NO production increases, this sets off a chain reaction of events that lowers osteoclast bone resorbing activity.  In other words, if you have osteoporosis, increasing NO levels in the body can be of great benefit.

According to Hamilton et al., organic nitrates* such as nitroglycerin can be used on an intermittent bases to increase NO levels. The researchers found that the higher NO levels improved bone cell function and substantially increased bone mass (not just density) both in trabecular and cortical bone! What this means is that nitrates may help reduce both spine and hip fractures. Bisphosphonate medications, the current drugs of choice for treating osteoporosis, are helpful for reducing vertebral fractures but have limited benefit in the war against hip fractures.

Unfortunately, there are two major drawbacks for using organic nitrates to treat osteoporosis. First, when used continuously organic nitrates could actually be detrimental; second, they have the nasty side effect of severe headaches. There are also economic considerations. Organic nitrates are typically very inexpensive to produce and because they have been around since the early 1800’s, obtaining patents can be difficult. This is an unattractive combination for pharmaceutical industries.

The good news is there are foods with inorganic nitrates and supplements that promote nitric oxide naturally. There are two biological pathways that produce NO:

1.     Arginine supplements    L-arginine + oxygen  + cofactors  ➜  nitric oxide synthase  ➜  NO
Nitric oxide is generated by a specific enzyme (NOS) from the amino acid arginine. For years
arginine (or citrulline which can also increase arginine and NO levels) has been used by athletes
to improve physical performance (NO enhances muscle tone and endurance) and by nutrition
experts to lower blood pressure (NO is a potent vasodialator). The problem with taking
supplemental arginine is that for the body to convert it into NO requires (1) plenty of oxygen
(not always that plentiful in osteoporotic bone), (2) several important cofactors (some of which
may be reduced especially in cases of mitochondrial dysfunction and arterial disease, common
in folks with osteoporosis), and (3) a functioning NOS enzyme system (which unfortunately
is not always present due to genetic polymorphisms).

2.      Nitrate-rich foods         nitrate  (NO3)  +  (oral bacteria)  ➜   nitrite  (NO2)  ➜    NO
Vegetables, especially leafy greens, are excellent sources of nitrate but beetroot is at the top
of the list. Beetroot juice is not only rich in vitamin C, B vitamins, folate, potassium, silica and
iron but it is your best source of nitrate. Studies show beetroot juice can significantly raise
blood nitrate levels, reduce blood pressure, and improve aerobic fitness through what has
been surmised as its ability to increase NO levels in the body. Beetroot is known for its
beneficial effects to bone due to its potassium, magnesium, manganese and silica but now
we may be seeing the best reason yet for adding beetroot juice to your armamentarium
against bone loss. And (as if it couldn't get better), if you are one of those individuals with 
elevated homocysteine levels, beetroot is a rich source of the phytonutrient, glycine betaine.
Homocysteine is an inflammation biomarker commonly seen elevated in people with
osteoporosis. Blood levels above 8 micromoles/L are indicative of inflammation, and when
they rise above 15, there is a 2.5-fold increase in fracture risk. (For more on inflammatory
biomarkers and how to lower them, see my book The Whole-Body Approach to Osteoporosis.)

The clear choice for most of us is nitrate-rich foods. I often start my day with a homemade beetroot juice mix. You can purchase beetroot juice but I like it fresh and organic. You’ll need a juicer but it is well worth it. Here is one of my favorite recipes:

2 beetroots (not the green tops)
2 apples
3 large carrots and 4 stalks of celery
½ bulb fennel
5 leaves of kale (can be difficult to juice )
large handful of parsley

Note: Make sure you sip and enjoy your juice. The bacteria that naturally live in your mouth are a necessary part of converting nitrates into nitrite, a necessary step before your body can then make it into NO.


* Organic nitrates are drugs such as nitroglycerine and inorganic nitrates are from dietary sources such as beetroot and green leafy vegetables.


Hamilton CJ, et al. 2013. Organic nitrates for osteoporosis: an update. BoneKey Reports doi:10.1038/bonekey.2012.259.
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