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clear search termsDis-ease Begins in the Gut! Or Does it? Another case of Interconnectedness
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A question from a Practitioner:
I have a 54 year old perimenopausal patient with erratic cycles who seems to have a lot going on: IBS (though notably much better since starting DGL, Mg, HCL, and digestive enzymes), joint pain (esp. knees and definitely curtailing her activity), frequently feels cold, low mood, low energy, low libido, ridged nails, coarse hair, dry skin, wrinkled skin, extra weight in thighs, hips, and butt, difficulty building muscle, weight gain (10 lbs over 2 years), has had fibroids in the past, fibrocystic breasts. She occasionally gets rashes……usually in winter. She already has a very clean diet, eats all organic, grass fed meats, gluten & dairy free, and mostly sugar and flour free. Caffeine free. Alcohol free except for maybe 1 drink/month; she says the alcohol makes her feel more depressed. Overall, I think thyroid is at play here, but it might be more complex than that. She is definitely interested in doing more functional testing to know for sure what is at play. Please see the details below; what do you think?
Supplements: She takes D3, fish oil, krill oil (her PCP wants her to take both), K2, C, Meriva, hyaluronic acid, zinc, iron, Mg, DGL, HCL, digestive enzymes, iodine drops and methylated B-complex (she has MTHFR SNPs).
Labwork. She has been on the above supplements for at least 3 months, yet recent labs show her ferritin is at 19 (RR 13-150). Her alkaline phosphatase (U/L) is 41 (RR35-105) which I believe that is perhaps indicative of zinc deficiency? Albumin is 4.6 (RR is 3.5-5.6), and Total protein (g/dL) is 6.5 (RR 6.6-8.7) I believe this is insufficient, though she eats a healthy diet with lots of protein and takes HCL with every meal. Here’s other labwork:
- Blood sugar looks fine (fasting glucose is 86, HbA1c is 4.8, fasting Insulin is 6.1).
- WBC 4.57 (RR 3.98-10.04). Maybe toxicity? She has 9 silver fillings. Possibly some immunodeficiency? Chronic viral activation?
- MCV 97 (RR 79.4-94.8). Last year it was 93. She’s already taking a methylated B-complex though, so you would think this would have gotten better. So probably there is some deeper absorption issues going on? Or perhaps just not enough?
She’s done an adrenal panel and is waiting for results. I suspect the adrenals are at play here too.
Sex Hormonal bloodwork panel came back as follows but this is just from blood, so I know it’s not thorough (taken on Day 21 of her cycle):
- DHEA-Sulfate 27.1 (RR 35.4-256.0 ug/dL) low!
- Testosterone <2.5 (RR 2.9-40.8 ng/dL) low!
- Free testosterone <0.1 (RR 0-4) low!
- Sex Hormone (SHBG) 177.2 (RR 17.3-125.O nmol/L) high!
- Estradiol 27.0 (menopausal <31)
- Progesterone 0.3 (no RR but marked as at target)
I just wanted to add that we did a food sensitivity test which came up basically negative for everything. The three things that were listed as avoid were things she doesn’t eat.
ferritin 19 RR 13-150 ng/mL
iron 56 RR 37-145
Normal kidney tests. All liver enzymes are in moderate lower half of reference range. Lipid panel all looks optimal.
Her PCP did a thyroid panel:
- Free T3 (pg/mL) 2.7 (RR 2.0-4.4)
- Free T4 (ng/dL) 1.1 (0.9-1.7)
- TSH (IU/mL) 2.410 (0.111-4.910)
- Reverse T3 (ng/dL) 26.9 (11.6-29.7)
- No TPO or Tg antibody elevation
Her PCP put her on levothyroxine 13mcg. After 3 weeks, if she is not feeling any better, the PCP intends to increase to 25 mcg at 1 month but has not offered T3. I want to educate her on the value (and perhaps critical importance?) of supporting with T3 as well, so she can advocate for herself.
So I am looking at sex hormone support as well as thyroid support: Is it best to treat one first and then the other? But shouldn’t the gut come first? She is clearly not well absorbing enough nutrition from her food or from her supplements. Where to start?
SAFM Answer from Tracy:
Indeed, this is perhaps the question that can befuddle FM practitioners the most: where to begin?! As the proverbial riddle says, “Which came first: the chicken or the egg?” And the answer, of course, is “Both!” Your patient is an ideal example of the interconnectedness across systems in the body and how progressive imbalance or dysfunction in multiple systems can synergistically create a downward spiral for all of them. It’s also a good example of why our support for complex patients requires layers of progressive support in a logical order vs. trying to address too much at once and too quickly. The body needs time to heal!
Many practitioners would dive right into addressing the gut and what dysbiosis (SIBO?) might lie there. We often want to do something aggressive right from the beginning! But I don’t agree in this case. Inadequate thyroid function is going to continue to impair the immune system and nutrient absorption/digestion. Even beyond that, a potent stress response is hampering thyroid function, the immune system, sex hormone balance, and digestion. We could address a dysbiosis only to acquire another one a few months later. However, the gut is key here as poor digestion/absorption is making the thyroid ineffective and impairing immune function. See the interconnectedness?! There are many possible, logical approaches in this case, and I am happy to share what I recommend in light of what you’ve shared. But you should, of course, see if it resonates with your patient and with your intuition as her personal provider. As is often the case, I believe a focus *first* on fundamentals is likely going to help this patient the most. I would prioritize (1) stress relief and calming of stress hormones, (2) increased digestive support, and (3) improving thyroid function. This will set the stage for the body, downstream from these, to optimize sex hormones and immune function sustainably on its own. Let’s delve into the details…
First of all, let me say that your read of the available labwork is quite good. Insufficient zinc (ALP), insufficient iron (ferritin), insufficient B12 and/or folate (MCV), etc..
Let’s talk about dis-ease beginning in the gut. I believe she definitely has hypochlorhydria and that the HCl support she is using presently is simply insufficient. It is important to ensure that each patient like this complete an HCl Challenge Test (this is covered in details in the Disease Begins in the Gut 101 Deep Dive Clinical Course) in order to identify the level of HCl support they need for their unique body (at this unique time). Some find they only need 1 cap per meal (650mg HCl), while others need 6-7 per meal. Low thyroid function and high stress hormone levels (sympathetic dominance) directly impair digestive secretions. I would also spend time educating her about the power of relaxed, mindful eating hygiene and how powerful this simple habit can be in improving digestion and absorption.
I also think we need to heal and nourish the intestinal lining in order to ensure optimal nutrient absorption. She is lacking sufficient iron and zinc (and likely selenium) in order to optimally convert T4 to T3 thyroid hormone, and these markers (e.g. ALP, ferritin) remain low despite three months of supplementation. Given this data, it’s also likely that DGL on its own – even with the zinc – is not enough support. I recommend she begin using something comprehensive like Designs for Health’s “GI Revive” once daily at night before bed (for 4-6 weeks). If it resonates with her, bone broth can also be very effective and a calming, soothing snack once or twice a day.
But let’s get to the elephant in the room: STRESS. Mental-emotional stress and/or physiological stress (e.g. microbial imbalance, as we often see with chronic IBS, toxicity, food sensitivities) can also create HPATG imbalance (e.g. high stress hormones and low sex hormones) as the body prioritizes survival over thriving. High SHBG and high Reverse T3 are classic hormonal signs of strong stress as the body implements a purposeful skewing of active hormones (that is, those available for cellular effects). Even with low total hormone levels (which is all we can tell from the limited utility of blood data), the high SHBG is preventing them from having cellular effects. Reverse T3 competes for thyroid hormone receptors with Free T3, impairing cellular metabolism to conserve fuel as a survival mechanism. And her T4 to T3 conversion is already struggling. She may also have impaired methylation (given high MCV; you could further validate with homocysteine data) which is necessary to break down stress hormones once they are generated (and various SNPs can further impair this e.g. COMT). You could learn much more from comprehensive urinary hormone testing (e.g. DUTCH), but I would not pursue that for a while – perhaps after ~3 months of support with these fundamentals. We need to remember: the body is very wise, and we don’t often need to “force” hormone balance with interventions. When we remove and calm what the body perceives as threatening, the HPATG axis will naturally shift.
Insufficient stomach acid is causing maldigestion and thus low availability of amino acids and minerals, in particular. Her Total Protein is definitely suboptimal, and her Globulin at ~1.9 is clinically low. As such, an antibody-based food sensitivity test is highly likely to be inconclusive. However, you might revisit the data and see if even the low-grade “mild” reactions are to foods that she eats frequently. It may also simply be that her overall IgG is simply too low to render comparable data against the lab’s norm levels. We often find that persistent, low-grade inflammatory immune system reactions to foods or microbes is at play in chronic joint pain and can, over time, create HPATG imbalance via cortisol. Our students find that nightshade vegetables, dairy foods, and gluten-containing grains are common culprits in osteoarthritis.
Your patient has many symptoms of insufficient zinc, especially those related to the skin and hormones. As much as it would be helpful to have RBC zinc data in this case, given her symptoms and the low alkaline phosphatase, I would make sure she is using at least 40mg daily with food for ~6 weeks and also a bioavailable form, ideally picolinate but perhaps citrate. Beyond ~6 weeks, I would use a zinc: copper blend such as OptiZinc (in a ~15-20:1 ratio), but I would allow zinc to be boosted more aggressively, separately, first. And make sure she is not taking her zinc supplement with the same meal as her iron (which should be paired with her vitamin C to enhance absorption). Many minerals compete for absorption, and in this case, timing may be making a significant difference in what she can absorb. Brazil nuts are an excellent source of selenium (4-5/day), and this is key for T4 to T3 thyroid hormone conversion as well.
Her Vitamin D level is quite high which can suppress immune function directly – and also perhaps via depleting Vitamin A which is also critical for healthy skin and immune function. I would recommend she cut back on her Vitamin D3 supplement to get her Vitamin D to a more moderate zone of 40-60 ng/ml.
There is clear evidence of hypothyroid function here both in her data and in her persistent symptoms. Free T4 thyroid hormone level is suboptimal (perhaps indicating insufficient medication dosage), and as above, poor T4 to T3 conversion and stress is having an impact, diverting thyroid hormone into the inactive Reverse T3. It often takes a few trials to find optimal thyroid hormone dosing, so encourage her to be persistent with that process. She will need to see if she thrives on the T4-only medication; some people do, while many others do not and need a natural thyroid extract instead. As she boosts stomach acid, she will better absorb amino acids to help with making more thyroid hormone, but for the moment, her medication is likely fully suppressing her own endogenous production; hence the importance of having her prescription dose be sufficient to bring her up to optimal levels. I also recommend ~1/2 tsp daily of kelp granules in her food to boost iodine and many other trace minerals (instead of iodine drops). Indeed, her ferritin is very low, but we don’t know just how low it was beforehand! Iron is notoriously, poorly absorbed; check the form/type. I have had several clients have excellent results on Terry Naturally’s “Liver Fractions”, so given her results, it might make sense to make a change. We need good gut function to nourish the thyroid, and we need ample thyroid hormone to allow optimal gut function (in terms of both motility/digestive secretions and also immune function to maintain optimal microbial balance). Again: interconnectedness at play!
The increasing MCV indicates some macrocytic anemia which can definitely contribute to fatigue. Typically either insufficient Vitamin B12 and/or Folate are involved here, so to your point, the B-complex she is using is insufficient in one or both directions (or as above, is just being poorly absorbed). I would ideally seek homocysteine labwork, so you have additional insight into if/how her MTHFR SNPs are actively impairing folate in reality right now. Otherwise, I would probably boost HCl (per her experiment above), keep her methylated B-complex support as-is, and add in a separate adenosyl/hydroxy B12 (e.g. Pure Encapsulations) for a ~2 month trial and then check her MCV again as well as Homocysteine and serum B12 (to check absorption). Methylation is a key focus for her not only because of her known SNPs (and she may have others of course e.g. MTR/MTRR), but due to its critical roles in hormone and neurotransmitter metabolism as well as glutathione synthesis to counter oxidative stress.
I know you will work with her on mental/emotional stress sources and optimizing her self-care. This will directly affect the HPATG axis. She seems to put strong faith and preference into supplements; if so, to lower SHBG, you could recommend stinging nettle root (not leaf) ~150mg twice daily. This should help her overall with low mood, low libido, low energy. I also recommend maca root (1 tsp to 2 Tbsp) that she might add to a daily smoothie, for the same reasons as it can increase hormone action at the receptor level. Yes, all hormones affect each other, including thyroid and sex hormones, and cortisol acts as a master hormone. We need to remember – and educate our patients – that the body orchestrates a particular skew in our HPATG axis given the environment in which we are asking ourselves to try to thrive.
Support her with the fundamentals…self-care, relaxation, mindset shifts, deep sleep, consistent eating hygiene. There is much to work on here! But it can only be done one layer at a time. Patiently and logically. I hope this is helpful to get you started. You may indeed eventually want to do further testing about gut imbalance, but I have also seen many times how stress reduction and optimizing thyroid/adrenal function can help the body to remedy its own imbalance and return to greater vitality.
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Hi Tracy,
This post seemed to target what I am thinking in supporting a 60 year old women with Crohn’s disease, IBS-D, extreme weight loss, lack of energy, painful neuropathy and unable to eat most everything. I am working on supporting parasympathetic nervous system function and rest-and-digest and am having her add some bone broth; she feels she is not ready for GI Revive yet. I cannot get any supplements into her to help with digestion as she can not tolerate anything as of yet. I want to be able to supplement with magnesium. I know a stool test is key here, and i want to refer her to a functional medicine physician. I am thinking that relaxation and gut healing are key, however, and no one can do anything unless she is able to ingest and nourish herself. Thank you for your thoughts!
Your focus on stress relief and mindfulness is indeed key. I would add to this a focus on eating hygiene and also consuming entirely cooked foods for now. Broths and soups may indeed be particularly nourishing. I agree 100% that a referral to a FM physician is a wise step, and I would use the “find a practitioner” tool at http://www.functionalmedicine.org for that purpose. In terms of your support, I would remember foremost that Crohns disease is autoimmune; I believe that the most important intervention right away is eliminating all gluten, dairy, and grains from the diet. I would use Metagenics “UltraInflamx Plus 360” as a daily medical food as a first priority. And indeed, I would add in GI Revive as soon as possible to soothe and heal the gut lining (just start small with ~1/4 of typical dose and build up gradually to 2x/day). In my experience, this combination alone – especially while awaiting stool test results – can often provide some critical triage, especially in reducing number and urgency of bowel movements. A comprehensive stool test will indeed help to pinpoint specifically the level of inflammation, which digestive function needs support, and the particular dysbiosis at play… Read more »
Hi thank you so much for the reply. I had food sensitivity testing done two years ago and eliminated all of the offending foods for 8 months and then slowly reintroduced some of them. As for dairy I currently only take colostrum as well as I also use some Grass Fed Buffalo Kefir as buffalo dairy showed clear on my sensitivity test.
So what I did was stopped all my supplements and then went full in to six capsules per meal of HCL and my eczema lightly flaired up and began to clear. I am now at 16 days full six capsules per meal HCL and all is getting better every day. eczema is mostly all cleared up and I am feeling better every day.
I’ve thoroughly enjoyed the webinar today about the gut’ s interconnectedness. Definitely adding glucoronidation to my vocabulary list!
How I’d love to win a seat in the Disease Begins in the Gut course! The knowledge obtained will be shared far and wide to help raise awareness of this vital connection!
Thanks much!
Jane Phillips
I would like to better understand how an antibody-based food sensitivity test is highly likely to be inconclusive for folks with low stomach acid which renders less minerals and amino acids. Is it because those building blocks are needed to synthesize the antibodies which essentially are proteins? Also, if indeed, even the low-grade “mild” reactions are to foods that this client eats frequently, could this be indicative of leaky gut, despite the usual threshold of ~8 plus high grade sensitivities that we look for for intestinal permeability?
It’s not so much that hypochlorhydria will necessarily drive this dynamic; it’s the low globulin that is of note in this case. For example, a person might have hypochlorhydria and clinically low albumin (because of poor amino acid availability) but still have high globulin as an indication of an antibody-mediated inflammatory response. We need to keep in mind that food sensitivity testing is already vulnerable to false readings, so I personally would not recommend it when globulin is clinically low. I appreciate the thought process you offer on using the data anyway, but I think your assumption is a stretch. It’s quite normal for any healthy person to have low-grade mild reactions to a wide variety of foods, especially those consumed regularly, as the immune system assesses and promotes tolerance.
I am a Male 51 years young with A+ blood type, i have a deviated septum that causes acute post nasal drip and phlegm that all contribute to hypochlorhydria. I have eczema as well. I am a health coach and eat really clean, don’t take any medications, and am very fit. I was taking HCL, however, I was still experiencing symptoms of tiredness after eating so when I heard of the HCL challenge I immediately began to increase my does and got some great relief from the gas and tiredness only to have a huge eczema outbreak so bad that I had to stop. Any ideas how I can proceed?
I have a few thoughts which might be helpful. If you were well tolerating a lower dose, it seems unlikely that you have an allergy or sensitivity to the supplement ingredients. I raise this because occasionally an individual may have an adverse reaction to the supplement itself (e.g. pork, if the pepsin included is porcine in origin). I would also look carefully for coincidental changes: perhaps if you were feeling better from the higher HCl dose, you also expanded your diet or started consuming more of a particular food which might be a trigger for the eczema? What I most suspect is that the rapidly increased acidity from the HCl support has significantly reduced the pH of the chyme that flows into your intestines which can (1) increase overall digestion/absorption and/or (2) significantly change the microbiome. For example, we know that moving away from an excessively alkaline environment in the intestines can make it less hospitable to endemic yeast species. When we damage or kill off certain species in the gut, this can release potentially inflammatory microbial debris (e.g. LPS) or release harbored toxins (potentially increasing inflammation in the gut or in the systemic body if there is already intestinal… Read more »