This is an issue, I believe, we really do look at backwards. I suppose it is easier to blame to person when as clinicians we are lost in the forest. In so many areas we do this, but there just isn't sufficient evidence to support the long held belief that individuals with #anorexia are intentionally starving themselves in an attempt to gain control over some area in their lives or even that their parents are somehow to blame. We know better now. We need to do better.
Previously I wrote about anorexia and the underlying #malnourishment that can lead to this disorder. Nutritional supplements are exceedingly important; it is no understatement to say, in fact, that they are critical. Zinc deficiency is a significant concern with anorexia, so much so that one should assume those with weight concerns, whether obese or severely underweight, are likely to have a zinc deficiency. Niacin and the various B vitamins have also been identified as a contributor to anorexia and were discussed in a previous post.
My recommendation to most clients, well or dis-eased, is to evaluate their genetic profile so we can work with any known SNPs, including #MTHFR. This particular mutation, if you will, is quite common in our country and involves methylation which utilizes #folate, or vitamin B9. Folate is the term which refers to vitamin B9 found in our foods naturally, but many are more familiar with the synthetic form, folic acid, which is found in our fortified foods and supplements. L-methylfolate is the natural, active form of folate used at the cellular level and the only form which can cross the blood-brain barrier to be utilized by the brain. This is a significant issue with those suffering with anorexia, particularly those with #depression who are not responding to treatment.
Folate is important for so many neurological functions. It is critical for the biosynthesis of #neurotransmitters, myelination of neurons, regulation of gene expressions, amino acid metabolism, cell division, and I think most people, at least all people who have been pregnant are familiar with the importance of folate (folic acid) in prevention of neural tube defects. It can also reduce homocysteine and is necessary for DNA replication. It may be most important in the role of DNA repair, for the prevention of cancer.
Interestingly, many drugs that we use in clinical practice deplete our bodies of folate and that's for everyone, but those with an MTHFR mutation to any degree are going to really struggle with obtaining the necessary folate to meet their physiologic needs. Anticonvulsant drugs, oral contraceptives, niacin, and some blood thinners can deplete folate, as well as a number of anti-depressants. Diabetes, gastritis, Crohn's, colitis, #hypothyroidism, and gastric bypass are diseases which contribute to insufficient folate, while excessive #alcohol, smoking and poor nutrition, even obesity can also deplete folate levels in the body. Low folate increases the incidence of depression and these people have poorer responses to antidepressants and higher rates of relapse.
Genetic Polymorphisms: MTHFR
There are three variations of MTHFR, with one SNP decreasing #methylation by 45 percent. Even some inability to convert folic acid to folate or methylfolate will impact the body's ability to convert L-tryptophan to 5-HTP to serotonin and ultimately, melatonin so to my amazement, this isn't even evaluated when treating clients with depression. Vitamin B6 and zinc are important in these processes as well.
When MTHFR is identified in genetic testing, L-methylfolate is recommended anywhere from 1mg to 25mg daily, with 7mg to 15mg more common. There are prescription brands, although these can have lots of dyes. Enlyte has several forms of folate in its supplement, and then your functional or integrative provider can recommend a number of nutriceuticals with 1mg to 5mg supplements. When treating a patient with anorexia, we try to give them a supplement with the gamut B vitamins. Be aggressive with anorexic clients who have MTHFR as this may be the underlying issue for those refractory cases, particularly the T/T variant. Blood levels aren't always helpful as they are also measuring the synthetic version, which isn't utilized in some.
Thiamine (Vitamin B1)
We forget about the consequences of these vitamin deficiencies because we believe them to be cured. Thiamine deficiency or the result of such is called beriberi. It is a water-soluble vitamin and plays a critical role in energy metabolism and cell development and function. We find it in unrefined whole grains, yeast, legumes, beef, pork, fish, and milk. When thiamine is low, the mitochondria in our cells, the powerhouse, just stops. We see this bariatric surgery, congestive heart failure, eating disorders, alcoholism, hyperemesis gravidarium, and of course, malnutrition.
When deficiency is severe we see heart failure, ataxia, neuropathy, delirium, and confusion, but more marginal symptoms are mental fatigue, emotional lability, paresthesia, chest pain, tachycardia, weakness, myalgias, back pain, nausea and vomiting. Dysautonomia or the malfunction of the autonomic nervous system is the malfunction of great importance with thiamine deficiency. This causes inappropriate sinus tachycardia, neurally-mediated hypotension, pure autonomic failure, vasovagal syndrome, mitral valve prolapse dysautonomia, cerebral salt-wasting syndrome, neurocardiogeneic syncope, autonomic instability, and the more common, postural orthostatic tachycardia syndrome (POTS).
The latter, POTS, is so common now, that Boston has created POTS clinics to address those suffering this disorder. Common to anorexia, those with POTS will suffer orthostatic intolerance or low blood pressure after standing up, causing lightheadedness or fainting. They may also notice an increase in their heartbeat by up to 30 beats per minute or a heart rate of more than 120bpm within ten minutes of rising. Other symptoms include weakness, dizziness, sleep disturbances, and fatigue.
POTS affects an estimated 1,000,000 to 3,000,000 Americans, primarily women. One in one-hundred teenagers have POTS. Keep in mind, this isn't just a risk for those with anorexia or even alcoholics, but also those who are obese and may have high calories, but low nutritional opportunity. Consider that thiamine modulates acetylcholine release and thus affects synaptic transmission. Deficiency can affect neuron transmission at the peripheral ganglia and reduce nitric oxide production leading to vascular dysfunction.
Clinically a thiamine level should be evaluated, but also a transketolase test to identify severely low thiamine. Supplementation would then begin with vitamin B1 cream, 40mg/day. In one study of POTS patients, when offered thiamine hydrochloride 100mg daily for four weeks, all were restored to normal. Genetic abnormalities may be affecting metabolism. Several case studies exist regarding thiamine deficiency. One in which a client only ate a bowl of grapes daily, losing 135 pounds in five months, and was diagnosed with AN and Wernicke encephalopathy. She received IV.thiamine and multivitamins after presenting with paresthesia, weakness, vertigo, inattention, ataxia, and double vision.
Significant improvement is seen for those with B1 deficiency through supplementation, as much as 100mg twice daily. Consider this when working with alcoholics, which can be difficult to identify, and especially those with anorexia, even obesity.
Inositol: Vitamin B8
Simple. Safe. No side effects to supplementation. Inositol is a sort of second messenger in that it tells serotonin what to do. Inositol may have therapeutic effects in the spectrum of psychiatric illnesses responsive to SSRIs, including depression, bulimia, panic disorder, and OCD. Autism may even be effectively treated with vitamin B8. There are double-blind, placebo-controlled trials so we can no longer say this isn't supported by literature. Most human studies have offered 10-18 grams of inositol, some though have found positive results with only 2grams or less per day but gastrointestinal discomfort can result so start low.
Obsessive thinking can be reduced, enabling patients to more easily "turn off" the thoughts that interfere with sleep. This one is one of the more simple approaches to intrusive thoughts that sometimes even cause people to drink to sleep. OCD is quite common in those with eating disorders so again, an easy treatment. Inositol can be supplemented alongside an SSRI, starting at 1/4 tsp powder BID for children and 1/2 tsp powder BID for adults, increasing every five days with the average dose at about 1 tsp, three times daily or about 8.4 grams. Certainly consider this for insomnia, OCD, depression, #panic disorder, bulimia nervosa, binge eating disorder, and antidepressant withdrawal.
Vitamin D
Critical for calcium homeostasis, growth and regulation of all body tissues, regulation of #iron, #zinc, and manganese metabolism, vitamin D is paramount for optimal health, yet about half of all people in the United States are deficient. My own clinical experience has demonstrated deficiency much higher than this, with nearly all clients needing supplementation. While the vitamin D level can speak volumes to lifestyle choices, it can also be attributed to genetic factors. Sun is critical, but there are #polymorphisms which can contribute to deficiency so consider this when supplementation seems to fall short. (Also evaluate magnesium levels.)
Vitamin D does impact neurological function as well as bone health. Bone density may be an important evaluation in clients with anorexia. The prefrontal cortex, hippocampus, cingulate gyrus, thalamus, hypothalamus, and substantia nigra are all dependent on vitamin D for optimal function.
The other important part for why we are interested in vitamin D though, for clients who are anorexic, is because of its relationship to #tryptophan and #serotonin synthesis. There is an enzyme called TPH2 which converts tryptophan to serotonin, critical for anorexic clients, but dependent completely on vitamin D status. The TPH2 is responsible for producing all of the brain's serotonin, which goes on to make melatonin. Anorexia clients are known for having chronic sleep disturbances so this should not be ignored. The literature here is embarrassingly strong so there just is no excuse for neglecting this underlying issue in clients.
Depressed individuals have a 65 percent greater likelihood of having lower vitamin D concentrations, and 58 percent of those who attempt #suicide are vitamin D deficient. This correlation may be somewhat related to higher levels of pro-inflammatory cytokines IL-6 and IL1B in those with lower vitamin D. This is fairly dramatic, but also fairly simple. Inflammation is the cornerstone of dis-ease.
Optimal levels or the exact target for vitamin D is a bit more controversial. I talk about this a bit more in another post, but clearly below 20 is deficient, and ultimately the CDC recognizes this level as sufficient enough to create dis-ease states. Levels 20-39 are generally considered inadequate (bone loss occurs below 30), with 40-50 fairly acceptable by most all clinicians. There are many integrative and functional providers though who propose a more optimal level closer to 60, some even aiming between 60 and 80. Certainly levels above 200 are potentially toxic. Consider testing twice each year. Don't supplement blindly. Understand your baseline.
Dysbiosis, Probiotics & the Gut Fascination
Certainly no functional medicine provider can talk about any dis-ease process and not also discuss gut health, so let me define a few terms and remind you of the important role our gut #microbiota plans in our overall health. Consider that that gut has more than 1kg of bacteria or 2.2 pounds, anywhere from 300 to 3,000-plus species of bacteria, and more than 5 million different #genes. Even more impressive, the gut has ten times the number of cells than you have human cells in your entire body and 200 hundred times the number of genes than your own human genes, so you are more bacteria than you are actually human! No question the gut microbiome plays an important role.
You've heard the #gut be referred to as the second brain, and this is no exaggeration. The brain has 85 billion neurons while the gut has 500 million. The brain has at least 100 neurotransmitters, and 40 of these have also been identified in the gut. Half of our #dopamine production occurs in the brain, while the other half is produced in our gut. Ninety-five percent of #serotonin is produced in the gut, and only 5 percent in our brain. The gut-brain axis or superhighway is incredibly significant. Tons of research here and growing all the time - much more will come into the near future I anticipate, so again, clinicians really need to get on this train.
The #microbiota is the entire population of microorganisms that colonizes a specific region or location, whereas the #microbiome is the totality of genetic material or the entire collection of genes contained within any given microbiota. Probiotics are the live microorganisms that benefit the health of the host when administered in adequate amounts. Psychobiotics is a newer term and refers to the live microorganisms capable of influencing host cognition and/or behavior via the GBA.
We now understand that the microbiome influences our #neurotransmitters, affects appetite and weight, harvests calories and vitamins, and supports hunger, cravings, and satiety. Probiotics increase plasma tryptophan levels, decreases serotonin metabolite concentrations in the frontal cortex, increases dopamine metabolite concentrations in the amygdaloid cortex, increases acetylcholine levels, and increases GABA levels.
The synergistic relationship between the mind and the gut is only in its infancy, I have no doubt. What we do know is that this balance is that it is a bit delicate. Antibiotics, stress, infections, laxatives, radiation, steroids, diet high in sugars, birth control pills, alcohol, and deficiencies in zinc, B vitamins, and essential fatty acids can decrease good bacteria. Diet though is the single most influential factor affecting the microbiota, particularly for those with anorexia.
Diversity is also critical. In my own clinical experience, clients may present as if they have dysbiosis in spite of taking probiotics, and when evaluated via stool tests, we discover very little diversity. For this reason, I have been recommending clients rotate through the better brands as opposed to sticking to any particular one, even if opting for a high quality brand or blend. It's the behavior among these bacteria that are important, as well as the total load. Again though, any intervention is helpful. We even have evidence that choosing yogurt over milk is helpful in improving mental/emotional health.
One study found those with anorexia have specific stool bacterias that have not been found any healthy individuals. They have even been named for their hosts: clostridium anorexica massiliense and clostridium anorexicus. Obese clients also suffer with altered bacteria in their gut, but an interesting study on 20 obese subjects and 9 with anorexia compared to 20 healthy controls found that anorexic patients had reduced levels of Lactobacillus and increased levels of M. smithii compared with obese and healthy individuals. Perhaps there is some sort of adaptive use with nutrients. This study has been repeated with very similar results. The gut in those with anorexia is essentially the opposite as those with obesity.
Aim for 20 and 100 billion CFUs. Change the strain or brand or blend with every bottle purchase. Omega-3 deficiency induces dysbiosis, so evaluate here and supplement as necessary. These are all simple concepts. These aren't difficult interventions to implement, but they are profound in their impact on very complex issues. We can change our gut biome within days. There is a great deal of hope here.
Anorexia & Co-Morbidities
These clients often have trauma which is really the more difficult aspect to treat. Anorexia is incredibly complex, as are most all conditions of chronic health. Those with anorexia rarely seek help, which is complicated by their lack of trust in healthcare professions, which is certainly earned. However, these clients do have a higher tendency for paranoia and OCD. There are few consistent treatment models, if any, with no real understanding of the underlying etiology and no pharmacologic treatment protocols. Research dollars in this area are nil. There just isn't a lot of interest here for whatever reason. We treat these individuals similar to those with obesity in that we want to tell those who are quite thin to just eat and those who are quite obese to exercise and eat smarter. The functional investment has been neglected, particularly the mind/bony connection. Eating disorders should be seen as reflections of multiple areas of physiology. Treat the malnutrition and these clients can have a much better chance of recovery.
I came across your blog post while I was researching vitamin/mineral difficiencies for people with EDs. I've had an ED for 30 years and also have MTHFR. I found this post to be very interesting. I've never had an issue with my folate, although I was taking folic acid up until 2 years ago. I'm having my labs done tomorrow, so I'll be interested to see what my numbers are. I think everything will check out okay, but I'm losing a ton of hair, so my doctor ordered the vitamin/mineral labs. I also have UC, so we shall see. I look forward to reading more of your posts.