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January 8, 2019


by Nicola Schuler, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

In Part 2, we covered the gut as a root cause, the triggers and risk factors for FM. Now in Part 3, we will cover the specific action steps to take if you have FM. We first take a look at the various dietary issues that play a role in FM, starting with excitotoxins. A general anti-inflammatory diet is a great place to start, and then it would be beneficial to trial some of these other dietary ideas, along with finding a good Functional Medicine practitioner to help work through the possible root causes of your FM.

What is the role of excitotoxins?

Excitotoxins are molecules, such as glutamate and aspartate, which are involved in pain occurrence (10). They are excitatory neurotransmitters, whose role is to maintain and extend action potentials, which are electrical signals, in the brain. This is how brain cells communicate with each other. When these neuron receptors are exposed to excitotoxins, they fire impulses at such a rapid rate that they become exhausted, damaged or die. This is excitotoxicity.

Through a chemical process in the brain, the excitatory amino acid glutamate can cause chronic pain (10). In addition to glutamate’s role in central sensitization of pain, abnormal glutamatergic neurotransmission has also been implicated in other common pain conditions such as migraine, TMJ disorder, IBS and depression (10). Furthermore, substance P is a compound in the brain thought to be involved in the transmission of pain and other nerve impulses. It is co-released with glutamate and increases the permeability of the blood brain barrier (BBB) (10). If this barrier becomes permeable, then more glutamate can enter the brain and have further influence on the sensation of pain in FM.

In the diet, glutamate and aspartate are found in foods such as MSG, hydrolyzed protein, protein isolates/concentrates, yeast extract, aspartame, as well as in specific food items such as soy sauce, fish sauces and aged cheeses like sharp cheddar and parmesan cheese. People who eat more of these foods, or who are more sensitive to excitotoxins, could have higher blood concentrations which could lead to abnormal central sensitization of pain, which could be negatively compounded in people with an impaired BBB (10).

One study looked at 4 patients and found that all 4 had complete, or nearly complete, resolution of their symptoms within months after eliminating MSG plus aspartame from their diet (11). Further studies have shown a decrease in FM symptoms after the removal of excitotoxins (10).

It is certainly worth trialing a diet free of excitotoxins to see how it may help FM symptoms as dietary excitotoxins may be leading to increased symptoms in FM. This would involve focusing on a whole foods diet and removing MSG, aspartame and altered proteins (like gelatin, hydrolyzed protein, autolyzed yeast extract, protein concentrates and protein isolates). Certain ingredients on food labels like spices, seasoning, flavoring and natural flavoring should also be avoided since these terms are not specific and could hide these additives. Seasoning packets commonly contain flavor enhancers like MSG.  Additionally, foods naturally high in free glutamate including soy sauce, fish sauces, Worcestershire sauce, Bragg’s amino acids and cheeses like parmesan should also be avoided. To avoid aspartame, it is important to avoid diet soda, gum and breath mints. Yogurt, cereal and bread often have aspartame added. 

A 1-month testing period (without eating out) is ideal, though in prior research most subjects started to feel an improvement by the end of the first week (10).

Are micronutrient deficiencies involved?

Another dietary avenue found in research involves correcting particular micronutrient deficiencies. Micronutrients play an important role in optimal neuronal function, and a few nutrients in particular may relate to glutamatergic neurotransmission (10).

  • Magnesium and zinc are two minerals in the diet with a key role in regulating excitotoxicity. It is thought that low magnesium and zinc levels could support excitotoxicity (10).
  • Another micronutrient of importance to glutamatergic neurotransmission is vitamin B6. Deficiency in B6 can lead to higher levels of glutamate which would enhance excitotoxicity in the central nervous system (10).
  • Deficiency in omega-3 fatty acids has been shown to increase excitotoxicity (10). Omega-3 fatty acids to can potentially clear excess glutamate and prevent excitotoxicity.
  • Finally, excessive glutamatergic neurotransmission leads to increased need for antioxidants in the diet (10). The two main vitamin antioxidants in the diet are vitamin C and vitamin E.

What about supporting serotonin?

Another study focused on relieving FM symptoms through supporting serotonin synthesis through proper absorption of tryptophan in food, while avoiding food components such as fructose and sorbitol that may interfere with the absorption of tryptophan (12). The study was done on 1 FM patient. Encouragingly, this diet resulted in a rapid improvement of symptoms after only few days on the diet, up to the remission of most symptoms in 2 months (12). The patient periodically challenged herself by breaking the diet which resulted in a recurrence of the symptoms.

The patient’s diet included eggs, meat, fish, clams, potatoes, carrots, celery, spinaches, beets, chards, dark chocolates (at least 70 + % cacao), rice, millet, carob powder, walnuts, extra virgin oil, grape seed oil, thyme, sage, rosemary, coffee, green tea, and small amount of almonds. Foods that were avoided were processed food containing artificial sweeteners, high fructose corn syrup, sorbitol, glutamate, and aspartame such as soft drinks, fruit juices and confectionery, any food containing free fructose such as honey and fruits, most legumes, wheat and cereals, and many vegetables that contain fructans and inulins (12). Whilst very encouraging, this study involves one person so it is unclear how applicable it may be to other FM sufferers.

Also, natural supplements can help. We like 5-HTP for serotonin support. 50-100mg per day is a good place to start. If there are sleep issues, taking it before bed can help improve melatonin status because after 5-HTP converts to serotonin, it then converts to melatonin.

What about raw food?

A small study involving 30 patients was done trialling a mostly raw, pure vegetarian diet (13). Participants ate raw fruits, salads, carrot juice, tubers, grain products, nuts, seeds, and a dehydrated barley grass juice product. 19 of the 30 participants experienced significant improvement in all symptoms (13). At 7 months, these people were no longer statistically different from norms for women ages 45–54, apart from the symptom of bodily pain (13). This was the symptom that responded least well to the raw diet.

What about going gluten-free?

One study looked at people suffering from FM, as well as IBS. Amongst their study sample, 7 were women who also had (previously undiagnosed) celiac disease. After 1 year on a gluten-free diet, these participants experienced significant improvement in FM symptoms. The authors of the study believe that this indicates an underlying food hypersensitivity-related mechanism (14).


Would healing the gut help?

If a gluten-free diet can lead to significant improvement in symptoms and we know that there may be a connection between FM and gut conditions like IBS, SIBO, dyspepsia, leaky gut, celiac disease and possibly others, then we can surmise that healing the gut will help in the case of FM. We could take that one step further and embark on a specific and targeted gut healing protocol, which would focus on healing the specific gut condition, be it IBS, SIBO, celiac, etc., in order to alleviate FM symptoms.


Although conventional medicine has focused on managing symptoms of FM, there are a number of dietary treatment ideas that can lead to a complete or partial improvement in FM symptoms, according to the studies that exist.

Gut healing is an obvious place to start with the possibility of also focusing on excitotoxins, micronutrient levels and/ or serotonin support.

Things that you can do for FM:

  • Find a functional medicine doctor to do root cause lab testing (call us at 720-722-1143 if you want to find out more about how to set up an appointment in our office)
  • Get functional lab tests to identify root causes (a list of these are included below)
  • Dietary change (trial different diets and include elimination of excitotoxins, removal or minimization of gluten and sugar, and increase micronutrients discussed in this article)
  • Support serotonin through diet and/or take 5-HTP 50-100mg daily (before bed if you have sleep issues) – you can order through our online supplement store here:
  • Some of the micronutrients that could be supplemented (and/or you can get them from diet) include: Vitamin B6 (P-5-P 50mg per day), Zinc (15-30mg daily), Omega 3 (Cod Liver Oil or other quality fish oil), Vitamin C (600-1200mg per day), Vitamin E (we don’t like alpha tocopherol, but Annatto Tocotrienols that are high Gamma can help at about 125mg daily with dinner).
  • Magnesium is often helpful for FM: Magnesium Glycinate 400-600mg per day
  • If you’d like a supplement pack auto-shipped to you monthly with a specially formulated combination including the above plus some other supplements we have found helpful, email with the subject line “Fibromyalgia Supplement Packs” to find out more information about how to get started.

Labs to find root causes associated with FM:

  • Small Intestinal Bacterial Overgrowth (SIBO) breath test
  • Comprehensive Data Stool Analysis (CDS) with Parasitology x3
  • HLA-DR panel for genetics associated with mold toxin accumulation
  • Blood sugar panel including fasting glucose, HgA1c, and fasting insulin
  • Blood hormone panel including Estradiol, Progesterone, Testosterone, Cortisol, and DHEA-S (for menstruating women not on a hormonal birth control, getting this on days 18-22 is best)
  • Toxic metals panel
  • Organic Acids panel
  • NOTE: not all of these labs are needed for everyone with FM. A skilled functional medicine doctor can prioritize which are most necessary based on a comprehensive case history to assess for which root causes are more likely. The functional medicine doctor can then prioritize the most likely root causes and start testing just for some of the main issues that would be most likely. Follow-up testing can be done if findings are not as expected on the initial lab order. If you would like to find out more about getting started with a functional medicine doctor in our clinic, click on “Schedule a Discovery Call” now.


10. Holton The role of diet in the treatment of fibromyalgia. Pain Management. 2016; 6.

11. Smith JD, Terpening CM, Schmidt SO, Gums JG. Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. Ann Pharmacother. 2001; 35:702-6.

12. Lattanzio SM, Imbesi F. Fibromyalgia Syndrome: A Case Report on Controlled Remission of Symptoms by a Dietary Strategy. Front. Med. 2018 |

13. Donaldson MS, Speight N, Loomis Fibromyalgia syndrome improved using a mostly raw vegetarian diet: An observational study. BMC Complement Altern Med. 2001; 1: 7.

14. Rodrigo L, Blanco I, Bobes J, and de Serres Clinical impact of a gluten-free diet on health-related quality of life in seven fibromyalgia syndrome patients with associated celiac disease. BMC Gastroenterol. 2013; 13: 157.

15. Curtis K, Osadchuk A, Katz J. An eight-week yoga intervention is associated with improvements in pain, psychological functioning and mindfulness, and changes in cortisol levels in women with fibromyalgia. J Pain Res. 2011 ;4:189-201.

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December 7, 2018


by Nicola Schuler, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

In Part 1 of this 3-part series on FM, we looked at what FM is and what the root causes are thought to be, according to both the research and Functional Medicine. These include abnormalities in the central nervous system, genetic factors, psychological variables, and environmental factors (1). In Functional Medicine, we will also look at gut issues, toxic burden, chronic infections, insulin resistance and hormone and/or neurotransmitter imbalances.

Here, In Part 2 we cover the gut as a root cause, the triggers and risk factors for FM. We will also touch on the treatment of FM, which we will then explore in much greater depth in Part 3 of this series on FM.



Could FM be related to the gut?

One environmental (or epigenetic) factor that has been looked at is gut health. It is possible that gut health is a contributing cause of FM, although this has not yet been proven. However a number of studies have linked FM to gut dysbiosis, infections and other gut conditions. Many of the studies correlate FM with GI symptoms, Irritable Bowel Syndrome (IBS) and dyspepsia (7). Other studies have associated FM with Small Intestinal Bacterial Overgrowth (SIBO) and leaky gut (8). Finally one study found that FM symptoms improved in fibromyalgia patients who treated and resolved their SIBO condition with antibiotics. In this same study, no improvement was seen in the patients who took a placebo or who still tested positive for SIBO after the antibiotics. (7). This suggests that SIBO plays a causal role in fibromyalgia for at least some patients.

Although gut health is not a defined known cause of FM, we mention it here because it is a distinct possibility and there are indications that this may be an avenue for further research. It is also worth highlighting because improving gut health is something that everyone can work on, whether they have FM or not. If FM is in a person’s family history, then it may be even more relevant to work on gut health.

We suggest finding a good functional medicine doctor and testing for gut issues like SIBO (lactulose breath test) and other bacterial / parasite / fungal issues (comprehensive stool test).


What are the triggers of FM?

There is often a trigger of the onset of FM. It can be triggered by various factors such as:

  • stress and/or a major life event such as divorce or the death of a spouse
  • trauma, whether it is emotional, physical or in the form of an accident
  • an infection or virus of some sort
  • surgery
  • repeated injuries
  • childbirth


What are the risk factors for FM?

There are certain risk factors that contribute to the likelihood of developing fibromyalgia. These include:

  • Gender: 80-90% of patients with FM are women between 30 and 50 years of age (9). The reason for this isn’t known.
  • Family history: As mentioned above, a family history of the condition may increase the risk of developing FM
  • Disease: Although fibromyalgia isn’t a form of arthritis, having a rheumatic disease like lupus or rheumatoid arthritis or osteoarthritis may also increase risk.
  • Inflammation (from one or more of the causes we discussed and/or inflammation from poor diet)


How is FM diagnosed?

FM is difficult to diagnose. There is currently no available imaging technologies or analytical tests for an objective diagnosis (1). FM is now defined as chronic widespread pain, persisting for more than 3 months, without any obvious wound or lesion. FM is commonly accompanied by additional symptoms, as mentioned above, such as joint stiffness, fatigue, sleep disturbance, cognitive dysfunction, and depression. Diagnosis tends to be subjective based on the symptoms and how the patient describes them to their doctor. Diagnosis also includes ruling out other possible diseases such as Rheumatoid Arthritis, depression, Multiple Sclerosis or other autoimmune conditions. Although debate on the concept of FM has continued ever since the classification criteria for diagnosis were first published, FM is now better understood and is generally recognized as a disorder.


How is FM treated?

There is no clear-cut treatment plan for FM and no one treatment alone gives strong relief of symptoms. The current conventional medicine approaches seek to manage the condition and manage the pain. Conventional medicine typically uses analgesic medications (OTC pain relievers like ibuprofen, or prescription drugs like tramadol), antidepressants, and anti-seizure drugs (which are sometimes helpful in reducing certain types of pain).There are, however, a number of things that can be done that have shown promise or that have worked in specific studies. We will mention a few natural dietary approaches for which there is promising research.

Functional medicine doctors will look for root causes of inflammation and resolve those root issues. We have seen many people with FM have complete recovery in our clinic from working out inflammatory root causes.


What are specific treatment ideas for FM?

Diet is increasingly thought to be a factor in FM. There is growing evidence that diet may contribute to symptoms, with strong evidence for how specific foods may lead to abnormal neurotransmission and continue the process of central sensitization (of pain) (10).

In our clinic, we use a variety of dietary approaches that are specifically tailored to the root causes we find on lab testing. Unfortunately, there is not one diet that works best for everyone with FM. Many times we have patients do one diet for a period of time and then switch diets if we’re not getting results. We also are combining diet with specific supplement and herbal protocols all based on root cause. All this to say that we cannot give one diet that will work for everyone. What we can do is give some general principles that can be helpful guides to consider as part of your dietary plan.

Many with FM do well avoiding gluten and sometimes even all grains. Avoiding refined sugar is also often helpful. Some have success with Paleo diets, others do well with Autoimmune Paleo, others do well with Ketogenic diets, and still others do well with Mediterranean diets (usually gluten-free). There are a few more specifics that can be helpful that will be covered in the next sections.

Please stay with us and read Part 3 of our FM series. In Part 3 we will cover the specific dietary and other action steps to take if you have FM.



1. Park DJ, Lee SS. New insights into the genetics of fibromyalgia. Korean J Intern Med. 2017; 32:984-995.
2. Abeles AM, Pillinger MH, Solitar BM, Abeles M. Narrative Review: The Pathophysiology of Fibromyalgia. Ann Intern Med. 2007; 146:726-734.
3. Flodin P, Martinsen S, Löfgren M, Bileviciute-Ljungar I, Kosek E, Fransson P. Fibromyalgia is associated with decreased connectivity between pain- and sensorimotor brain areas. Brain Connect. 2014; 4:587-94.
4. Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol. 2004; 31:364-78.
5. Kwiatek R, Barnden L, Tedman R, Jarrett R, Chew J, Rowe C, et al. Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. Arthritis Rheum. 2000; 43:2823-33.
6. Mogil JS. Pain genetics: past, present and future. Trends Genet 2012; 28:258–266.
7. Wallace DJ, Hallegua DS. Fibromyalgia: the gastrointestinal link. Curr Pain Headache Rep. 2004; 8:364-8.
8. Goebel A, Buhner S, Schedel R, Lochs H, Sprotte G. Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome. Rheumatology (Oxford). 2008; 47:1223-7.
9. Carranza-Lira S, Villalobos Hernandez IB. Prevalence of fibromyalgia in premenopausal and postmenopausal women and its relation to climacteric symptoms. Prz Menopauzalny. 2014; 13: 169–173.
10. Holton K. The role of diet in the treatment of fibromyalgia. Pain Management. 2016; 6.
11. Smith JD, Terpening CM, Schmidt SO, Gums JG. Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. Ann Pharmacother. 2001; 35:702-6.
12. Lattanzio SM, Imbesi F. Fibromyalgia Syndrome: A Case Report on Controlled Remission of Symptoms by a Dietary Strategy. Front. Med. 2018 |
13. Donaldson MS, Speight N, Loomis S. Fibromyalgia syndrome improved using a mostly raw vegetarian diet: An observational study. BMC Complement Altern Med. 2001; 1: 7.
14. Rodrigo L, Blanco I, Bobes J, and de Serres FJ. Clinical impact of a gluten-free diet on health-related quality of life in seven fibromyalgia syndrome patients with associated celiac disease. BMC Gastroenterol. 2013; 13: 157.
15. Curtis K, Osadchuk A, Katz J. An eight-week yoga intervention is associated with improvements in pain, psychological functioning and mindfulness, and changes in cortisol levels in women with fibromyalgia. J Pain Res. 2011 ;4:189-201.

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November 7, 2018

Fibromyalgia | Blog Series Part 1

by Nicola Schuler, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

What is Fibromyalgia?

Fibromyalgia (or FM) is a neurological disorder of the central nervous system. It is a syndrome of chronic pain in the absence of an otherwise apparent disease or cause for the pain. Patients with FM experience pain differently than people without FM.


Primary symptoms associated with fibromyalgia:

• Widespread pain throughout the body
• Heightened and painful response to pressure resulting in exaggerated tenderness at specific points
• Debilitating exhaustion
• Joint stiffness
• Sleep Issues
• Unrefreshing sleep
• Cognitive decline (problems with brain fog, memory, concentration, etc.)

People with fibromyalgia (or FM) may also have depression or other psychological difficulties, headaches, and an inability to focus or concentrate. FM is only recently recognized as a disorder. It is considered a major health problem, which affects 1% to 5% of the general population (1). It is more common in women than men. Having FM can be challenging and in some cases can lead to a lower quality of life and high medical costs.

The condition is chronic. At this time, conventional medical treatment is focused on managing the condition and the associated pain. The cause or causes are not clear but fortunately significant advances have been made in understanding FM. Fortunately, functional medicine has some insights to offer for those suffering with FM.

What causes FM?

The precise cause of FM has not been identified at this time. Various factors can contribute to or trigger FM.
Currently, FM is considered to involve the interaction of several factors, including abnormalities in the central nervous system, genetic factors, psychological variables, and environmental factors (1).

It is thought that the symptom of pain in FM is related to central sensitization, which is an explanation for chronic pain of FM (2). Central sensitization refers to blunting of inhibitory pain pathways and alterations in neurotransmitter levels, leading to abnormal processing of sensory signals within the central nervous system, eventually lowering the threshold of pain and amplifying the sensations from normal signals, causing chronic pain (2). The details are not fully understood yet.

As the issue lies with the central processing of pain, we know that it is not in the peripheral body areas where FM patients experience the pain. The mechanisms thought to be involved include the central sensitization of pain, a suppression of the descending pathways that inhibit pain, excessive activity of glial cells, and abnormalities of neurotransmitter release or regulatory proteins or both (2). These mechanisms are probably not mutually exclusive.

In studies, FM patients show decreased connectivity between different parts of the brain. Findings suggest that abnormal connectivity patterns between pain-related regions and the remaining brain reflect an impaired central mechanism of pain modulation in FM (3). Weaker coupling between pain regions and other areas of the brain possibly indicate an inefficient control of pain circuits. The findings show that FM primarily is associated with decreased connectivity between regions of the brain, which could reflect a deficiency in pain regulation (3). Essentially the brain is overly sensitive to pain signals or misinterprets pain signals.

Unfortunately, these conventional understandings of the causes of FM leave a lot to be desired. There is not much that is actionable or straightforward in helping people struggling with FM to do something for themselves. Luckily, functional medicine has some strong links and connections with root causes that can be contributing to FM.

From a functional medicine perspective, inflammation is a key element when looking at most kinds of pain. FM pain is certainly one for which it is important to find root causes for inflammation and reverse them.

Functional Medicine Root Causes for FM:

• Gut issues (we will talk about that more in Part 2 of this article)
• Toxic Burden: mold toxin accumulation, toxic metals, and/or excessive chemical exposure
• Chronic Infections: Lyme disease, chronic bacterial or viral infections, or fungal / yeast overgrowths
• Insulin resistance: blood sugar and insulin issues can contribute to inflammation and pain
• Hormone and/or neurotransmitter imbalances

Finding a skilled functional medicine doctor familiar with these root causes can help to do some lab testing for HLA-DR genetics (associated with mold toxin accumulation), Lyme testing (find a Lyme-literate functional medicine doctor), gut testing like SIBO and comprehensive stool testing, comprehensive hormone blood panel, and a blood sugar panel that includes fasting glucose, HgA1c, and fasting insulin.

*NOTE: we DO NOT recommend urine-based neurotransmitter testing (however we do like urine testing for Organic Acids which can give a sense of neurotransmitter levels). It is not accurate in our opinion and research does not support this kind of testing. There are plasma neurotransmitter tests that are decent tests, but because of limitations in testing, we often use organic acids and/or a questionnaire and symptom picture to get a sense for neurotransmitter status.

Is FM genetic?

The other key factor believed to play a role in FM is genetics. There is an observed inherited component to FM. Studies have been conducted looking for family associations in FM and have found that anywhere from 26% to 52% of family members of a person diagnosed with FM also fit the criteria for a FM diagnosis (1).

Interestingly, the genetic aspect ties in with the issue of malfunctioning pain signaling. Researchers have identified pain-related genes and have found that pain-related genes affect the expression or function of specific proteins which influence the pain response (6). Currently, hundreds of pain-regulated genes related to pain perception or analgesia have been identified. These include the genes encoding voltage-gated sodium-channels (Nav), GTP cyclohydrolase 1 (GCH1), mu-opioid receptors, and catechol-O-methyl transferase (COMT); and various genes of the dopaminergic, glutamatergic, and GABAergic pathways (1).

However, we must keep in mind that genes are not destiny. Epigenetic, or environmental factors, affect how a particular gene or genes is expressed. Therefore, having these genes related to pain signaling is not a guarantee that fibromyalgia will follow. It is the genetic expression of these genes that is most relevant and this can be affected by epigenetic factors.

It is thought that hormone imbalances, particularly involving serotonin, dopamine and norepinephrine, can play a part in FM. Recent research has focused on how genes can trigger changes in gene expression in people with FM. Research has shown that genetic SNP’s, or genetic mutations of specific genes, result in an increased sensitivity to pain. These SNP’s are related to certain hormones which help to regulate pain. In fact, associations between FM and certain genetic mutations affecting the serotonergic, dopaminergic, and catecholaminergic pathways have been found (1). These mutations influence symptom severity as well as susceptibility to FM. However, the genetic factors identified to date do not fully explain the cause of FM (1). FM is considered to result from an interaction between genetic factors and environmental factors.

Please read on to Part 2 of this overview of FM. In Part 2 we cover the gut as a root cause, the triggers and risk factors for FM. Part 3 will cover the specific action steps to take if you have FM.



1. Park DJ, Lee SS. New insights into the genetics of fibromyalgia. Korean J Intern Med. 2017; 32:984-995.
2. Abeles AM, Pillinger MH, Solitar BM, Abeles M. Narrative Review: The Pathophysiology of Fibromyalgia. Ann Intern Med. 2007; 146:726-734.
3. Flodin P, Martinsen S, Löfgren M, Bileviciute-Ljungar I, Kosek E, Fransson P. Fibromyalgia is associated with decreased connectivity between pain- and sensorimotor brain areas. Brain Connect. 2014; 4:587-94.
4. Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH. Functional imaging of pain in patients with primary fibromyalgia. J Rheumatol. 2004; 31:364-78.
5. Kwiatek R, Barnden L, Tedman R, Jarrett R, Chew J, Rowe C, et al. Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. Arthritis Rheum. 2000; 43:2823-33.
6. Mogil JS. Pain genetics: past, present and future. Trends Genet 2012; 28:258–266.
7. Wallace DJ, Hallegua DS. Fibromyalgia: the gastrointestinal link. Curr Pain Headache Rep. 2004; 8:364-8.
8. Goebel A, Buhner S, Schedel R, Lochs H, Sprotte G. Altered intestinal permeability in patients with primary fibromyalgia and in patients with complex regional pain syndrome. Rheumatology (Oxford). 2008; 47:1223-7.
9. Carranza-Lira S, Villalobos Hernandez IB. Prevalence of fibromyalgia in premenopausal and postmenopausal women and its relation to climacteric symptoms. Prz Menopauzalny. 2014; 13: 169–173.
10. Holton K. The role of diet in the treatment of fibromyalgia. Pain Management. 2016; 6.
11. Smith JD, Terpening CM, Schmidt SO, Gums JG. Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. Ann Pharmacother. 2001; 35:702-6.
12. Lattanzio SM, Imbesi F. Fibromyalgia Syndrome: A Case Report on Controlled Remission of Symptoms by a Dietary Strategy. Front. Med. 2018 |
13. Donaldson MS, Speight N, Loomis S. Fibromyalgia syndrome improved using a mostly raw vegetarian diet: An observational study. BMC Complement Altern Med. 2001; 1: 7.
14. Rodrigo L, Blanco I, Bobes J, and de Serres FJ. Clinical impact of a gluten-free diet on health-related quality of life in seven fibromyalgia syndrome patients with associated celiac disease. BMC Gastroenterol. 2013; 13: 157.
15. Curtis K, Osadchuk A, Katz J. An eight-week yoga intervention is associated with improvements in pain, psychological functioning and mindfulness, and changes in cortisol levels in women with fibromyalgia. J Pain Res. 2011 ;4:189-201.

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May 15, 2018

Osteoporosis: Don’t Let it Sneak Up On You!


In this post we’ll be talking about osteoporosis, which is characterized by bone that has become porous and low density, leading to bone fractures. Osteoporosis is a particularly large problem for post menopausal women, commonly resulting in fractures of the hip, wrist and spine. You may have observed the characteristic “hump back” slumping spine associated with osteoporosis, often seen in older people. In this post we’ll delve into the etiology of osteoporosis and what can be done to prevent and potentially even reverse this condition.

Don’t let it sneak up on you

Osteoporosis can be a “silent killer” that strikes without warning, especially as we get older. It is not uncommon for people to discover they have osteoporosis when a minor impact like a bump or even simply sitting down too quickly results in a fracture. For this reason it is important for people to monitor their bone mineral density as they reach middle age, and especially into older age. Osteoporosis is characterized by low bone density, which makes bone brittle, weak and easily fractured.

We’ll get into bone mineral density testing in more detail later, but first let’s jump into how osteoporosis develops.

Bone remodeling

Bone in the body is constantly being remodeled, which is a process of bone breakdown (resorption) and formation (deposition). Low bone density and osteoporosis occur when the rate of bone resorption exceeds the rate of bone deposition. The early stages of low bone density are called osteopenia, which can later develop into osteoporosis. Whether your bones are still nice and dense, or you have osteopenia, or even osteoporosis, there is a lot you can protect your bones and prevent fractures, so keep reading!

Prevalence of osteoporosis

Osteoporosis causes almost 9 million fractures per year worldwide, many of which happen in western countries like the United States. Overall, women are disproportionately affected, and make up 61% of osteoporotic fractures (1). In women over age 45, osteoporotic fractures account for more time spent in the hospital than many other diseases, including diabetes, myocardial infarction and breast cancer (2). Although women are more commonly affected, the consequences are grim for men as well. Although women suffer fractures more often, men have higher rates of fracture-related mortality. In fact, in the six months following a fracture, the mortality rate was about double that of similarly aged women (3).

Causes of osteoporosis

Many factors can contribute to osteoporosis and it’s often not simply a matter of having enough calcium.

Other contributing factors:

  • Poor nutrient absorption
    • Important bone minerals and fat-soluble nutrients must be absorbed to be utilized
  • Vitamin D deficiency
    • Necessary for the body to absorb and utilize calcium
  • Vitamin K2 deficiency
    • This vitamin found in fermented foods like sauerkraut directs serum calcium to be stored in bone
  • Other important bone mineral deficiencies:
    • Magnesium
    • Boron
    • Phosphorous
  • Sedentary lifestyle
    • Weight-bearing exercise in particular is important to promote bone deposition and adequate bone density
  • Smoking
    • Associated with an increased risk of fracture
  • Certain medications
    • Corticosteroids like prednisone and cortisone
  • Hormone imbalance
    • Estrogen deficiency in women
    • Post menopausal changes in hormones
    • Testosterone deficiency in men
    • Parathyroid hormone
    • Growth hormone
    • Thyroid disease

As we can see, many factors contribute to osteoporosis. It’s important to determine what root cause is underlying low bone density and work from there. In addition, bone density drugs like Fosamax may actually contribute to fractures!


Several drugs like Fosamax (alendronate sodium) are in a category of drugs known as bisphosphonates which appear to increase bone density but may actually contribute to atypical fractures. One such study found that subtrochanteric insufficiency fractures were more common in post-menopausal women taking Fosamax and that the prolonged drug therapy may contribute to these fractures (4). Long-term Fosamax use for ten years or longer is associated with atypical femoral fractures in the shaft of the bone instead of the femoral neck.

Another larger retrospective review found similar increased prevalence of low-energy femoral shaft fractures associated with Fosamax use. They found that Fosamax use was a significant risk factor in the occurance of this type of fracture and that this fracture pattern was 98% specific to Fosamax users. The researchers suggest that this may result from diminished osteoclast activity and a resulting reduction in ability to repair stress fractures (5). Due to suppressed bone turnover, small cracks in the bone are unable to heal and lead to fractures over time as they become more numerous.

As we can see, the current conventional approach to managing bone density and osteoporosis leaves a lot to be desired. Now that we know some of the major players and understand a bit about how osteoporosis develops, let’s switch gears and get into solution mode. Next, we’ll look at natural treatments that can improve bone density, strengthen bone and assist with fracture healing.

Building healthy bones

It’s easy to tell from some of the causes of osteoporosis above some of the ways to prevent bone loss. Ensuring adequate intake and absorption of key nutrients like Vitamin D, Vitamin K2 and minerals like calcium, magnesium and boron is critical. In addition, regular weight-bearing exercise and maintaining hormone balance can be very important. We’ll cover resistance training but let’s first talk about hormone balance in more detail before getting into nutrition and other factors that play a role in osteoporosis.

Hormone balance

The demographics of osteoporosis reveal the importance of hormone balance in osteoporosis, which primarily affects older, post-menopausal women. This risk largely revolves around lower levels of estrogen, a hormone that impacts bone density. After menopause, estrogen levels fall and the rate of bone resorption (breakdown) overtakes the rate of bone formation, leading to bone loss.

Black cohosh

Black cohosh can help to support healthy estrogen levels, and it has a positive impact on BMD as a result. One trial of 62 postmenopausal women found that 40mg of black cohosh per day increased osteoblast activity and had a positive effect on bone remodeling (6). Another study evaluated the effect of black cohosh on rats and found that it has bone sparing properties. Researchers also suggest that black cohosh may prevent osteoporosis in older men, so it may be helpful for both sexes (7).


Dehydroepiandrosterone (DHEA) is a precursor to both estrogen and androgen hormones. DHEA levels decline with age and reduced levels are believed to contribute to many age-related changes impacted by sex hormones, including bone density. One trial of 28 men and women in their early to mid 70s with low DHEA levels compared 50mg of DHEA per day to a placebo and found that bone mineral density (BMD) improved in the active group. In addition, fat mass decreased in the DHEA group and they also experience increased serum IGF-1 and testosterone levels (8).

A larger study of 225 healthy adults aged 55 to 85 years found similar results. In this trial, serum IGF-1, testosterone and estradiol all increased in women but not men, and lumbar BMD increased as well. Although there was no increase in BMD for men overall and no increase in hip, femoral neck or total body BMD for women, authors conclude DHEA confers a modest benefit to women. This cohort was made up of healthy (non-osteoporotic) adults, and it would be interesting to see if results might be more impressive in people with low BMD (9).

Next, let’s transition away from hormones and talk about the importance of healthy digestion and nutrient absorption before moving onto the critical nutrients for osteoporosis themselves.

Are you absorbing your nutrients?

One commonly overlooked contributing factor in osteoporosis is impaired digestion that prevents important bone nutrients from being absorbed and utilized to form health, dense bone. The best diet and supplementation will have little impact if the GI tract is not functioning properly. For this reason, it is important to make sure digestion is working properly early on.

As we’ve already begun to see, managing bone density is not as simple as merely consuming calcium, whether from dietary sources, supplements, or a combination of the two. Important bone minerals including calcium, boron, magnesium and phosphorous require strong stomach acid to be absorbed. Hypochlorhydria, or low stomach acid can contribute to low bone mineral density by preventing the absorption of these minerals. Hypochlorhyria, in turn, can result from many different causes.


One primary cause of low stomach acid, especially as it relates to osteoporosis, is age. Stomach acid production declines with age and results in impaired mineral absorption. Other causes include GI infections like H. pylori and parasitic infections. If stomach acid is low, it is important to correctly identify the upstream cause and work to treat that issue. Consider working with a functional medicine practitioner to be sure you correctly identify and treat your upstream cause, as osteoporosis can result from multiple causes.

SIBO connection

Small intestine bacterial overgrowth is well known to cause hypochlorhydria, and can be an underlying cause of osteoporosis (10). Because SIBO is fairly common and can contribute to so many problems in addition to osteoporosis, consider a SIBO breath test if symptoms warrant. Other common symptoms of SIBO primarily include digestive disturbances like gas, bloating, diarrhea and abdominal pain or cramping. Mood can also be affected, with symptoms of depression or anxiety being common.

Celiac disease

In addition to SIBO, other digestive disorders are commonly implicated as root causes of osteoporosis and low bone mineral density. Celiac disease is another well established root cause which impedes dietary mineral absorption. A systematic review of celiac patients found that adherence to a gluten free diet for five years resulted in normalized bone mineral density. One of the included studies found that a gluten free improved bone mineral density as well as bisphosphonate drugs (11).

Poor fat absorption

Another digestive-related cause of osteoporosis is poor fat absorption. You may have noticed in the earlier section both Vitamin D and Vitamin K2 are critical for bone health. Vitamin A, another fat soluble nutrient, is important as well. Because these are both fat-soluble nutrients, they rely on fat to absorb. And because we must eat fat with fat-soluble nutrients in order to absorb them, people on low-fat diets may become deficient even though they eat many foods rich in these nutrients. Poor fat digestion resulting from gall bladder removal or gallstones is another possible cause of deficiency.

Important nutrients

In this section we’ll discuss the most important nutrients to support increased bone density.


Calcium is the most prevalent mineral in the body. Although some studies have shown no benefit to calcium supplementation, many have been poorly designed in light of what we now know about all the nutrients that are required to build bone. Many of these studies used only calcium carbonate, which is very poorly absorbed and has a strong alkalizing effect on stomach pH. In fact, calcium carbonate is the active ingredient of Tums, the popular over the counter heartburn medication, which temporarily relieves symptoms by alkalizing stomach acid.

Because of calcium carbonate’s alkalizing effect on stomach pH, it may actually do more harm that good because very acidic stomach acid is critical to absorbing nutrients. Some studies use calcium carbonate as a control, which may contribute to somewhat misleading data because carbonate may be contributing to worse outcome for the control group.

Another form of calcium that is much more effective is known as MCHA calcium, which stands for microcrystalline hydroxyapitate. The body uses this form to create bone matrix and some research shows supplementary MCHA calcium (also sometimes called MCHC) is an especially beneficial form. Many MCHC supplements are made from whole animal bones and supply a whole complex of necessary nutrients like collagen and trace minerals such as boron, potassium, zinc and copper that are used to construct the bone matrix. They also typically contain vitamins D and K2. These products are also sometimes referred to as “ossein-hydroxyapitate complex” supplements, or OHC in research.

MCHA Calcium

A number of clinical trials have evaluated the benefits of MCHA / OHC calcium by comparing its effects to those of calcium carbonate supplements in patients with osteopenia and osteoporosis, and found benefit. One such study followed a cohort of 54 women for three years and found statistically significant improvements in bone density and serum osteocalcin in the MCH calcium group (12).

A 2015 meta analysis of studies from 1966 to 2013 compared the benefits of OHC calcium supplements to calcium carbonate and concluded that the OHC form was superior to “calcium [carbonate] supplements in maintaining bone mass in postmenopausal women and in different conditions related to bone loss.” They also observed that in patients with osteopenia or osteoporosis who took OHC, pain symptoms were decreased and fractures healed more quickly (13).

In addition to other trace minerals important for bone health, MCH / OHC calcium also contain fat-soluble vitamins like vitamin D and K2, which are important as well. Without these other nutrients in addition to calcium, bone density may not be improved and calcium supplements alone can contribute to kidney stones.

Vitamin D

It’s well known that optimal vitamin D levels are critical for bone health. Dietary vitamin D increases calcium absorption and adequate blood levels are associated with significantly reduced risk of fracture (14). Of course, significantly elevated levels of vitamin D can also be problematic, so we like to keep blood levels between 35-60 ng/dL.

Vitamin K2

This important nutrient fulfills several job duties in the body related to bone density. It is a cofactor in the carboxylation of osteocalcin, which promotes normal bone mineralization and appears to regulate the growth of hydroxyapitate crystals. A number of animal studies demonstrate the vitamin K2 improves bone density in rats that are ovariectomized or treated with glucocorticoids like prednisone. It appears to stimulate bone formation and suppress bone resorption, or breakdown.

In human clinical trials, vitamin K2 has been demonstrated to support lumbar bone mineral density and prevent osteoporotic fractures with age-related osteoporosis and prevent vertebral fractures associated with glucocorticoid use. It also increases bone density of extremities in patients with cerebrovascular disease and maintains lumbar bone mineral density in liver-dysfunction induced osteoporotic patients (15).

One well-designed clinical trial on a cohort of 63 postmenopausal women in Indonesia found that adding 45mg of vitamin K2 to 1500mg of calcium carbonate per day significantly increased lumbar bone mineral density and decreased undercarboxylated osteocalcin levels over a 48 week treatment period (16).

Japanese research has corroborated these findings in a few studies which used 30-45mg of Vitamin K2 per day to increase bone density. One such trial from 2010 found that 45mg of Vitamin K2 daily prevented fractures and sustained lumbar bone mineral density in a cohort of 241 osteoporosis patients (17). A similar European study found similar benefit in a smaller sample size. Researchers suggest that Vitamin K2 therapy should be started early, starting at menopause to effectively prevent spine bone mineral density loss (18). Other research on Caucasian women has found similar benefit as well, confirming that Vitamin K2 is an effective way to prevent bone loss in multiple ethnicities of women (19).

Vitamin A

The last fat soluble nutrient we’ll talk about is Vitamin A, which at high doses is associated with increased risk of fracture. One review study found that high retinol (the active form of Vitamin A from animal sources) induces fractures in animals, and asserts that intake double the recommended amount can cause adverse effects in females. This is only true for retinol and not pro-vitamin A precursors like beta carotene.

One factor that we were not able to find more information on was the ratio of Vitamin A to the other fat-soluble vitamins. It is fairly well established at this point that the fat-soluble vitamin levels must remain in correct proportions to each other, and Vitamins A and D in particular protect against toxic levels of each other. It would be interesting to know what the nutrient status for Vitamin D was in these patients.

Other therapy options

In addition to these nutrients there are some other therapies that have shown benefit for maintaining and restoring bone mineral density, which we’ll cover in the following section.

Genistein and soy

Certain soy foods and other genistein-containing foods have also shown to be very helpful. Found in soy, fave beans, garbanzo beans and coffee, genistein is an phytoestrogenic isoflavone that shows promising benefits for bone mineral density and osteoporosis. In fact, genistein has the strongest estrogenic activity of any flavone, which makes it a great treatment option for menopausal osteoporosis.

Eating fermented soy in moderate quantities is a great way to get more genistein into the diet. Miso, tempeh and natto are all great sources of genistein. It is important, however to keep quality in mind, as more than 90% of soy grown at this point is genetically modified. When selecting soy products, there are two main labels to look for: organic and non-GMO. These labels ensure that the product is non-GMO.

A well-designed trial of 389 osteoporotic postmenopausal women found that 54mg of genistein aglycone combined with calcium and vitamin D3 increased bone mineral density compared to calcium and D3 alone over a 24 month period. One possible area of concern with phytoestrogens is possibly raising the risk of estrogen-based cancers like breast cancer. To address that concern, this study also measured markers for breast cancer including BRCA1 and BRCA2 expression and mammography and found that gene expression did not increase and mammographic density did not change significantly (20). These results suggest that genistein is safe and effective in postmenopausal women.

Other research has found supporting evidence in rats (21) and postmenopausal women (22) (23). It is unclear whether this research would extend to premenopausal women or men. Both of these human studies used a dose of 54mg of genistein per day.

Genistein supplements are also available, and there are a few non-GMO options, including:

  • Source Natural Genistein
  • Bluebonnet non-GMO Soy Isoflavones Plus Genistein

These are both isoflavone complexes that also contains daidzen and glycitein.

Another option that is more of a bone building complex, combining genistein with vitamin D3, vitamin K2, calcium, magnesium and zinc is:

  • Designs for Health Osteoben

In addition to these nutrients, one constituent of cannabis has research also has some research behind it.


Cannabidiol (CBD) is a non-psychoactive constituent of marijuana. One study found that the administration of CBD enhanced the healing of femoral fractures in rats. This action was not seen in administration of THC alone, which is the main psychoactive component of marijuana. CBD increased production of an enzyme that catalyzes lysine hydroxylation, which in turn is involved in collagen crosslinking and stabilization. This effect led to CBD improing fracture healing (24).

Magnet therapy

One last treatment option with some research behind it is magnet therapy. One rat study found that long-term extremely low frequency magnetic field (ELFMF) was effective at increasing bone mineral content and bone mineral density. In addition, bone specific alkaline phosphatase levels were increased in the ELFMF group, leading researchers to conclude that ELFMF may offer benefits in the treatment of osteoporosis (25).

Resistance training

We mentioned the important of weight-bearing exercise earlier. Quite a bit of research confirms the importance of this type of exercise in preventing bone mineral density loss as we age. The importance of weight-bearing exercise cannot be overstated, and it’s a “better late than never” type of thing. No matter at what age one begins weight bearing exercise, it is a critical piece to slow and stop bone mineral loss, and can even help increase bone mineral density in some cases. By creating a mild positive stress, or eustress, on the bones, it triggers them to increase their strength and mineral composition.

A 1999 review study found that out of nearly two dozen trials evaluating the effects of resistance training found that the vast majority showed “a direct and positive relationship between the effects of resistance training and bone density,” and the few that did not show a benefit may have been poorly designed (26). A more recent study compared weight bearing exercise to non-weight bearing in a cohort of 40 osteoporosis patients in their 60s. Compared to the non-weight bearing exercise group, the weight-bearing group showed more impressive increases in bone mineral density as well as overall quality of life (27).

Despite concerns that using heavy weight for resistance training could lead to fracture, one Australian study found that heavy weights may actually confer a greater benefit than moderate weight. Participants completed either a high weight resistance training program or a low intensity program of the same duration and dose. The heavy weight group improved in height, bone mineral density and functional performance compared to the low intensity group (28). And best of all, there were no injuries! A patient’s initial bone mineral density should be considered to make sure the weights used are appropriate.

Although much of the research presented so far has focused primarily or exclusively on women, this trial evaluated the effects of resistance training on men, noting that although women are affected more by osteoporosis, 40% of osteoporotic fractures occur in men and that men have significantly greater risk of complications after a hip fracture. Coupled with the fact that men are treated far less often than women and more than 90% of osteoporosis in men goes undiagnosed and untreated, this represents a significant issue for men, especially older men (29).

This trial concluded that both resistance training and jump training, which revolves around jumping exercises increased bone mineral density in men with a mean of 44 years. Osteocalcin was also increased significantly. Resistance training appeared to be the most effective, resulting in more robust bone mineral density increases.

Based on this research and more that was not included here for brevity, resistance training and especially high intensity interval training (HIIT) is extremely important for anyone concerned about bone mineral density and must be included as part of any well-rounded treatment plan. Despite its placement towards the end of this article, it is a critical piece of the osteoporosis puzzle!

In conclusion

Osteoporosis is a significant health problem today, and the bisphosonate drugs commonly used to treat low bone mineral density have significant risks, including not reducing the risk of fracture, or in some cases even increasing that risk! Fortunately, there are many natural treatment options for osteoporosis that are safe and effective. By working with a functional medicine practitioner to correctly identify and treat your root cause, you can prevent or even reverse osteoporosis from developing and leading to a debilitating fracture.

General recommendations for Osteoperosis concern:

  • Weight lifting / resistance training 2-3 days per week, plus short (10-30 mins) High Intensity Interval Training (HIIT) sessions 4-5 days per week.
  • Achieve Vitamin D levels in the blood of 35-60 ng/ml. If supplementing with Vitamin D, be sure to also supplement with Vitamin K2 (see below for specifics).
  • Ensure that you are getting adequate calcium from food (preferred) or if supplementing, use the MCHA form. It is best to get between 800-1300mg of calcium each day, optimally from foods.
  • Vitamin K2 at 15-45mg per day (note that this is mg dosing and many MK-7 Vitamin K2 supplements are in mcg. Usually the MK-4 form will be required to get the 15-45mg per day dosing in a cost-effective way).
  • For post-menopausal women, consider 40mg per day of black cohosh and/or 54mg daily of genistein aglycone (can also consider organic miso, tempeh, and natto consumption if soy is tolerated).
  • If additional support is needed or desired, CBD and/or magnet therapy may be helpful (though there is not enough research to be conclusive on either of these. However, because they are generally safe and well-tolerated, it can be worth pursuing. Please note that magnet therapy is not to be used for anyone with a pacemaker).
  • We do not recommend supplementing with DHEA (a hormone) outside of working with a functional medicine doctor who understands this hormone and is measuring blood levels.


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  11. Grace-Farfaglia P. Bones of Contention: Bone Mineral Density Recovery in Celiac Disease—A Systematic Review. Nutrients. 2015;7(5):3347-3369. doi:10.3390/nu7053347.
  12. Ciria-Recasens, Manel, et al. “Comparison of the Effects of Ossein-Hydroxyapatite Complex and Calcium Carbonate on Bone Metabolism in Women with Senile Osteoporosis.” Clinical Drug Investigation, 2011, p. 1., doi:10.2165/11592930-000000000-00000.
  13. Castelo-Branco, C., and J. Dávila Guardia. “Use of Ossein–Hydroxyapatite Complex in the Prevention of Bone Loss: a Review.” Climacteric, vol. 18, no. 1, 2014, pp. 29–37., doi:10.3109/13697137.2014.929107.
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  17. Shiraki, Masataka, et al. “Vitamin K2 (Menatetrenone) Effectively Prevents Fractures and Sustains Lumbar Bone Mineral Density in Osteoporosis.” Journal of Bone and Mineral Research, vol. 15, no. 3, 2010, pp. 515–521., doi:10.1359/jbmr.2000.15.3.515.
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  19. Knapen MHJ, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporosis International. 2007;18(7):963-972. doi:10.1007/s00198-007-0337-9.
  20. Marini, Herbert, et al. “Breast Safety and Efficacy of Genistein Aglycone for Postmenopausal Bone Loss: A Follow-Up Study.” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 12, 2008, pp. 4787–4796., doi:10.1210/jc.2008-1087.
  21. Bitto, A, et al. “Effects of Genistein Aglycone in Osteoporotic, Ovariectomized Rats: a Comparison with Alendronate, Raloxifene and Oestradiol.” British Journal of Pharmacology, vol. 155, no. 6, 2008, pp. 896–905., doi:10.1038/bjp.2008.305.
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  24. Kogan, Natalya M, et al. “Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.” Journal of Bone and Mineral Research, vol. 30, no. 10, 2015, pp. 1905–1913., doi:10.1002/jbmr.2513.
  25. Akpolat, Veysi, et al. “Treatment of Osteoporosis by Long-Term Magnetic Field with Extremely Low Frequency in Rats.” Gynecological Endocrinology, vol. 25, no. 8, 2009, pp. 524–529., doi:10.1080/09513590902972075.
  26. Layne, Jennifer E., and Miriam E. Nelson. “The Effects of Progressive Resistance Training on Bone Density: a Review.” Medicine & Science in Sports & Exercise, vol. 31, no. 1, 1999, pp. 25–30., doi:10.1097/00005768-199901000-00006.
  27. Shanb AA, Youssef EF. The impact of adding weight-bearing exercise versus nonweight bearing programs to the medical treatment of elderly patients with osteoporosis. Journal of Family & Community Medicine. 2014;21(3):176-181. doi:10.4103/2230-8229.142972.
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  29. Hinton PS, Nigh P, Thyfault J. Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: a 12-month randomized, clinical trial. Bone. 2015;79:203-212. doi:10.1016/j.bone.2015.06.008.
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February 12, 2018

Iron Man: Lab Markers for Iron Deficiency

Iron Deficiency

by Aaron Mello, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

We wrote in a recent post about functional laboratory testing for anemia. Different forms of anemia result from many different causes, and iron deficiency anemia is the most common form. In this post we’re going to expand on iron dysregulation and some other sequelae of iron deficiency. We’ll also get into markers for iron status that weren’t covered in the anemia post, so keep reading to learn more!

Most of the iron in the body is found in hemoglobin, which is utilized by RBCs to make oxygen transport possible. Much of the remaining iron not utilized by hemoglobin is bound by proteins like transferrin and ferritin because free iron must be tightly regulated to prevent damage. Free iron is extremely reactive and can also be utilized by pathogenic bacteria to proliferate (1).

In this post we’ll go into more detail about iron status markers and iron deficiency, whereas in the previous post on anemia we concentrated more on the RBC section of the CBC. We’ll be focusing on the other side of the coin, iron overload, in an upcoming post. To learn more about how to evaluate iron status and identify iron deficiency, keep reading! We’ll talk about several iron markers, including ferritin, transferrin, serum iron, TIBC, UIBC and iron saturation.

Roles of iron in the body

Let’s begin by talking about how the body utilizes iron in more detail. In our previous post about anemia, we wrote about iron deficiency anemia, which is one of the main consequences of iron deficiency. Other sequelae of iron deficiency we’ll discuss here include heart issues; dry, damaged skin and hair; restless leg syndrome; pica and brittle or spoon-shaped fingernails. Many of these symptoms result from inadequate oxygenation, and as we’ll see from a study we’ll get to shortly, iron deficiency symptoms can be present even without a diagnosis of anemia.

Nitric oxide production is iron-dependent

In addition to negatively impacting the body’s ability to transport oxygen, iron deficiency also reduces the body’s ability to synthesize nitric oxide (NO), which dilates blood vessels. Iron is a necessary cofactor for NO synthesis, so iron deficiency impairs blood vessel dilation is impaired. It’s not just that oxygen can’t be transported, it’s that the flow of blood to peripheral tissues is also impaired due to a lack of NO (2).

Iron necessary for liver detoxification

Iron is not just limited to oxygen transport and utilization. Iron is also a critical nutrient for the function of many cytochrome enzymes, including cytochrome P450 enzymes that are responsible for liver detoxification (2). Consequently, iron deficiency can downregulate phase 1 liver detoxification. Iron also relates to thyroid health, which we wrote about several months ago in a post on Hashimoto’s thyroiditis.

Peroxidase enzymes need iron

Thyroid peroxidase enzyme (TPO) synthesizes thyroid hormone and is dependent on iron. Consequently, thyroid hormone production may fall in iron deficiency. TPO uses hydrogen peroxide (H2O2) to ready iodine for thyroid hormone production. Myeloperoxidase (MPO) is another iron-dependent peroxidase enzyme that controls pathogenic bacteria by producing sodium hypochlorite (NaClO), or bleach, from hydrogen peroxide in order to kill pathogens. MPO malfunction can lead to immune function failure, gut infections and dysbiosis.

Catalase is a third iron-dependent enzyme. It converts hydrogen peroxide (H2O2) to water in order to control levels of H2O2 and prevent cellular and metabolic damage. Free iron that is not bound by a protein can be particularly destructive in the presence of H2O2, with which it can interact to produce dangerous hydroxyl radicals (OH), which causes more damage than just H2O2 or free iron alone (3). It’s easy to see from these examples how far-reaching the roles of iron are.

Like many nutrients, there is a sweet spot for iron levels, and this is doubly true given its role in many metabolic processes, as well as its potential to cause damage. Next we’ll discuss the context of iron deficiency anemia in the larger picture of health before moving on to heme vs non heme iron and some other nutrients required to utilize iron properly.

Anemia is priority

Let’s pause for a second, zoom out and reorient ourselves in the larger picture of health. In challenging patients it can be tempting to sometimes deprioritize anemia and focus on what may appear to be more pressing concerns. Although there may be situations where this is necessary, they are generally few and far between, especially in the chronic disease world. Because nearly every biochemical process in the body is energy dependent – that is – requires ATP, anemia affects every cell with mitochondria and every system in the body.

For this reason it’s often advisable to get the anemia patterns straightened out early on, before moving on to other areas of treatment, unless there is a good reason to start somewhere else first. With that bigger picture in mind, let’s zoom back in and review the importance of heme vs non-heme iron.

Heme vs non-heme iron

One big determining factor for iron intake is the form of iron an individual is consuming. Non-heme iron from vegetarian sources is poorly absorbed and utilized compared to heme iron in meat, especially red meat. This can be an issue for long-term vegans and strict vegetarians, especially those who do not eat any shellfish, which are also a good source of heme iron. Non-heme iron is typically present in an oxidized form, whereas iron needs to be in its reduced form in order to be absorbed (4).

Other factors that affect iron absorption include vitamin C, which increases absorption of non-heme iron by reducing it into more absorbable form (5). Vegetarians who want to increase absorption of plant-based non-heme iron can try consuming with Vitamin C with food. On the other hand, plant foods contain phytates and polyphenols that inhibit iron absorption, so properly soaking seeds and grains before eating is also important to maximize iron absorption.

Calcium also blocks absorption of iron, so calcium-rich foods like spinach and dairy may reduce absorption of iron from iron-rich foods (6). To raise iron levels, concentrate on isolating calcium-rich foods to one meal per day and have another meal that is rich in iron foods like red meat, liver and clams. Now that we’ve covered these factors affecting iron absorption, we’ll next discuss the role copper and vitamin B6 play in iron regulation.

Vitamin B6 and copper

Vitamin B6 and copper affect the body’s ability to absorb and utilize iron. B6 in particular is required to absorb iron. One study on anemic pregnant women treated with iron supplements found that the women who did not initially improve were deficient in B6 and after adding B6 to the iron supplement, anemia improved (7). In addition, both B6 and copper are involved in the utilization of iron to synthesize RBCs.

Copper has a complicated relationship with iron. On the one hand, copper can impede iron absorption by binding to mucosal transferrin at the expense of iron, and excess copper inhibits the ability of spleen reticuloendothelial cells to reuse iron (8). On the other hand, copper is also needed to mobilize sequestered iron from storage tissues. Similar to B6, this can lead to a form of anemia that does not respond to iron supplementation unless copper is also added (9).

It can be worth looking at B6 and copper status and intake in cases of anemia, especially if there are other clues present. Other indicators that copper and B6 may be involved are mood and temperament issues. B6, copper and zinc are required for neurotransmitter synthesis and zinc/copper balance can contribute to aggressive behavior, deficiencies or imbalances in these nutrients may manifest as symptoms of mood, anxiety or temperament (10).

High levels of zinc supplementation for prolonged periods of time without copper supplementation can lead to copper deficiency. This is worth noting for people who supplement with zinc.

Next we’ll talk a bit more about iron deficiency before moving on to related laboratory markers.

Iron deficiency

Iron deficiency is the most common nutritional deficiency worldwide (11). The most prominent consequence of iron deficiency is iron deficiency anemia, which is also the most common form of anemia. Iron deficiency reduces the ability’s body to transport oxygen via iron-containing hemoglobin on RBCs and results in classic anemia symptoms like fatigue, shortness of breath, pale skin and brittle nails.

Although iron deficiency anemia is the main consequence of deficiency, it’s not the only one. We mentioned a study in the introduction about non-anemic iron deficiency. It found that in a population of 198 menstruating women with low ferritin but normal hemoglobin, oral iron supplementation improved fatigue symptoms (12).

Other iron deficiency issues can include:

  • Heart abnormalities like irregular heartbeat, heart palpitations, and in extreme cases enlarged heart, heart murmur or failure
    • When cells are starved of oxygen, the heart must work harder to circulate more RBCs because they can’t carry much oxygen
    • Compounding the issue, the heart itself may lack sufficient oxygen for muscle contractions
  • Dry, damaged skin or hair (13)
    • In a mouse model, reversal of iron deficiency led to a restoration of hair growth
    • Iron deficiency may contribute to hair loss by inhibiting the iron-dependent ribonucleotide reductase enzyme, which is a rate-limiting enzyme for DNA synthesis
    • Hair and skin cell lines both turn over rapidly
  • Restless leg syndrome (RLS)
    • RLS can result from many different causes but iron deficiency is a common cause (14)
    • One study of 251 iron deficiency anemia patients found that RLS was nine times more prevalent in their group than the general population (15)
  • Pica
    • Pica is a condition of craving or eating dirt
    • It can result from many causes, some psychological
    • Iron deficiency pica is characterized by a compulsion to consume iron-containing substances like clay, soil and even small rusty pieces of steel
  • Pagophagia (pica for ice) may also indicate iron deficiency (16)

Because iron plays a central role in transporting and utilizing oxygen to produce ATP, it’s important to resolve iron deficiency and anemia early on in care. Countless critical processes in the body are energy dependent, and if cells are starved for energy they are not going to function properly. In this way, iron deficiency can be central to many diverse health conditions. Next, let’s shift gears and talk in more detail about iron status markers.

Iron status markers

In addition to the anemia markers on the CBC we discussed in our previous post, iron status markers are helpful in cases of suspected iron deficiency anemia or iron overload. In this section we’ll go into more detail about each of the markers and how to use them clinically. As we mentioned earlier, iron is tightly regulated by the body because of its massive reactive potential and the ability of pathogens to use iron to their advantage (17).

In addition, the body has no way to eliminate excess iron other than bleeding and menstruation, so iron status is dependent on two factors – dietary iron intake coupled with how iron is utilized and stored in the body. As mentioned previously, the body strives to keep most iron either in use in hemoglobin or bound to proteins like transferrin and ferritin to prevent free iron ions from creating oxidative stress and encouraging the proliferation of pathogenic bacteria.

With anemia we are looking primarily at cells – RBCs and their components like hemoglobin. These markers are found on a standard CBC.In contrast, the markers on a complete iron panel are not part of a CBC and must be ordered separately to confirm or rule out suspected iron deficiency or overload. We’ll get into each of these iron panel markers in more detail now, as well as a few other markers that can be relevant.

Ferritin: our preferred functional range is 50-150 ng/ml* (Iron Disorders Institute prefers 25-75 ng/ml for those with hereditary hemochromatosis and for anyone levels above 100 ng/ml may indicate an increased disease risk*)

Iron is bound to ferritin to create iron stores in tissues including the liver, spleen and bone marrow. Depressed ferritin may indicate iron depletion, but many factors can affect ferritin and it’s best to view it in the context of a full iron panel. Ferritin sequesters iron in long-term storage to prevent free iron from causing oxidative stress and to make it unavailable to pathogens which will use it for their own growth.

Ferritin on its own without other markers for context can be misleading, as several factors such as oxidative stress and inflammation can elevate ferritin levels. Inflammation can mask iron deficiency and result in a false normal ferritin level. Inflammation can be confirmed by running hsCRP, which we’ll talk about shortly.

Other possible influences on ferritin levels include intake of sulfuraphane (18), milk thistle (19) and green tea extract (20), which can all upregulate ferritin. These products can also lead to anemia by causing the body to store more iron and diverting it away from hemoglobin. Ferritin is also elevated in liver damage, hemochromatosis, neurodegenerative diseases and in response to inflammation.

As we can see, ferritin is impacted by many factors. It also has antioxidant properties, and factors that increase synthesis of glutathione and catalase also increase ferritin because it’s part of the antioxidant defense system (21). Because many biochemical causes can impact ferritin and potentially cancel each other out, it is important to view ferritin in the context of other markers on a complete iron panel, which we will discuss now.

* Cardiovascular and blood sugar disease risk increases with ferritin levels above 100 ng/ml. However, these risks can be mitigated with properly functioning antioxidant defense mechanisms. With properly functioning antioxidant defense, levels of 150 ng/ml or above may be safe.


The protein transferrin is largely synthesized in the liver and binds iron for transportation through the blood. In addition to binding iron for transport, transferrin is a major component of iron regulation primarily found in the blood and tissue fluids (22).

Serum transferrin is a somewhat expensive test. We sometimes order TIBC instead, which we’ll talk about shortly, as TIBC can be an indicator of transferrin status. Other factors influencing transferrin include liver disease, which can reduce synthesis, and dietary iron. Transferrin can vary considerably based on the iron content of a person’s last meal, so it needs to be performed with the patient fasting.

Serum iron: 

This is simply the amount of iron in the bloodstream bound to transferrin. It is not the most reliable marker of iron deficiency but it’s a better marker for iron overload like hemochromatosis, especially when combined with iron saturation. We’ll talk more about hemochromatosis in an upcoming post.

TIBC: our preferred functional range is 275-430 ug/dL

Total iron binding capacity (TIBC) measures ability of RBCs to bind to transferrin. TIBC is elevated in iron deficiency, pregnancy and blood loss, and it’s normal in anemia of chronic disease and inflammation. TIBC is depressed in elevated iron loads, liver disease, hypoproteinemia, infection and chronic disease.

UIBC, or unbound iron binding capacity, has an optimal range of 175-350 ug/dL. Lower levels mean higher iron.

Transferrin saturation: our preferred functional range is 17-45% with optimal being 25-35%

Elevated transferrin saturation (TS) stimulates hepcidin, which we’ll talk about next. In turn, hepcidin downregulates iron absorption and increases storage of iron in ferritin. TS is more sensitive than ferritin because TS is what causes ferritin to increase in response to high iron. It’s also more specific to iron status than ferritin, which is influenced by many other factors like inflammation, which we discussed earlier.

Hemoglobin (Hg): 

Hemoglobin is the iron-containing portion of a red blood cell that transports ozxygen from lungs to tissues. Depleted or excessive amounts of hemoglobin can point to imbalanced iron levels.

Mean Corpuscular Volume (MCV):

MCV is a measure of the average volume of red blood cells. Anemias are often referred to in reference to the size of the red blood cell. There is microcytic anemia (low MCV and often is caused by low iron), normocytic anemia (normal MCV), and macrocytic anemia (high MCV – also called pernicious anemia – often caused by low B12 and/or folate levels).

Gamma Glutamyl Tranferase (GGT):

GGT is a liver enzyme that has traditionally been used to primarily look for liver issues. Recently, it has become clear that GGT elevation (even high-normal values) can be associated with increased risk for metabolic syndrome. Levels greater than the lowest 25% of the population are associated with metabolic abnormalities, cardiovascular disease risk, and more.


Sometimes referred to as “The Iron Regulatory Hormone,” hepcidin is the master coordinator of iron. High iron hepcidin downregulates iron absorption and directs free iron to be sequestered in ferritin. Hepcidin responds to threats like an infection via inflammation which could use free iron for its own proliferation. Hepcidin also has antimicrobial properties; in fact its name comes from the its location of synthesis, the liver (hep-), and its antimicrobial effects (-cidin) (23).

hsCRP: our functional range is 0-1 mg/L

We talked about hsCRP and inflammation earlier. Inflammation, as measured by high sensitivity C-Reactive Protein (hsCRP) can lead to false normal or even elevated ferritin in the presence of anemia. Anemia of chronic disease results in low absorption and high storage as ferritin, so high ferritin and iron deficiency can exist simultaneously because the small amount of iron that is absorbed is directed into storage instead of hemoglobin synthesis in an effort to sequester it away from pathogenic invaders. hsCRP isn’t an iron marker per se, but it can be useful to confirm or rule out inflammation that may be elevating ferritin.

Now that we have a better understanding of these markers and how to use them to evaluate iron deficiency, let’s review some iron-rich foods before closing. Also be sure to keep an eye out for our upcoming post on iron overload and hemochromatosis.

Iron foods

  • Clams
  • Liver / organ meat
  • Red meat – lamb, beef
  • Prunes
  • Beets
  • Venison
  • Kidney
  • Octopus
  • Oysters
  • Sardines
  • Blackstrap molasses

In Conclusion

Iron is a critical nutrient and iron is the most common deficiency worldwide. Furthermore, iron deficiency anemia is the most common form of anemia, and it impacts every cell of the body because of its role in ATP production. It’s easy to see why resolving iron deficiency is a critical piece for anyone whom is affected by it. Stay tuned for an upcoming post on the other side of the coin from iron deficiency – iron overload and hemochromatosis!

For those low in iron, here are strategies that can help increase iron stores:

  • Make sure low iron is based on lab testing, as iron can be toxic when in excessive quantities
  • Increase iron containing foods (especially those with heme iron like animal products)
  • Add vitamin C with meals (500-1000mg)
  • Contain calcium-containing foods and/or supplements to 1 meal per day (calcium blocks iron absorption)
  • Iron supplementation under the guidance of a functional medicine doctor / practitioner
  • Stop donating blood temporarily until iron stores are back up
  • Avoid chelating substances or protocols intended to chelate metals
  • Be sure you re-test labs so that you know when levels are normal and you can simply maintain
  • If you do not have success with basic practices, see a functional medicine doctor / practitioner to identify root cause issues that might be preventing iron absorption


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  2. Galleano, M. “Nitric Oxide and Iron: Effect of Iron Overload on Nitric Oxide Production in Endotoxemia.” Molecular Aspects of Medicine, vol. 25, no. 1-2, 2004, pp. 141–154., doi:10.1016/j.mam.2004.02.015.
  3. Kadiiska, Maria B., et al. “A Comparison of Cobalt(II) and Iron(II) Hydroxyl and Superoxide Free Radical Formation.” Archives of Biochemistry and Biophysics, vol. 275, no. 1, 1989, pp. 98–111., doi:10.1016/0003-9861(89)90354-8.
  4. West AR, Oates PS. Mechanisms of heme iron absorption: Current questions and controversies. World Journal of Gastroenterology : WJG. 2008;14(26):4101-4110. doi:10.3748/wjg.14.4101.
  5. Teucher, et al. “Enhancers of Iron Absorption: Ascorbic Acid and Other Organic Acids.”International Journal for Vitamin and Nutrition Research, vol. 74, no. 6, 2004, pp. 403–419., doi:10.1024/0300-9831.74.6.403.
  6. Lynch, Sean R. “The Effect of Calcium on Iron Absorption.” Nutrition Research Reviews, vol. 13, no. 02, 2000, p. 141., doi:10.1079/095442200108729043.
  7. Hisano, M, et al. “Vitamin B6 Deficiency and Anemia in Pregnancy.” European Journal of Clinical Nutrition, vol. 64, no. 2, 2009, pp. 221–223., doi:10.1038/ejcn.2009.125.
  8. Chan, W Y, and O M Rennert. “The Role of Copper in Iron Metabolism.” Annals of Clinical and Laboratory Science, vol. 10, no. 4, 1980, pp. 338–44.
  9. Sharp, Paul. “The Molecular Basis of Copper and Iron Interactions.” Proceedings of the Nutrition Society, vol. 63, no. 04, 2004, pp. 563–569., doi:10.1079/pns2004386.
  10. Walsh, W, et al. “Elevated Blood Copper/Zinc Ratios in Assaultive Young Males1.” Physiology & Behavior, vol. 62, no. 2, 1997, pp. 327–329., doi:10.1016/s0031-9384(97)88988-3.
  11. “Micronutrient Deficiencies.” WHO, World Health Organization,
  12. Clenin, G E. “The Treatment of Iron Deficiency without Anaemia (in Otherwise Healthy Persons).” Swiss Medical Weekly, vol. 147, no. 2324, 2017, doi:10.4414/smw.2017.14434.
  13. Guo EL, Katta R. Diet and hair loss: effects of nutrient deficiency and supplement use. Dermatology Practical & Conceptual. 2017;7(1):1-10. doi:10.5826/dpc.0701a01.
  14. Allen, Richard P., and Christopher J. Earley. “The Role of Iron in Restless Legs Syndrome.”Movement Disorders, vol. 22, no. S18, 2007, doi:10.1002/mds.21607.
  15. Allen, Richard P., et al. “The Prevalence and Impact of Restless Legs Syndrome on Patients with Iron Deficiency Anemia.” American Journal of Hematology, vol. 88, no. 4, Dec. 2013, pp. 261–264., doi:10.1002/ajh.23397.
  16. Uchida, T, and Y Kawati. “Pagophagia in Iron Deficiency Anemia.” The Japanese Journal of Clinical Hematology, vol. 55, no. 4, 2014, pp. 436–9.
  17. Nanami, M. “Tumor Necrosis Factor- -Induced Iron Sequestration and Oxidative Stress in Human Endothelial Cells.” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 12, Jan. 2005, pp. 2495–2501., doi:10.1161/01.atv.0000190610.63878.20.
  18. Evans PC. The influence of sulforaphane on vascular health and its relevance to nutritional approaches to prevent cardiovascular disease. The EPMA Journal. 2011;2(1):9-14. doi:10.1007/s13167-011-0064-3.
  19. Hutchinson C, Bomford A, Geissler CA. The iron-chelating potential of silybin in patients with hereditary haemochromatosis. European journal of clinical nutrition. 2010;64(10):1239-1241. doi:10.1038/ejcn.2010.136.
  20. Toolsee NA, Aruoma OI, Gunness TK, et al. Effectiveness of Green Tea in a Randomized Human Cohort: Relevance to Diabetes and Its Complications. BioMed Research International. 2013;2013:412379. doi:10.1155/2013/412379.
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December 29, 2017

Diagnosing Anemia with Functional Medicine


by Aaron Mello, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

Anemia is a complex and varied condition characterized by low levels of erythrocytes (red blood cells) and hemoglobin. There are many types of anemia. In a recent post on B12 injections, we talked about B12 deficiency anemia. In this post we’ll expand on the anemia piece and talk more about different types of anemia including iron deficiency anemia, hemolytic anemia and sickle cell anemia. We’ll also delve into some of the lab markers that are used to distinguish different types of anemia.

Anemia is a large topic so we’ll get to as much as we can in this post, and expand in future posts. We’ll also touch on ways that anemia can interact with other conditions like Small Intestine Bacterial Overgrowth (SIBO) and chronic inflammation. In addition, we’ll talk about iron and iron deficiency anemia, especially as it relates to vegan and strict vegetarian diets, which are often deficient in heme iron as well as vitamin B12. There is a lot to cover and you’re bound to learn something new, like how B12 analogues from spirulina can actually block B12 absorption! Keep reading to learn more.

Definition of anemia

For a quick recap, anemia is a deficiency of erythrocytes, or red blood cells (RBCs), which transport oxygen to all the cells of the body where it is used to fuel the mitochondria. Erythropoesis, or manufacture of RBCs, takes place in the bone marrow. The RBCs are then transported to the bloodstream where they live for about 120 days in a healthy individual. Depressed hemoglobin levels can also cause anemia.

Generally speaking, most anemia has one of two broad causes:

  1. Decreased production of RBCs and/or hemoglobin
  2. Increased loss or destruction of RBCs, such as a bleeding disorder (1)

RBCs are the most abundant blood cell by far and make up 40-45% of the blood by volume. Even though RBCs live about four months, the body must manufacture an astonishing two million erythrocytes every second to keep up with the equally high rate of RBC destruction. The anatomy of RBCs is highly specialized to provide optimal oxygen transportation abilities.

Symptoms of anemia

Because depressed RBCs negatively affect the body’s ability to fuel its cells with oxygen, many of the symptoms of anemia revolve around difficulty supplying cells with enough oxygen such as low energy levels and shortness of breath.

Symptoms of anemia include: 

  • Fatigue
  • Weakness
  • Pale or yellowish skin
  • Irregular heartbeats
  • Shortness of breath
  • Dizziness or lightheadedness
  • Chest pain
  • Cold hands and feet
  • Headache (1)

Now that we know what anemia is and what the symptoms are, let’s look more in depth at how RBCs carry oxygen and get into more detail about the etiology of anemia, as well as different forms. One of the most important components of RBCs is hemoglobin, which is the iron-containing component of erythrocytes.

Hemoglobin & Iron

Each RBC contains about 280 million hemoglobin molecules and each hemoglobin molecule contains four heme, nonprotein pigments that contain iron ion (Fe2+) which are able to reversibly combine with oxygen molecules, making oxygen transport possible. Hemoglobin also transports about 23% of carbon dioxide, a metabolic waste product, for excretion (2).

Because the iron in hemoglobin binds oxygen for transport by RBCs, a deficiency of iron can lead to iron deficiency anemia, the most common form. We’ll talk about iron-deficiency more shortly. Now that we’ve reviewed relevant erythrocyte anatomy and physiology, let’s move on to the different forms of anemia.

Forms of anemia

Primary or secondary anemia can result from many different causes. In this section we’ll review some of the most common kinds.

Iron deficiency anemia

We touched on this form of anemia earlier. Iron is critical for the manufacture and proper function of RBCs. Iron deficiency primarily results from inadequate intake or absorption, excessive loss through bleeding, or increased iron demand, and it is the most common form of anemia. Individuals eating a strict vegetarian or vegan diet are among the most likely to have inadequate iron intake (3). Iron malabsorption is common with gastric ulcer, parasites, H. pylori infection (4), hypochlorhydria, and in digestive disorders like Crohn’s and celiac disease (5).

Increased iron loss is common in women with heavy menses and in cases of internal bleeding (6). The presence of blood in the stool, especially dried blood that resembles coffee grounds is a strong indication of intestinal bleeding. An occult blood test can also identify blood in the stool that is not visible. When diagnosing iron deficiency anemia, we include more serum markers than with some other forms of anemia, like megaloblastic anemia. An anemia panel for iron deficiency that we use in our clinic includes ferritin, serum iron, UIBC, transferrin saturation, and an CBC w/ differential (at a minimum for comprehensive diagnosis…we sometimes include other markers as well).

Megaloblastic anemia

Megaloblastic anemia is also known as “B12 deficiency anemia” because it is caused by a lack of vitamin B12 and/or folate. Both of these B vitamins are required for erythropoesis, or RBC synthesis. Pernicious anemia (PA) is a common cause of B12 deficiency and megaloblastic anemia, and results from an inability to produce intrinsic factor, which binds to B12 in the stomach and makes absorption in the small intestine possible. PA can also be autoimmune and is confirmed with a positive intrinsic factor antibody blood test. To learn more about megaloblastic anemia, refer back to our recent post on B12 injections.

As we discussed in that post, another common underlying cause of B12 deficiency is a strict vegetarian or vegan diet that does not include any fish or shellfish. Microalgae like spirulina are often believed to contain B12, but instead mostly contain B12 analogues that not only are inactive in the body, they actually block the absorption of usable B12! We don’t recommend spirulina for B12, as it can actually contribute to deficiency by blocking absorption of active B12 (7).

Another interesting aspect of megaloblastic anemia we have observed clinically is a relationship between Small Intestine Bacterial Overgrowth (SIBO) and megaloblastic anemia. It’s fairly well known that SIBO can push B12 low by preventing absorption, and it can also increase folate (8). Some of the SIBO bacteria produce folate, and what we have observed clinically is that sometimes after treating SIBO,  B12 comes back up and folate levels drop, so it can be worth retesting both of these B vitamins after treating SIBO in cases of anemia, as both can change significantly with successful SIBO treatment.

Anemia of chronic inflammation

This type of anemia is secondary to chronic inflammation and is initiated by the activation of inflammatory cytokines like interleuken-6 (IL-6). Anemia that presents with elevated inflammatory cytokines may indicate anemia secondary to inflammation. The spike in cytokines leads to inflammation by several mechanisms:

  • Increases hepatic production and secretion of hepcidin, a peptide which inhibits iron transport and absorption
  • Hepicidin also prevents the stores from being released and utilized
  • Suppresses erythroid precursor proliferation in the bone marrow
  • Inhibits erythropoietin from the kidney
  • Shortens lifespan of RBCs (9)

Chronic disease can also produce a similar type of anemia. Chronically increased WBC production to support an elevated immune response can come at the expense of RBC production and lead to decreased erythropoesis.

Hemolytic anemia

In hemolytic anemia, RBC plasma membranes rupture prematurely and release hemoglobin into the bloodstream. This can overload and damage the glomeruli units in the kidneys that filter blood. Hemolytic anemia can result from many different causes, including inherited defects like altered RBC enzymes, or from exogenous influences like parasites and toxins (10).

Thalassemia is a related group of hereditary hemolytic anemias, which are characterized by deficient synthesis of hemoglobin. In thalassemia, RBCs are small (microcytic), pale (hypochromic) and short-lived. We’ll get into terms for the size and color of RBCs shortly.

Sickle cell disease

Sickle cell anemia is characterized by misshapen RBCs that contain an abnormal kind of hemoglobin and as a result become long, sickle-shaped and unable to carry oxygen. As a result of their abnormal shape, sickle cells rupture easily and die prematurely, resulting in low RBCs. Sickle cells also clump together and can cause blockages in blood vessels (11).

Describing anemic RBCs

Different types of anemia are described in terms of the size and color of the RBCs.

  • Size: 
    • Large – macrocytic
    • Medium – normocytic
    • Small – microcytic
  • Color:
    • High – hyperchromic (or megaloblastic)
    • Medium – normochromic
    • Low – hypochromic

We can see how the types of anemia already discussed can fall into these categories:

  • Mirocytic hypochromic:
    • Iron deficiency
    • Anemia of blood loss
    • Anemia of chronic inflammation / disease
    • Thalassemia
  • Normocytic normochromic:
    • Anemia of chronic inflammation / disease
    • Anemia of acute blood loss
    • Hemolytic anemia
    • Sickle cell
  • Megaloblastic:
    • B12/folate deficiency
    • Pernicious anemia

These distinctions will come into play into the next section on lab testing. One primary way different types of anemia are distinguished from each other is by looking at color and size of the RBCs.

Lab testing for anemia

There are many anemia patterns, as anemia can have many different etiologies. These manifest differently on labwork. Anemia is primarily diagnosed through the RBC section of the Complete Blood Chemistry (CBC). We’ll go over those in this section, discuss some patterns and also a few other markers that can be useful to run.

Anemia in general is identified by depressed RBCs, hemoglobin (HGB) and hematocrit (HCT). From there we look first at Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Hemoglobin Concentration (MCHC) to begin to distinguish different types. Red Blood Cell Distribution Width (RDW) is also useful, especially when mixed anemia is present.

  • Anemia is defined as:                                                            ideal ranges
    • Low RBCs (below the following ideal range)           (M) 4.4-4.9         (F) 3.9-4.5
    • Low HGB (below the following ideal range)            (M) 14-15 g/dL   (F) 13.5-14.5 g/dL
    • Low HCT (below the following ideal range)            (M) 39-55%        (F) 37-44%
  • MCV looks at cell size:                   defined as
    • Depressed – microcytic          <80 fL
    • Normal – normocytic             80-100 fL
    • Elevated – macrocytic            >100 fL
  • MCH & MCHC look at cell color:            defined as
    • Depressed – hypochromic     MCH <85 pg          MCHC <32 g/dL
    • Normal – normochromic       MCH 85-92 pg      MCHC 32-36 g/dL
    • Elevated – hyperchromic       MCH >92 pg          MCHC >36 g/dL

Let’s look at these markers in a little more detail before moving on to other important anemia markers.

  • RBCs: the absolute number of cells per liter of blood, which if low may indicate deficient synthesis, increased destruction, or excessive blood loss. High RBCs are associated with high altitude, dehydration, bone marrow disorders or renal disorders.
  • Hemoglobin (HGB): The main iron-containing oxygen-transport metalloprotein in RBCs which carries oxygen to the cells and carbon dioxide to the lungs for expiration.
  • Hematocrit (HCT): A measurement of the RBC-containing fraction of whole blood.
  • Mean Corpuscular Volume (MCV): The average volume of an RBC, which is used to distinguish microcytic, normocytic and macrocytic anemia from each other.
  • Mean Corpuscular Hemoglobin (MCH): The average mass of hemoglobin per RBC.
  • Mean Corpuscular Hemoglobin Concentration (MCHC): The average concentration of hemoglobin in the cells. This is used to distinguish between hypochromic, normochromic and megaloblastic (hyperchromic) anemia.
  • Red Blood Cell Distribution Width (RDW): This is a measure of the variation in RBC size. High RDW may indicate a mixed anemia like concurrent microcytic and macrocytic or early stage anemia when there is more variation in the size of RBCs being produced.

Next, we’ll talk about how iron status can impact the presentation of anemia before talking about how to correctly identify and treat the root cause.

Iron markers and disorders

Because of the crucial role iron plays in oxygen transport and anemia, iron disorders overlap with anemia quite a bit. Iron analysis markers are useful in classifying some types of anemia and distinguishing anemia from non-anemia iron disorders. Iron is also essential for erythropoiesis (RBC creation) and DNA synthesis (12). Iron disorders are a large subject all on their own, which we may cover in a future post. We’ll just discuss iron here briefly as it relates to anemia.

Iron-deficiency anemia is a form of microcytic hypochromic anemia characterized by depressed ferritin, serum iron and iron saturation and elevated TIBC and transferrin. There can be many causes of iron-deficiency anemia, many of which involve either reduced iron intake or absorption, or increased blood loss, or both.

Common causes of iron-deficiency anemia:

  • Reduced iron intake:
    • Evaluate diet for iron intake, vegetarian/veganism
    • Heme iron vs non-heme iron
  • Reduced iron absorption:
    • H. pylori
    • Hypochlorhydria
    • Celiac disease
    • Parasites (hookworms, roundworms, pinworms)
  • Increased blood loss:
    • Gastric ulcer
    • Internal bleeding
    • Heavy menses
    • Occult blood in stool

One thing we often see in our office is vegetarians and vegans who are deficient in iron, despite making a concerted effort to eat iron-rich vegetable sources like spinach. Vegetable sources of iron contain non-heme iron, which must be converted into heme iron to be utilized in the body. In contrast, animal sources of iron are much higher in heme iron. One of the best sources is red meat. As we discussed in our previous post on B12 injections, plant foods do not contain B12. Consequently, strict vegans and vegetarians who do not eat any fish or shellfish are at increased risk of B12 deficiency, as well as iron deficiency.

Because iron status is such a large subject on its own, we will continue the iron discussion in a future post with information on iron overload, non-anemia iron deficiency and hereditary hemochromatosis. Now that we’ve covered some of the common markers, let’s emphasize focusing on root-cause diagnosis before putting it all together with some anemia patterns.

What’s the root cause?

As we have seen in many other cases, it’s critical to correctly identify the underlying root cause of anemia. For example, just within the category of iron deficiency anemia, it is important to identify if a person is anemic because of a yet undaignosed H. pylori infection, or the anemia could be secondary to heavy menses that are depleting iron. These are just two of many possible root causes of iron deficiency.

Lab testing to order

The markers we talked about earlier like RBCs, HCT, MCV, MCH, MCHC and RDW are all part of a standard CBC. That is a great starting point. Other important markers to consider are iron status markers like ferritin, serum iron, UIBC, and transferrin saturation if iron deficiency anemia is suspected. We will go into these more in our upcoming post on iron. If, on the other hand megaloblastic anemia is suspected, markers of B12 and folate status are important (such as serum B12, serum folate, RBC folate, homocysteine, Methylmalonic Acid (MMA), and possibly holotranscobalamin if available in your area. Pernicious anemia can be confirmed with a positive intrinsic factor antibody in cases of suspected pernicious anemia.

Getting started

Start with the RBC breakdown on the CBC to determine whether the anemia is micro-, normo- or macrocytic and hypo-, normo- or hyperchromic. Once you’ve identified the type, look at possible underlying causes and order further testing as appropriate, whether it’s a SIBO breath test, an iron panel, inflammatory cytokines or MMA and folate. Getting a serum B12, homocysteine, and ferritin value are also standard orders for nearly every patient in our clinic (on top of a CBC with differential).

If you are vegan or strictly vegetarian, you may need to supplement with vitamin B12, iron, zinc, and possibly other trace minerals (best to check and confirm deficiencies as excessive amounts of some nutrients like iron or zinc can be toxic. B12 is generally considered to be safe with low chances for toxicity even with excessive doses). Some people decide to become vegetarian or vegan for health reasons. While there are conditions that can improve from various diets, vegetarian and vegan diets included, there are times when the health benefits can be exaggerated or the negative health impacts can be ignored. An example is the “What the Health” documentary. This movie has been the subject of several of our patients who have inquired about whether they should be eliminating animal products from their diet.

Unfortunately, this movie does a great job of touching into peoples emotions, but is very poor in citing any well-done, peer-reviewed research (although some people watching it think that it must be valid evidence). It is our professional opinion that the research cited in this movie is of poor quality and that the perspective was biased without considering both sides of the issue. We do not generally recommend vegetarian or vegan diets for health reasons in most cases. However, we completely understand ethical / religious reasons for choosing these kinds of diets and support clients who consciously choose these kinds of diets with recommendations for how to avoid nutrient deficiencies (especially by supplementing with some of the nutrients listed above and choosing certain foods that are rich in nutrients that are commonly deficient). For pescatarians (or vegetarians that are comfortable eating things that do not have faces), clams are a fantastic source of vitamin B12 and iron (plus other minerals). Oysters are the highest source of zinc. Just one or two servings of clams per week can correct some of the nutrient deficiencies that are common in vegetarians / vegans who are willing to eat shellfish.

If you struggle with some or all of:

  • Fatigue
  • Weakness
  • Dizziness
  • Pale skin

Plus you have some of the risk factors like:

  • Vegan diet
  • Excessive bleeding
  • Gastrointestinal (gut) infections
  • Extreme exercise

It is worth getting lab testing from a functional medicine doctor who can assess for functional ranges and help identify the root cause(s) behind anemia or other conditions that can also cause some of the same kinds of symptoms.

Check back soon for our future posts which will expand this information. We’ll get more detailed about iron markers and other anemia patterns.


  1. National Institute on Health. “Anemia: Symptoms – National Library of Medicine – PubMed Health.” National Center for Biotechnology Information, U.S. National Library of Medicine,
  2. Tortora GJ. and Grabowski SR. (1993) Principles of Anatomy and Physiology. Harper Collins College Publishers.
  3. Pawlak R, Lester SE, Babatunde T. The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature. Eur J Clin Nutr. 2014;68(5):541-8.
  4. Ciacci C, Sabbatini F, Cavallaro R, et al. Helicobacter pylori impairs iron absorption in infected individuals. Dig Liver Dis. 2004;36(7):455-60.
  5. Saboor M, Zehra A, Qamar K, Moinuddin. Disorders associated with malabsorption of iron: A critical review. Pakistan Journal of Medical Sciences. 2015;31(6):1549-1553. doi:10.12669/pjms.316.8125.
  6. Moschonis G, Papandreou D, Mavrogianni C, et al. Association of Iron Depletion with Menstruation and Dietary Intake Indices in Pubertal Girls: The Healthy Growth Study. BioMed Research International. 2013;2013:423263. doi:10.1155/2013/423263.
  7. Watanabe F, Katsura H, Takenaka S, et al. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J Agric Food Chem. 1999;47(11):4736-41.
  8. Dukowicz AC, Lacy BE, Levine GM. Small Intestinal Bacterial Overgrowth: A Comprehensive Review. Gastroenterology & Hepatology. 2007;3(2):112-122.
  9. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. Journal of Clinical Investigation. 2004;113(9):1271-1276. doi:10.1172/JCI200420945.
  10. Dhaliwal G, Cornett PA, Tierney LM. Hemolytic anemia. Am Fam Physician. 2004;69(11):2599-606.
  11. Dubert M, Elion J, Tolo A, et al. Degree of anemia, indirect markers of hemolysis, and vascular complications of sickle cell disease in Africa. Blood. 2017;130(20):2215-2223.
  12. Wu CJ, Krishnamurti L, Kutok JL, et al. Evidence for ineffective erythropoiesis in severe sickle cell disease. Blood. 2005;106(10):3639-3645. doi:10.1182/blood-2005-04-1376.
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December 11, 2017

Does Acupuncture Really Work? Researched Benefits of Acupuncture

Benefits of Acupuncture

by Aaron Mello, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

Acupuncture is a treatment that has been used in China for thousands of years. More recently, the practice has become popular in the United States and other Western countries. Despite its long history of use, acupuncture has only begun to be formally researched in the last few decades. Only in the last 10-20 years have researchers begun conducting more rigorous, quality trials to evaluate the benefits of acupuncture. That being said, clearly acupuncture has withstood the test of time and is one of the oldest forms of medicine that has withstood the test of time and remains an important part of medicine not only in China, but all over the world. In addition to research, it is important to also consider longevity of a system because those systems that become outdated and do not work tend to fade away at least out of larger medical systems. The test of time clearly shows that acupuncture is safe and popular. In this blog, we will explore whether it is also proven to be effective from a research-based perspective.

In this blog post we will change gears a bit from some recent posts on herbs and nutraceuticals and review the research and see what benefits of acupuncture are supported by well performed research. Lately we’ve been writing about B12 injections, pyroluria, multitasking and heart health. Acupuncture is a powerful complementary modality that works on an energetic level which can work synergistically with other “physical” approaches like nutrition and herbal remedies.

Acupuncture is effective for a wide range of conditions. In this article we will review research on the benefits of acupuncture for insomnia, neck pain, migraine, low back pain, chronic pain and depression. There are many other conditions acupuncture is used to treat. We use acupuncture extensively in our office. Dr. Diane Mueller, Dr. Miles Nichols, and Dr. Melati Olivia (docs in our clinic) are all Doctors of Acupuncture and Oriental Medicine (in addition to functional medicine). We’re excited that new, better performed research is being performed to bring more understanding to the ancient practice of acupuncture!

A brief history of acupuncture

Acupuncture probably originated in China, possibly as long ago as 6000 BCE – about 8000 years ago. The first known document that describes a system of diagnosis and treatment is the The Yellow Emperor’s Classic of Internal Medicine, which dates back to about 100 BCE. It describes the concept of energy meridians through which Qi flows, a concept which is still found in modern acupuncture. Since that time, acupuncture has continued to evolve.

By the time of the Ming Dynasty (1368 – 1644 AD) these concepts had been consolidated into The Great Compendium of Acupuncture and Moxibustion. This text forms the basis of modern acupuncture. In the 19th century, interest in acupuncture declined and it was outlawed for about 20 years in 1929 on the grounds that it was superstitious. Acupuncture came back into favor when the Communist government rose to power in 1949, and divergent strands of acupuncture and herbal medicine were combined into Traditional Chinese Medicine (TCM), which is how it is known today (1).

How acupuncture works

Acupuncture treatment involves the stimulation of “acupuncture points” with very thin needles which are found along energy meridians in the body. As such, it is an energy-based practice. The TCM philosophy of health revolves around the relationship between Yin and Yang, and Qi and blood. Qi is life force. Without Qi, there would be no life. Qi infusing all living things. Yang represents the active, ascending, subtle, expansive pole of Qi. Yin represents the nurturing, receptive, earthly, restful pole of Qi. Blood is said to be yin and nourishing in nature, serving the function to nourish the cells of the body. Diseases develop when Yin and Yang become out of balance. When this happens, Qi and blood become stagnant and do not flow properly.

The benefits of acupuncture result from balancing energy in the body through the stimulation of acupuncture points, which correspond to major organs of the body. The points are selected by a qualified practitioner after making a diagnosis and treatment strategy. Some Western practitioners propose a different mechanism of action and suggest that acupuncture works by stimulating nerves, muscles and connective tissue, which may in turn increase blood flow and the release of natural endorphins. Regardless of the mechanism, we will be focused mostly on exploring the benefits that research supports from the procedure of acupuncture.

Safety of acupuncture

Acupuncture is generally very safe. The main risks are usually minor and include infection, bleeding, hematoma, pain, and mild bruising. One large German study looked at the incidence of adverse reactions in a cohort of almost 230,000 patients who received an average of about 10 treatments each. In all, 8.6% of patients reported an adverse event and 2.2% of those required treatment (2). Compared to the risks associated with many medications and surgical procedures, acupuncture appears quite safe.

Another large study, this one in Britain, evaluated the number of adverse events in a pool of 34,407 treatments over a four week period. Practitioners were asked to report incidents they considered to be significant, defined as “unusual, novel, dangerous, significantly inconvenient, or requiring further information.” There were no serious adverse events requiring hospital admission, leading to permanent disability or death. A small number of cases, less than 2% reported mild bruising, pain and bleeding at the site of needle placement (3).

The safety of acupuncture is considered to be significant enough for it to be common practice to use acupuncture with women who are pregnant. This is incredibly important because there are many medications and other procedures that have not been shown to be safe during pregnancy. Acupuncture may be one of the best choices for pregnant women to receive relief from pain or other problems that arise during pregnancy. Acupuncture has been time tested with a long history of safe use with pregnancy.

Research is difficult

The benefits of acupuncture are somewhat difficult to study accurately. One main problem is that, unlike many drug and nutritional supplement studies, placebos are difficult to utilize. Patients can easily tell whether a needle is inserted or not, so many studies that attempt to use a placebo utilize what is called “sham acupuncture,” which usually involves needling points that are either not known acupuncture points or points that are unrelated to the condition being treated. Some research has found that “true acupuncture” is no more effective than “sham acupuncture,” which may suggest that the placebo effect may account for most, if not all of the benefit (4).

However, this research is actually doing acupuncture despite trying to look for a placebo effect. In truth, non-meridian points that are used in studies are used in the practice of acupuncture also (acupuncturists will use what are called “ashi” points to needle any area of the body that is painful or might benefit the person). Thus, the argument that acupuncture is ineffective because you can needle non-meridian points to get a similar effect is actually really implicating that acupuncture is effective, just that staying on meridians may not be necessary for that benefit.

Another difficulty is that a double blind structure is nearly impossible to achieve. The acupuncturist administering treatment will know whether the points s/he is needling are valid or “non points,” making bias hard to avoid. It is possible for the treatment to be designed and administered by different acupuncturists if using points irrelevant to the patient’s symptoms or disease. But in this case, there may still be some benefit or effect from needling active points, even if they do not appear to relate directly to a patient’s symptoms or disease etiology. Furthermore, a treatment plan of randomly placed acupuncture points that do not form a coherent treatment would be obvious to most trained acupuncturists, affecting bias.

In addition, acupuncturists are trained to use unique point combinations for each individual (not the same set of points for different people that have the same condition). Much of the research requires needling the same set of points for different people with the same condition which goes against acupuncture training (because there might be several different reasons why a condition arose from acupuncture theory). This makes it difficult to evaluate whether acupuncture for a given condition is effective, as different acupuncturists may be using different approaches and even the same acupuncturist will use a different treatment plan for different patients with the same condition. We of course know that even in Western medicine, similar symptoms may result from much different causes.

Finally, in addition to the above issues, much of the research has been of low quality. There is not an abundance of funding for such research because there are not potential drugs to patent that may result from the research. Consequently, many trials on the benefits of acupuncture have not been well constructed and are subject to bias. With all that being said, there have been some better constructed trials in recent years. This is clearly evidenced by the US Army’s use of acupuncture for pain relief (with significantly lower pain medication use from injured soldiers using acupuncture). Let’s go on next to review the research we do have.

Benefits of acupuncture

In this section we’ll review research which has demonstrated significant benefits of acupuncture for various conditions. We’ll include conditions, symptoms and diseases that are the best researched and focus on meta-analyses, which each include many studies, and often thousands of participants. Meta-analyses are considered the gold standard of research because in addition to including a large sample size, they typically exclude poorly designed studies. We also focus on studies that have a sham acupuncture group because blinding is not possible in research that compares acupuncture to no treatment. In the next section we’ll go through the research we found for each disease or condition.


One fairly large meta-analysis of 46 randomized trails comprising 3811 patients compared the benefits of acupuncture to no treatment, sham acupuncture and sleeping medication. The acupuncture showed a beneficial effect of acupuncture as compared to both no treatment and sham acupuncture. In addition, acupuncture was superior to medications for increasing sleep duration for more than three hours, and provided comparable increases in average sleep duration. Acupuncture plus medication was also superior to medication alone, and no serious adverse effects resulted from acupuncture in the included trials (5).

Neck pain

We found another large meta analysis which included about 10,000 participants with various types of neck pain. The most common conditions evaluated were subacute or chronic neck pain and chronic non-specific neck pain. Researchers evaluated the benefits on several metrics and found that compared to sham acupuncture, real acupuncture was beneficial for reducing pain intensity and disability. This study only looked at short-term outcomes and did not evaluate whether repeated sessions would be successful. This study echoed the safety of the previous one on insomnia and found that adverse were minor, adding also that the treatments were cost-effective (6).


A 2016 Cochrane review paper evaluated 22 trials including almost 5000 participants who suffer from migraine and compared acupuncture to no treatment, sham acupuncture and prophylactic drug treatment. Compared to no treatment, acupuncture was associated with a moderate reduction of headache frequency. Compared to sham acupuncture, acupuncture resulted in a small by statistically significant reduction in frequency of headaches. And in the final category, acupuncture reduced migraine frequency significantly more than drug treatment after treatment, but this did not continue at the follow-up session. All the same, the acupuncture groups reported small but significant reductions in headache frequency at three and six months, as compared to the drug treatment groups.

Regarding safety, this meta-analysis on the benefits of acupuncture for migraines also found adverse effects of be rare. The number of adverse effects did not differ significantly between the real acupuncture and sham acupuncture groups. And in the drug treatment comparison groups, acupuncture treatment participants were less likely to report adverse effects and less likely to drop out due to them. The authors conclude that acupuncture results in a small but significant reduction in frequency of migraine headaches compared to sham acupuncture, and that acupuncture may be at least similarly effective to drug treatment (7).

Low back pain

Low back pain is an extremely common problem that most people experience at some point during their life (8). It represents a major problem that is often treated with opiate painkillers, which can lead to addiction over time. The research on the benefits of acupuncture for low back pain is somewhat mixed and many studies cite the prevalence of low quality research. One meta-analysis of 11 RCTs compared acupuncture to NSAIDs and found that “acupuncture may more effectively improve symptoms of acute LBP.” Researchers also noted that acupuncture was more effective at reducing pain than sham acupuncture (8).

Another meta-analysis of 33 RCTs found that acupuncture was significantly more effective than sham treatment at providing short-term relief of chronic back pain (10). Both this study and another found move evidence to support acupuncture for chronic lower back pain than acute (9). Several of the studies cited conflicting results in some cases and an overall low quality of evidence. Hopefully future research will clarify this issue for us.

Chronic pain

The benefits of acupuncture for the treatment of chronic pain is fairly well established. A large JAMA meta-analysis of 29 RCTs comprised of almost 18,000 participants evaluated the effects of acupuncture on four categories of chronic pain – back and neck pain, osteoarthritis, chronic headache and shoulder pain. They found acupuncture to be “superior to both shame and no-acupuncture control for each pain condition.” The effect sizes were similar across all pain conditions. The authors note that although the differences were relatively modest, there was a significant difference between real and sham acupuncture, indicating a clear effect in addition to placebo (10).


Acupuncture also appears to improve symptoms of depression, and may also reduce side effects of antidepressant medications. One review found that acupuncture is a generally beneficial, well-tolerated and safe way to treat depression (11). Some other studies find conflicting results and have concluded that acupuncture does not provide a clear benefit over sham acupuncture. As an example, a large Cochrane review study failed to find a consistent beneficial effect of acupuncture as compared to sham acupuncture or a wait list.

Interestingly, the authors also noted that most of the included trails found no benefit between acupuncture and antidepressant medication (12). The authors do not appear to attempt to reconcile how medication, an accepted primary treatment for depression, did not differ in efficacy from acupuncture, which they conclude lacks sufficient evidence to support its clinical application. Other research has found that as much as 80% of the benefit of SSRI antidepressants results from the placebo effect (13).

When it comes to depression, the evidence is mixed. Some studies pointed out that depression is hard to treat in general, and that recurrence of symptoms is common. We have had good luck treating depression in our office with acupuncture especially by focusing on a root-cause evaluation. We often think of depression as being a symptom of an upstream root cause and work to identify and treat whatever is leading to the depression.

In conclusion

Research on the benefits of acupuncture is limited and somewhat difficult to perform in a double-blind placebo-controlled manner, which is the gold standard for research at this point. There is a moderate body of research at this point to support the use of acupuncture for the treatment of insomnia, neck pain, migraine, low back pain, chronic pain and depression. It is our hope that more well-devised research studies will continue to illuminate the conditions acupuncture is effective in treating, and provide more detail on which modalities and treatment approaches are the most effective for a given affliction or condition.

Does this mean that acupuncture isn’t good for digestive issues, fatigue, menstrual problems, or infertility? Absolutely not! Lack of ample quality research is not evidence against effectiveness. There are plenty of subjective reports of success with these and more issues. Whether acupuncture helps in a significant way on average for most people remains to be seen. There is some limited research for some of these conditions with positive implications. More research is needed, though, to draw stronger conclusions.

One thing is clear: acupuncture has withstood the test of time and is generally regarded as very safe. For those with conditions not responding to other treatments, acupuncture may be worth a go.


  1. A. White, E. Ernst; A brief history of acupuncture, Rheumatology, Volume 43, Issue 5, 1 May 2004, Pages 662–663,
  2. Witt, Claudia M., et al. “Safety of Acupuncture: Results of a Prospective Observational Study with 229,230 Patients and Introduction of a Medical Information and Consent Form.”Complementary Medicine Research, vol. 16, no. 2, 2009, pp. 91–97., doi:10.1159/000209315.
  3. Macpherson, H., et al. “The York Acupuncture Safety Study: Prospective Survey of 34 000 Treatments by Traditional Acupuncturists.” British Medical Journal, vol. 323, no. 7311, Jan. 2001, pp. 486–487., doi:10.1136/bmj.323.7311.486.
  4. Moffet, Howard H. “Sham Acupuncture May Be as Efficacious as True Acupuncture: A Systematic Review of Clinical Trials.” The Journal of Alternative and Complementary Medicine, vol. 15, no. 3, 2009, pp. 213–216., doi:10.1089/acm.2008.0356.
  5. Cao H, Pan X, Li H, Liu J. Acupuncture for Treatment of Insomnia: A Systematic Review of Randomized Controlled Trials. Journal of Alternative and Complementary Medicine. 2009;15(11):1171-1186. doi:10.1089/acm.2009.0041.
  6. Trinh, Kien, et al. “Acupuncture for Neck Disorders.” Cochrane Database of Systematic Reviews, Apr. 2016, doi:10.1002/14651858.cd004870.pub4.
  7. Linde, Klaus, et al. “Acupuncture for the Prevention of Episodic Migraine.” Cochrane Database of Systematic Reviews, 2016, doi:10.1002/14651858.cd001218.pub3.
  8. Lee, Jun-Hwan, et al. “Acupuncture for Acute Low Back Pain.” The Clinical Journal of Pain, vol. 29, no. 2, 2013, pp. 172–185., doi:10.1097/ajp.0b013e31824909f9.
  9. Liu L, Skinner M, McDonough S, Mabire L, Baxter GD. Acupuncture for Low Back Pain: An Overview of Systematic Reviews. Evidence-based Complementary and Alternative Medicine : eCAM. 2015;2015:328196. doi:10.1155/2015/328196.
  10. Vickers, Andrew J., et al. “Acupuncture for Chronic Pain.” Archives of Internal Medicine, vol. 172, no. 19, 2012, p. 1444., doi:10.1001/archinternmed.2012.3654.
  11. Wu, Junmei, et al. “Acupuncture for Depression: A Review of Clinical Applications.” The Canadian Journal of Psychiatry, vol. 57, no. 7, 2012, pp. 397–405., doi:10.1177/070674371205700702.
  12. Smith, Caroline A, et al. “Acupuncture for Depression.” Cochrane Database of Systematic Reviews, 2010, doi:10.1002/14651858.cd004046.pub3.
  13. Kirsch, Irving. “The Emperor’s New Drugs: Medication and Placebo in the Treatment of Depression.” Placebo Handbook of Experimental Pharmacology, 2014, pp. 291–303., doi:10.1007/978-3-662-44519-8_16.


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December 11, 2017

10 Recommendations to Maintain Gut Health this Holiday Season

holidays gut health

holidays gut health

It’s no secret that a lot of people let their health habits slip during the holidays. We understand the excitement, stress, and time constraints of this season: Sometimes it’s hard to put your gut health at the forefront. But, neglecting your gut health during the holidays is not a good gift to give yourself. Here are 10 recommendations on how to focus on gut health during the holidays:

1) Continue eating prebiotic foods. Everyone talks about probiotics. Probiotics are important yes, but they cannot survive unless we feed them. The food for the healthy bacteria in our body are called prebiotics. Foods that are prebiotics include lentils, dandelion greens, green bananas, green plantains, onions (can be cooked, but need to still be crunchy), and potatoes (must be cooked and cooled for 24 hours and eaten cold).

2) Pick “treat” days around the holidays. The holidays are a time for a little extra indulgence. In health, our bodies can handle some indulgences. The trouble lies where we start having indulgences on a regular basis. So look at your calendar, pick 1-2 days/week and designate them treat days. Participate in treats on these days and say no the rest of the time. It will help both your gut AND your waist line!

3) Zinc Carnosine: Zinc carnosine is a form of zinc that helps to heal the gut lining and keep the intestinal cells happy.

4) Alcohol: Womens can pretty safely detox one drink/day and men can detox two. Any more than this can impact the health of the gut and can contribute to leaky gut. Therefore, make it your holiday goal not to have more than these recommendations.

5) Since sugar is an unavoidable part of the holiday season, pick healthy sugars. If you are going to a party, make a paleo version of a recipe. Or substitute cookies with buckwheat flour and coconut sugar for healthier versions.

6) Gluten is another food that is hard to avoid around the holidays. Gluten causes leaky gut EVEN in those who are not sensitive or allergic. Therefore, we should all minimize or eliminate gluten even if we do not notice it. Substitute buckwheat flour, cassava flour, coconut flour or other gluten free flours for wheat. The website Paleo Mom has great recipes.

7) No matter how much we plan in advance, the holidays can be stressful. So much family, parties and traveling on top of our normal life activities leave many people pretty exhausted. Make a point to take 10 minutes for yourself every day to practice meditation or a mindfulness based stress activity. UCLA has great free guided meditations that can be found here: Put it in your calendar so that you remember!

8) Take an adrenal based product to help with stress around the holidays. See your functional medicine practitioner to know which adrenal product is right for your unique health condition.

9) Make a point to not sacrifice sleep. Work to make things simpler on yourself such as online shopping to help save time. Ask each family member to make one dish at the holiday season to decrease the work load. Be okay if the house is not as clean as you want. Sleep is your best friend to maintaining healthy weight, lower stress levels and a reduced waist line (yes, sleep deprivation is associated with diabetes and weight gain).

10) Plan a detoxification for after the holidays. There are three phases of gut detoxification. While most people think of the liver for detoxification, one of these phases exists largely in the small intestine. What does this mean? Your intestine is a detox organ! While the holidays are not a great time to detox, they are a great time to plan to start a detox afterwards to allow the body to heal. At Living Love, we offer easy to follow (non starvation) detox programs.

We work with people all around the country for these! Email for more information and receive a 10% discount if you sign up before December 21st.

Book a 15-min Discovery Phone Call!


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November 20, 2017

Got Enough B12? Benefits of B12 Injections

B12 Injections

by Aaron Mello, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

Vitamin B12 is an essential nutrient that is involved in many crucial functions in the body, and B12 injections are a great way to increase your levels. Do you know if you have enough B12? Consequences of B12 deficiency range from fatigue, vision loss and constipation to neurological problems, psychiatric problems and certain types of anemia. Vitamin B12 is found almost exclusively in animal foods, so long-term vegans and vegetarians are at an elevated risk of deficiency. In addition, absorption of this nutrient from food is a somewhat complex process and may be impaired in some people.

In this blog we’ll review the most important functions of Vitamin B12 in the body, which foods are good sources, what conditions and medications interfere with absorption, how to test for Vitamin B12 deficiency and the researched benefits of B12 injections. Because B12 absorption can be impaired even if you’re eating enough, you may be deficient even if you’re eating B12-rich foods. If you’re deficient in B12 despite eating good food, B12 injections are the most effective way to raise B12 levels. Keep reading to learn about the benefits of B12 injections!

Vitamin B12

Also known as cobalamin, vitamin B12 is an essential water-soluble nutrient that is part of the B complex of vitamins. B12 is more complex than the other B vitamins. The name cobalamin comes from the fact that this vitamin contains cobalt. B12 is the only B vitamin which contains this element. Different forms of cobalamin are available in supplement form, including cyanacobalamin, methylcobalamin, and hydroxocobalamin. Different forms of B12 injections are appropriate depending on an individual’s methylation status. Next, we’ll look at the roles B12 plays in the body.

Functions of vitamin B12

Vitamin B12 is required for many functions in the body. People who get B12 injections often cite increased energy as a primary benefit. One main way B12 improves energy levels is its role in the production of erythrocytes (red blood cells), which carry oxygen to the cells, where it is used to fuel energy-producing mitochondria. B12 deficiency leads to a type of anemia called megaloblastic anemia, which is characterized by depressed numbers of erythrocytes that are also immature and large, or macrocytic. Low levels of erythrocytes impair the body’s ability to supply cells with sufficient oxygen, resulting in anemic fatigue.

In addition to helping synthesize erythrocytes, Vitamin B12 is also used for:

  • DNA synthesis
  • Converting homocysteine to methionine
  • Neurotransmitter function
  • Synthesis of hormones
  • Producing the myelin sheath that coats nerves
  • Fetal development during pregnancy (1)

These are just some of the most important known functions of B12 and is certainly not an exhaustive list. Now that we know some of the critical functions of B12 in the body, let’s go on to symptoms of B12 deficiency before getting into the benefits of B12 injections.

Signs and symptoms of B12 deficiency

Because B12 is used for so many processes in the body, there can be many signs and symptoms. Because symptoms can have overlapping causes, these should not be used to diagnose B12 deficiency. With that said, these signs and symptoms may indicate that B12 testing is appropriate.

Here are the main signs and symptoms:

  • Pale or jaundiced skin
  • Weakness and fatigue
  • Peripheral sensation of “pins and needles” in extremities
  • Unsteady gait or trouble balancing
  • Glossitis – red, smooth and swollen tongue
  • Breathlessness or dizziness
  • Disturbed vision
  • Depression and other mood changes

Next, we’ll look at which foods are high in B12.

Food sources of vitamin B12

Vitamin B12 is primarily found in animal foods, so long-term vegans may be at increased risk for B12 deficiency if they are not supplementing or getting B12 injections. One review of 40 studies found that up to 86% of vegans may be deficient in B12 (2). Vegans with low B12 levels may want to consider whether their diet is still serving them. Omnivores may also be deficient, usually due to impaired ability to absorb B12 known as pernicious anemia, which we’ll discuss shortly. We’ll also get into testing to establish whether your B12 levels are adequate.

These foods are best sources of B12:

  • Clam
  • Grass-fed beef liver
  • Sardines
  • Salmon
  • Cod
  • Lamb
  • Oyster
  • Mussels
  • Scallops
  • Shrimp
  • Beef
  • Yogurt
  • Eggs

As you can see, these are all animal and marine sources. The best sources for vegetarians who eat seafood (pescetarians) are shellfish (especially clam), fish like sardines and salmon, eggs and yogurt. Some mushrooms also contain some B12, although it’s disputed whether the amount is significant (3). The same is true for fermented food like tempeh – the bacteria which ferment soybean into tempeh synthesize some B12, but it may be a form that has low affinity for intrinsic factor and is not well absorbed (4).

Consequently, supplementation is especially important for strict vegans. For most people, B12 injections are the best option to raise their B12 levels, whether they vegan, omnivorous or somewhere in the middle. This form bypasses the digestive tract and any problems that may prevent absorption. We’ll talk about absorption problems in the next section.

Inability to absorb B12

Many factors can result in an impaired ability to absorb B12 from food. In contrast to other B vitamins, B12 is more complex and absorption of this nutrient is more complicated. The parietal cells in the stomach secrete hydrochloric stomach acid (hcl) as well as intrinsic factor, which is required to absorb B12. Intrinsic factor binds to B12 and enables its absorption in the small intestine. B12 absorption relies on both intrinsic factor and adequate hcl. Many of the causes of B12 malabsorption are related to impaired hcl and intrinsic factor production.

Some of the most common causes of impaired B12 absorption are:

  • Pernicious anemia – more on this shortly
  • Parasitic infections like fish tapeworm and Giardia lamblia
  • Small Intestine Bacterial Overgrowth (SIBO)
  • Familial factors
  • Hypochlorhydria (low stomach acid)
  • Aging – stomach acid production declines with age
  • Gastrointestinal surgery that removes significant sections of the terminal ileum
  • Digestive disorders like Crohn’s disease or celiac disease
  • Certain medications like oral contraceptives, Metformin, proton pump inhibitors (PPIs) and others (5)

If a person is consuming a reasonable about of B12-rich foods in the diet but B12 levels are still low, this may indicate an issue with B12 absorption. In these cases, oral B12 supplements are unlikely to make much of an impact, as they too must be absorbed in the small intestine. These cases are especially good candidates for B12 injections, since that route of administration bypasses the digestive tract.

If a person is unable to absorb B12, it’s important to treat the root cause for that malabsorption. B12 shots bring levels of this crucial nutrient back up, but they do not resolve the underlying root cause. A B12 deficiency in an individual who’s eating B12-rich foods provides valuable information to indicate an underlying problem. It’s important to work with a qualified functional medicine practitioner to not just correct B12 levels with B12 injections, but also treat the underlying root cause. We’ll go into B12 malabsorption in the next section.

Pernicious anemia

Pernicious anemia (PA) is also known as B12 deficiency anemia, and occurs when the body is unable to absorb B12. We’ve already talked about the role of B12 in anemia and problems with absorption. Pernicious anemia is a common cause of B12 malabsorption and accounts for 20-50% of B12 deficiency in adults. It usually results from an autoimmune attack against either gastric parietal cells which secrete intrinsic factor and hydrochloric acid, or intrinsic factor itself. PA is diagnosed by testing for antibodies against intrinsic factor and/or gastric parietal cells (GPC) (6).

Pernicious anemia was identified in 1855 by Thomas Addison, the English physician best known in the context of Addison’s disease. At that point, PA was often fatal until science discovered that it was a B12 deficiency, hence the name pernicious, which means highly destructive or fatal. Even once the B12 connection was made it was still difficult to treat, as many people with PA are not able to absorb oral B12 supplements or foods high in B12 like liver (7). Happily, today it is easily treated with B12 injections, which bypass the digestive tract.

PA causes a type of anemia known as megaloblastic anemia, which we mentioned briefly earlier. Megaloblastic anemia is a form of macrocytic anemia characterized by large, oversized and immature erythrocytes paired with low overall levels of erythrocytes. Because B12 is required for proper maturation of erythrocytes, a deficiency of this vitamin results in pernicious anemia. Now that we understand the role B12 plays in PA, let’s go on to testing for B12 deficiency.

Testing for B12 deficiency

We use a blood test to diagnose B12 deficiency. In addition to getting serum B12 levels, we also run methylmalonic acid (MMA), which helps to provide more accurate results. The combination of these two markers provides the most accurate picture of B12 levels. MMA is inversely correlated with B12 levels and high MMA levels indicate a B12 deficiency and a need for B12 injections.

B12 is the only cofactor that metabolizes MMA into succinyl-CoA. Consequently, elevated MMA levels indicate there is not enough B12 to make the conversion to succinyl-CoA. MMA is considered a superior marker to serum B12 because that value can change fairly rapidly if B12 has been ingested recently, so B12 by itself can change quickly and be misleading. We like to run both B12 and MMA levels.

Another marker that is useful but not commonly available from US labs is holotranscobalamin II. This marker can detect even early stages of B12 deficiency (stage I and II). MMA detects middle stages, and serum B12 detects later stages. For a functional range on the most common test, we like to see serum B12 at least at 400 pg/ml (evidenced by research and supported in lab ranges in some countries like Japan). We optimally prefer to see 500 pg/ml or higher.

High homocysteine can be an indirect marker / indicator of B12 deficiency. It is also possible that homocysteine can be elevated with low folate or low B6 also. So it is not a guarantee of just B12 since there are other nutrients that can be depleted causing elevated homocysteine levels.

Benefits of B12 injections

If you are deficient in vitamin B12, injections are the most effective way to bring levels back up and alleviate a lot of symptoms. In this section we’ll explain some of the most common benefits.

  • Reduce fatigue:
    • Low B12 levels inhibits production of erythrocytes (red blood cells) and leads to fatigue. Bringing B12 levels back up through injection can significantly improve energy levels.
  • Improve athletic performance:
    • Exercise increases the body’s oxygen needs to fuel the mitochondria. Because B12 deficiency leads to anemia (low erythrocytes) and a reduced ability to carry oxygen to the mitochondria, athletic performance suffers. Bringing B12 levels back up can help improve oxygenation of mitochondria, and as a result, boost athletic performance.
  • Protects the heart by lowering homocysteine:
    • Homocysteine is a recognized risk factor for heart disease. One primary way to reduce homocysteine levels is through a B12-dependent pathway. (8)
    • See also our other recent posts about hawthorn, dan shen and pomegranate, which all support heart health.
  • Prevent cognitive decline associated with dementia:
    • High homocysteine is a risk factor for dementia in addition to heart disease and B12 can lower homocysteine. The benefits directly related to dementia may be limited to those with pernicious anemia who are unable to absorb B12 (9).
  • Reduce symptoms of depression:
    • Depressed patients often have low levels of B12. In addition, B12 and folate are required for S-adenyl methionine (SAMe) production, which donates methyl group that are crucial for proper neurological function (10).
    • We recently wrote about pyroluria, a condition that can cause symptoms of depression, as well as how omega-3s can impact pyroluria.
  • Improve hair, skin and nails:
    • B12 isn’t just used to produce erythrocytes, it’s required for multiple rapidly dividing cell lines including hair, skin and nails. In fact, one common symptoms of B12 deficiency anemia is brittle fingernails (11).
  • Increase sperm count and motility:
    • Vitamin B12 improves semen quality, increases sperm count and improves sperm motility. These benefits probably result from increased reproductive organ functionality, decreased homocysteine toxicity, reduced nitric oxide and reducing oxidative damage to sperm (12).
  • Reduces fetal development problems:
    • B12 is required for proper fetal development and deficiency has been linked to cognitive, motor and growth problems in fetal development (13).
  • Improve B12 deficiency symptoms:
    • We listed symptoms of deficiency earlier, including: Pale or jaundiced skin, weakness and fatigue, peripheral sensation of “pins and needles,” unsteady gait or trouble balancing, glossitis, breathlessness or dizziness and disturbed vision. These all stand to improve after correcting low B12 levels.

In summary

Vitamin B12 is a critical nutrient for many processes in the body, and deficiency can have serious consequences. Some effects of B12 deficiency can result in permanent damage, such as irreversible nerve damage. If you suspect that you may be deficient, it’s important to work with a qualified functional medicine practitioner to properly diagnose the deficiency, correct it with B12 injections and identify what underlying root cause is contributing to the deficiency.

When considering the value of increasing B12 levels:

  • Functional lab testing for serum B12, MMA, Homocysteine, and if possible Holotranscobalamin II can help identify a deficiency
  • Look at dietary sources and for vegans or vegetarians who are willing to have some shellfish, consider a weekly serving or two of clam
  • Consider B12 injections and/or supplementation if there is an absorption issue or if there is a medication being used that is depleting levels
  • Look for methylcobalamin or hydroxocobalamin for supplements and/or injections and avoid cyanocobalamin because of trace amounts of cyanide present in cyanocobalamin
  • Work with a functional medicine practitioner to find underlying root causes for why B12 levels are not sufficient and correct the root causes


  1. Black MM. Effects of vitamin B12 and folate deficiency on brain development in children. Food and nutrition bulletin. 2008;29(2 Suppl):S126-S131.
  2. Pawlak, R, et al. “The Prevalence of Cobalamin Deficiency among Vegetarians Assessed by Serum Vitamin B12: a Review of Literature.” European Journal of Clinical Nutrition, vol. 68, no. 5, 2014, pp. 541–548., doi:10.1038/ejcn.2014.46.
  3. Watanabe F, Yabuta Y, Bito T, Teng F. Vitamin B12-Containing Plant Food Sources for Vegetarians. Nutrients. 2014;6(5):1861-1873. doi:10.3390/nu6051861.
  4. O’Leary F, Samman S. Vitamin B12 in Health and Disease. Nutrients. 2010;2(3):299-316. doi:10.3390/nu2030299.
  5. Office of Dietary Supplements. “Vitamin B12.” NIH Office of Dietary Supplements, U.S. Department of Health and Human Services, 24 June 2011,
  6. Andres E, Serraj K. Optimal management of pernicious anemia. Journal of Blood Medicine. 2012;3:97-103. doi:10.2147/JBM.S25620.
  7. Chanarin, I. (2000), A history of pernicious anaemia. British Journal of Haematology, 111: 407–415. doi:10.1111/j.1365-2141.2000.02238.x
  8. Verhoef, P., et al. “Homocysteine Metabolism and Risk of Myocardial Infarction: Relation with Vitamins B6, B12, and Folate.” American Journal of Epidemiology, vol. 143, no. 9, Jan. 1996, pp. 845–859., doi:10.1093/oxfordjournals.aje.a008828.
  9. Werder SF. Cobalamin deficiency, hyperhomocysteinemia, and dementia. Neuropsychiatric Disease and Treatment. 2010;6:159-195.
  10. Coppen, Alec, and Christina Bolander-Gouaille. “Treatment of Depression: Time to Consider Folic Acid and Vitamin B12.” Journal of Psychopharmacology, vol. 19, no. 1, 2005, pp. 59–65., doi:10.1177/0269881105048899.
  11. Brescoll, Jennifer, and Steven Daveluy. “A Review of Vitamin B12 in Dermatology.” American Journal of Clinical Dermatology, vol. 16, no. 1, June 2015, pp. 27–33., doi:10.1007/s40257-014-0107-3.
  12. Banihani SA. Vitamin B12 and Semen Quality. Bähler J, ed. Biomolecules. 2017;7(2):42. doi:10.3390/biom7020042.
  13. Pepper, M. Reese, and Maureen M. Black. “B12 In Fetal Development.” Seminars in Cell & Developmental Biology, vol. 22, no. 6, 2011, pp. 619–623., doi:10.1016/j.semcdb.2011.05.005.
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November 18, 2017

The Pyroluria & Omega-3 Paradox

omega-3 & pyroluria

by Aaron Mello, CNTP, MNT and Dr. Miles Nichols, DAOM, MS, LAc

In a recent post we wrote about pyroluria, a genetic condition that is highly implicated in many mental health disorders including depression, anxiety and schizophrenia, as well as addiction and alcoholism. Pyroluria is best known for its tendency to deplete zinc and vitamin B6, which can lead to mood disturbances and inner tension. Although not as widely known, pyroluria also depletes other nutrients.

In this post we will continue the discussion by focusing on the role of omega-3 and omega-6 fatty acids in pyroluria. The omega-3 fatty acids EPA and DHA, mostly commonly found in cold-water fatty fish like salmon, sardines and anchovies are highly touted for their ability to reduce inflammation and positively impact mental health conditions. Omega-3s are now well supported in the research for the treatment of depression and anxiety (1) (2).

But as always, it’s critical to understand the mechanism behind each individual’s symptoms. Many different biochemical causes can lead to symptoms of depression and anxiety, and it’s important to view patients on a case-by-case basis. Pyroluria is a great example of this, because although many depressed and anxious people stand to benefit from increasing their omega-3 consumption if it’s deficient, doing so can actually make some people with pyroluria worse.

Terminology: mauve factor / HPL

As discussed in our previous pyroluria post, the term pyrrole refers to a whole family of chemical compounds. The specific pyrrole implicated in pyroluria is hydroxyhemopyrrolin-2-one (HPL), and researchers are now suggesting that pyroluria be renamed to “mauve factor” or HPL, which is the terminology we’ll use in this post.

Omega-3 and omega-6 balance

Omega-3 and omega-6 fats are both polyunsaturated fatty acids that must remain in balance with each other. It is now well known that the Standard American Diet is often too high in omega-6 fats, which in general tend to be pro-inflammatory, and too low in the anti-inflammatory omega-3 fats EPA and DHA. Mauve factor (pyroluria) adds an extra layer to the story, however, as it can interfere with the synthesis of omega-6 fats.

Without understanding this important caveat, many people who suffer from depression or anxiety supplement with omega-3 fish oil. In some cases, doing so may be counterproductive for people with high mauve / pyroluria. If high mauve is an individual’s underlying root cause, they may unwittingly push the omega-3 and omega-6 ratio too far in favor of omega-3 with high dose supplementation. We’ll see why this is a problem in the next section.

Omega-3s can worsen anxiety

There are reports of omega-3 fish oil actually contributing to symptoms of anxiety in some people. One interesting case study from 2015 relates an instance of a 55-year old man who reports mild panic attacks, general anxiety, shortness of breath and insomnia that result from taking fish oil.

He reports experiencing anxiety and insomnia for several months while taking fish oil supplements, symptoms which he says “largely disappeared” after stopping the fish oil. Several weeks later, he resumed fish oil again and experienced a recurrence of symptoms. After two days, he stopped the fish oil once again and saw his symptoms nearly vanish again. The case study report does not mention mauve factor or pyroluria, so we don’t know whether he was tested or not (3).

This is an area that needs further study. Sadly, there is not a lot of research on high mauve in general, probably because there is no pharmaceutical treatment for the condition. In addition to the case study above, several health websites and online forums report anecdotal cases of fish oil supplements worsening anxiety, such as a comment on this pyroluria blog post by Trudy Scott (4). Of course, these type of anecdotal reports must be taken with a grain of salt if not disregarded entirely, but in the absence of better quality research they are worth mentioning.

To understand why HPL / high mauve can cause low omega-6 fats, let’s look next at the biochemistry of the omega-6 pathway in the body.

Omega-6 fat synthesis

Low levels of omega-6 fats with pyroluria appear to result from a problem with the production of arachidonic acid (AA). This is different from the mechanism behind low vitamin B6 and zinc in high mauve. HPL depletes zinc and B6 by binding to these nutrients, which causes them to be excreted in urine. So it’s not that the omega-6 arachidonic acid is depleted in pyroluria, it’s that its synthesis is inhibited.

This block in AA synthesis appears to result from a problem with delta-6-desaturase, the enzyme which converts the omega-6 precursor linoleic acid into gamma-linoleic acid (GLA), which is then converted into AA. This same enzyme is also required for the synthesis of omega-3 fatty acids, so both omega-3 and -6 PUFA synthesis may be inhibited, but it appears that with high mauve, it’s more common for just the omega-6 eicosanoids to be affected. You can see where the delta-6-desaturase enzyme factors into PUFA synthesis here:

PUFA synthesis pathways

Delta-6 desaturase is required for the synthesis of omega-3 and omega-6 fatty acids

One study from 1986 on schizophrenia proposes a subtype of schizophrenia that is characterized by high linoleic acid, high fasting insulin and elevated urinary pyrroles / HPL. The authors explain this subtype as resulting from blocked delta-6-desaturase, which would yield elevated linoleic acid that is unable to be converted into GLA (5). To understand why the delta-6-desaturase enzyme underperforms, we need to look back at the two nutrients most associated with HPL – zinc and vitamin B6.

Zinc and Vitamin B6

As mentioned previously, zinc and vitamin B6 are the primary nutrients depleted in HPL. The depletion of these nutrients may explain the reduced activity of delta-6-desaturase and resulting deficiency of GLA, arachidonic acid and other downstream omega-6 fatty acids. Both zinc and B6 are cofactors required for the proper function of delta-6-desaturase (6) (7). Reduced omega-6 fatty acid levels may therefore be a secondary deficiency resulting from low zinc and B6.

EPA inhibits omega-6 eicosanoids

It’s interesting to note that EPA itself, a primary constituent of fish oil, inhibits the conversion of arachidonic acid into later stage omega-6 eicosanoids. In addition to zinc and B6 and the role these nutrients play in delta-6-desaturase, EPA itself may be implicated (8). This issue may present different sequelae than issues with D6D, as it comes into play in series 2 prostaglandins, which are synthesized from AA later in the omega-6 pathway than the previous issues. Many of the problems hypothesized to account for schizophrenia related to the omega-6 pathway have to do with prostaglandin E1 (PGE1), a series 1 prostaglandin.

As you can see from the flow chart above, PGE1 is synthesized from DGLA earlier in the pathway from DGLA before the synthesis of arachidonic acid, whereas several other prostaglandins and leukotrienes are synthesized from AA itself. It’s possible that by inhibiting conversion of AA into later stage eicosanoids, EPA may increase levels of other prostaglandins and leukotrienes by increasing levels of AA.

Other omega-6 pathway inhibitors

Alcohol is well known to exacerbate mood issues. Drinking alcohol has also been shown to inhibit both delta-6-desaturase as well as delta-5-desaturase, which catalyzes the conversion of DGLA into AA (9). Consequently, individuals with high mauve and low omega-6 levels would be advised to minimize consumption.

Trans fatty acids inhibit liver D6D activity in animal models and leads to decreased GLA and prostaglandin levels (10).

Fructose has also been shown to depress D6D gene expression in spontaneously hypertensive rats. The rats also had decreased levels ofomega-6 linoleic acid as well as its derivatives. Interestingly, D6D omega-3 gene expression decreased, yet activity of omega-3 D6D increased (11). By decreasing omega-6 D6D activity while increasing omega-3 D6D would lead to omega-3 dominance.

Chronic viral infections may also decrease D6D activity in both the omega-3 and omega-6 pathways. AA and EPA both have antiviral activity, even at low concentrations (12).

Diabetes also inhibits D6D and D5D activity, which is reversed by insulin in rat models (13).

Magnesium deficient rats exhibit decreased D6D activity and a slower conversion of linoleic acid to AA (14).

Now that we know some of the issues that can inhibit the omega-6 pathway and its prostaglandins, let’s move on to more detail about the prostaglandins themselves. Many of the effects of low omega-6 levels are manifested though low levels of its prostaglandins. As mentioned earlier, PGE1 in particular is implicated in schizophrenia.

Prostaglandins and pyroluria

Prostaglandins are classified as eicosanoid hormones and are found in virtually all cells in the body except erythrocytes (red blood cells). They are also involved in platelet activation, vasodilation and constriction and respiration. Other roles include altering glandular secretions, reproductive processes, platelet function and immune response. They also mediate inflammation, fever and pain. NSAIDs work by inhibiting cyclooxygenase (COX), a key enzyme in prostaglandin synthesis (15).

As mentioned earlier, Prostaglandin E1 plays a central role in schizophrenia. It is also relevant to mood disorders and is elevated in mania, the “high” side of bipolar disorder, and low in the depressive state. Another effect of alcohol, which we discussed in the last section, is that consumption stimulates PGE1 while drinking but leads to depressed levels afterwards, contributing to depression (16).

PGE1 also factors into gut health and has been shown to improve intestinal permeability (17). The gut-brain connection and role of intestinal permeability in mood disorders are well established at this point. Because high mauve can interfere with the synthesis of DGLA, which in turn can decrease PGE1, it may contribute to intestinal permeability and secondary symptoms of depression and anxiety.

The many effects of high mauve

As we’ve seen in this post, pyroluria or high mauve is not as simple as a zinc and Vitamin B6 deficiency. There are many other potential sequelae, including inhibited production of omega-6 fatty acids. As a result, PGE1 may be low as well, which has its own consequences for mood. Patients who know about the benefits of omega-3s for depression and anxiety may be supplementing high dose fish oil in an attempt to improve their symptoms. If they have high mauve and don’t know it, they may be unwittingly contributing to their symptoms.

Now that we know how high mauve can affect omega fatty acid balance and some effects of that imbalance, let’s move on to treatment recommendations, supplement recommendations and lab testing.

Treatment recommendations

It’s important to question patients thoroughly about their omega-3 intake from fish oil and cod liver oil as well as food sources like cold-water fish, grass-fed beef, flax seed and walnuts. Weighing benefits against potential issues is key. It can also be useful to question them about when symptoms of anxiety in particular started, how long they’ve been taking fish oil, and whether there is any correlation between the two. Patients may be unaware of the connection.

Supplement recommendations

In addition to the supplement recommendations in our last post, which focus primarily on B6 and zinc, it can be useful to supplement GLA in the form of evening primrose oil (EPO) or borage oil. Another option is to swap out their omega-3 fish oil for a combination product that includes GLA fatty acids as well. If a patient is not already taking adequate zinc and B6 that is the most important area to begin, and getting those levels up may help omega-6 eicosanoids as well because both B6 and zinc are required for proper D6D activity.

Testing options

The most important test when pyroluria, or high mauve is suspected is the urinary pyrrole test which evaluates the presence of HPL in the urine. This is the only way to conclusively diagnose high mauve. This urine test is the best starting point. We like the one from Health Diagnostics Research Institute. A questionnaire like this one by Trudy Scott can also be helpful if you are unsure whether testing is warranted. The questionnaire can also help with buy-in from the patient, as they can see how high their score is.

Another test that’s worth considering is an essential fatty acid test like the Essential & Metabolic Fatty Acid Analysis by Genova. This test reveals levels of omega-3 and omega-6 fatty acids in the blood and can help to identify whether they are out of balance. Another good option is a micronutrient test that looks at levels of zinc and B6 like the Vibrant Wellness Micronutrient Test. It’s also wise to compare zinc and copper levels as the two need to remain in a certain ratio with each other.

In summary

In this post we’ve explored how pyroluria, or high mauve can affect fatty acid balance and potentially lead to low levels of omega-6 fats. We also examined how low levels of these eicosanoids can also affect prostaglandins like PGE1, and how that may contribute to symptoms of depression, anxiety and even schizophrenia. If you have patients with pyroluria who have made incomplete recovery even after supplementing with zinc and B6, it may be worthwhile to look at omega-6 eicosanoids and PGE1. That may be the missing piece!

Ideas for those who have tested for or strongly suspect high mauve / HPL:

  • Cover the bases with zinc and vitamin B6 (see previous post for more details)
  • Limit supplementation with fish oil and moderate cold-water fatty fish intake*
  • Add GLA from evening primrose oil
  • Limit or eliminate alcohol intake
  • Add magnesium glycinate, taurate, and/or l-threonate (total of 400-1000mg daily)
  • Limit fructose consumption (aside from a moderate amount of whole phytonutrient-rich fruits)
  • Test for chronic viral infections and work with a functional medicine practitioner to resolve them

*Fish oil must be weighed with an understanding of benefits and possible issues. There was great cardiovascular promise from early short-term fish oil studies. Later long-term studies did not show significant benefit. There is some concern with high dose fish oil for long-term use for anyone, not just those with high mauve / HPL. That being said, there is of course some anti-inflammatory benefit from a healthy omega 3 : 6 ratio. This must also be considered. In the case of high mauve / HPL, extra attention and care should be taken to observe if a level of omega 3 may be a cause of worsened anxiety and/or depression.


  1. Martins, Julian G. “EPA but Not DHA Appears To Be Responsible for the Efficacy of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation in Depression: Evidence from a Meta-Analysis of Randomized Controlled Trials.” Journal of the American College of Nutrition, vol. 28, no. 5, 2009, pp. 525–542., doi:10.1080/07315724.2009.10719785.
  2. Bozzatello P, Brignolo E, De Grandi E, Bellino S. Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data. Brown L, Rauch B, Poudyal H, eds. Journal of Clinical Medicine. 2016;5(8):67. doi:10.3390/jcm5080067.
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  4. Scott, Trudy. “The Anxiety Summit: How Zinc and Vitamin B6 Prevent Pyroluria and Social Anxiety.” everywomanover29, Trudy Scott, 31 May 2016,
  5. Heleniak, E.p., and S.w. Lamola. “A New Prostaglandin Disturbance Syndrome in Schizophrenia: Delta-6-Pyroluria.” Medical Hypotheses, vol. 19, no. 4, 1986, pp. 333–338., doi:10.1016/0306-9877(86)90106-4.
  6. Yary, T., et al. “Omega-6 Polyunsaturated Fatty Acids, Serum Zinc, Delta-5- and Delta-6-Desaturase Activities and Incident Metabolic Syndrome.” Journal of Human Nutrition and Dietetics, vol. 30, no. 4, July 2016, pp. 506–514., doi:10.1111/jhn.12437.
  7. Bordoni, A, et al. “Dual Influence of Aging and Vitamin B6 Deficiency on Delta-6-Desaturation of Essential Fatty Acids in Rat Liver Microsomes.” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 58, no. 6, 1998, pp. 417–420., doi:10.1016/s0952-3278(98)90163-6.
  8. Culp, Brenda R., et al. “Inhibition of Prostaglandin Biosynthesis by Eicosapentaenoic Acid.”Prostaglandins and Medicine, vol. 3, no. 5, 1979, pp. 269–278., doi:10.1016/0161-4630(79)90068-5.
  9. Nervi, Anibal Mario, et al. “Effect of Ethanol Administration on Fatty Acid Desaturation.” Lipids, vol. 15, no. 4, 1980, pp. 263–268., doi:10.1007/bf02535837.
  10. Kinsella, J E, et al. “Metabolism of Trans Fatty Acids with Emphasis on the Effects of Trans, Trans-Octadecadienoate on Lipid Composition, Essential Fatty Acid, and Prostaglandins: an Overview.” American Journal of Clinical Nutrition, vol. 34, ser. 10, 1981, pp. 2307–18.10.
  11. Comte, C., et al. “Effects of Streptozotocin and Dietary Fructose on Delta-6 Desaturation in Spontaneously Hypertensive Rat Liver.” Biochimie, vol. 86, no. 11, 2004, pp. 799–806., doi:10.1016/j.biochi.2004.10.002.
  12. Puri, B K. “Long-Chain Polyunsaturated Fatty Acids and the Pathophysiology of Myalgic Encephalomyelitis (Chronic Fatigue Syndrome).” Journal of Clinical Pathology, vol. 60, no. 2, Feb. 2006, pp. 122–124., doi:10.1136/jcp.2006.042424.
  13. Rimoldi, Omar J., et al. “Effects of Diabetes and Insulin on Hepatic Δ6 Desaturase Gene Expression.” Biochemical and Biophysical Research Communications, vol. 283, no. 2, 2001, pp. 323–326., doi:10.1006/bbrc.2001.4785.
  14. Mahfouz, M. M., and F. A. Kummerow. “Effect of Magnesium Deficiency on Δ6 Desaturase Activity and Fatty Acid Composition of Rat Liver Microsomes.” Lipids, vol. 24, no. 8, 1989, pp. 727–732., doi:10.1007/bf02535212.
  15. Tortora, Gerard J., and Bryan Derrickson. Principles of Anatomy & Physiology. John Wiley & Sons, 2012.
  16. Horrobin DF, Manku MS. Possible role of prostaglandin E1 in the affective disorders and in alcoholism. British Medical Journal. 1980;280(6228):1363-1366.
  17. Empey, L.r., and R.n. Fedorak. “Effect of Misoprostol in Preventing Stress-Induced Intestinal Fluid Secretion in Rats.” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 38, no. 1, 1989, pp. 43–48., doi:10.1016/0952-3278(89)90146-4.
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