Future of Functional Medicine Review Clinical Newsletter

Practical Solutions for Practitioners – March 2020

Dr. Michael Ruscio’s Monthly – Future of Functional Medicine Review Clinical Newsletter

Medically reviewed & fact checked by a
board-certified doctor
Medically reviewed & fact checked by a
board-certified doctor
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Histamine Intolerance, Medication Reduction & Lifestyle Changes Resolve a ‘Chronic & Complex’ Case

Guest Case Study by Dr. Ronit Mor

Patient Info:

  • First Name: Ellen
  • Age: 43
  • Dx:
    • Fibromyalgia
    • Hashimoto’s hypothyroidism
    • POTS syndrome
    • Insulin resistance / pre-diabetes
    • Endometriosis / PCOS / uterine fibroids
    • Fatty liver
    • Osteoarthritis
    • Barrett’s Esophagus
    • Sleep apnea
    • Atypical cystic fibrosis (CFTR)
    • Candida
    • 12 to 15 white matter brain lesions
    • Ehlers-Danlos syndrome hypermobility
    • Elevated PAI-1 (high risk of stroke heart attack and blood clots)
    • Hemochromatosis carrier
    • Beta thalassemia carrier
    • ADHD
  • Rx (8 different physicians):
    • Bioidentical hormone replacement therapy: testosterone, pregnenolone, progesterone, DHEA, 5-HTP, T3.
    • Metformin
    • Ajovy migraine shots regularly
    • Every 12 weeks: 30 botox shots over the head and back of the neck
    • Xopenex and Xopenex HFA
    • Dexilant
    • Sucralfate
    • Hydrocortisone
    • Midodrine
    • Acebutolol
    • Gabapentin
    • Naltrexone
    • Cyclobenzaprine
    • Budesonide
    • Dymista
    • Liothyronine
    • Levalbuterol
    • Diflucan
    • Valtrex
    • 3 to 4 rounds of antibiotics a year
    • Annual flu vaccinations
  • Chief Complaints
    • Weight issues
    • Digestive issues (heartburn, alternate constipation/diarrhea, daily flatulence/gas/bloating, hemorrhoids)
    • Chronic hemiplegic migraines
    • Excessive fatigue/extremely low energy levels
    • Chronic muscle and joint pain
    • Heart palpitations and high heart rate
    • Hormonal imbalance (based on repeated comprehensive hormonal panels)
    • Frequent sinus infections
    • Frequent kidney stones
    • Frequent UTI’s
    • Anxiety
    • Constant brain fog and difficulty focusing
    • Severe sleep issues
    • Endometriosis
    • Severe allergies
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Visit 1 - 9/5/2019 – History and Exam

Previous and current procedures/operations:

  • Three sinus surgeries to remove nasal polyps, complete sinus scrapes, opening of upper sinus
  • Three tonsillectomies

History of Complaints:

  • Hemiplegic migraines along with regular migraines started sometime in high school. When she gets the hemiplegic ones she has a hard time talking and usually right arm and right leg weakness. Sometimes hard to walk, lots of weakness and fatigue. It can last anywhere from one to 4 days then often the whole cycle starts all over again. Lately, they are more under control with chiropractic care. She receives Ajovy migraine shots regularly and every 12 weeks 30 botox shots over the head and back of the neck.
  • Heartburn started in 1995 after her brother died in a car accident. She’s been on meds off and on since 1995 and has had several endoscopies over the years. It got a lot worse in 2017. That’s when she was diagnosed with stomach pre-cancer/intestinal metaplasia. Her next endoscopy was positive for Barrett’s Esophagus.
  • She’s had painful periods for years. To the point where she passes out and is bedridden with body pain and migraines and very painful cramps.
  • In 2006 after the birth of her second child, her thyroid antibodies shot up to the 800’s. An ultrasound confirmed multiple thyroid nodules. She was put on Synthroid. In April 2019, she had a thyroid biopsy at UT Southwestern on an irregular shaped thyroid nodule. It was negative. In May of 2019, she was taken off of Synthroid and was put on BHRT (see above notes).
  • In 2010 she started getting frequent sinus infections and bronchitis, literally every other month and they were hard to clear. She had 3 sinus surgeries. After her 3rd sinus surgery to remove polyps, she was sent to an Immunologist and then to a CF clinic. She was then diagnosed with Atypical Cystic Fibrosis (also known as CFTR Related Disorder).
  • Severe symptoms of allergies since 2010. She was allergy tested twice, blood and skin tests, and no allergies were found except for an ash tree (which doesn’t even grow in this area of Texas).
  • She has had 5 calcium kidney stones since 2010.
  • Severe aches and pains since 2013. In 2017, her rheumatologist diagnosed her with fibromyalgia and osteoarthritis. She ruled out lupus and Sjogren’s.
  • In 2017, she was diagnosed with POTS. She’s had heart palpitations since high school. It picked up again in her 30’s and got a lot worse in 2013. Since 2014 she has been also short of breath has had high heart rate.Taking meds and seeing an electrophysiologist regularly.
  • Diagnosed with sleep apnea 2 months ago.

Initial Impression 

Reviewed health history, labs, MyBodyScore results, nutrition and lifestyle habits with client. Collected detailed information regarding current complaints, progression of complaints over the years, and nutrition and lifestyle habits.

Client is depressed, anxious, and lost most hope of ever feeling well again. She feels that she is unable to function as a wife and a mother anymore. She is overwhelmed with the amount and complexity of her issues, the number of different physicians she has to see on a regular basis, and the number of medications and side effects from these medications. She is suspecting that some of her issues are due to side effects and also due to the recent BHRT she was placed on a few months ago.

Client expressed her readiness to take a fresh look at her state of health and explore a root cause approach rather than the traditional approach she has taken thus far.

Testing:

MyBodyScore (score = 14) assessment:

Score = 14 out of 100

Potential Primary Stressors: chronic dehydration, multiple moderate to high nutrient deficiencies, food sensitivities (gluten/lectins), histamine intolerance, dysbiosis, oxidative stress, oral health, MTHFR, heavy metals, neuromusculoskeletal markers.

Potential Secondary Stressors: systemic inflammation, sluggish detoxification pathways (lymph, colon, kidneys, liver), sluggish adrenals and thyroid, hormonal imbalance.

Recent labs: imbalanced thyroid panel, imbalanced hormonal panel, elevated viral markers, positive candida, normal HA1c, low cholesterol, low HDL, elevated hs-CRP.

Lifestyle factors:

Weight: obese (236 lbs/5’7”).

Hydration habits: 160 oz daily intake (ideal for her weight is 120 oz).

Sun exposure habits: zero sun exposure. – love the attention to this

Nutrition habits: high-carb, high-histamine, high-lectins, mostly gluten-free (except for sourdough bread daily), highly processed (mainly due to GF products and protein bars), light to moderate sugar content.

Initial Observations:

Potential root causes at the core of complaints: multiple drugs/procedures, improper nutrition, low cholesterol, nutrient deficiencies, food sensitivities (gluten/lectins), histamine intolerance, dysbiosis, neuromusculoskeletal issues, inflammation.

Initial Recommendations: 

  • Correct hydration to net 120 oz daily water intake
  • Improve water source quality
  • Implement first set of nutrition/lifestyle guidelines (30-day elimination of gluten, lectins, and high-histamine foods).
  • Implement the following supplement plan:
    • Systemic Enzyme Complex by Pure Encapsulations
    • B Complex Plus by Seeking Health
    • Trace Mineral Complex II Iron by Seeking Health
    • Copper Free by Seeking Health
    • EPA/DHA essentials 1000mg by Pure Encapsulations
    • Bone CoFactors by Douglas Labs
    • Histamine Block by Seeking Health
    • Ashwagandha by Pure Encapsulations
    • During bouts of low blood pressure and lightheadedness, also: Hawthorne Max-V 250mg by Douglas Labs and Potassium 99mg Chelated by Douglas Labs.
  • Referred to: PCP Dr. Russ Skinner
  • Additional labs: thyroid panel
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Visit 2 - 9/19/2019 – Brief Checkpoint

Subjective Assessment: 

Client is doing well, following guidelines and taking supplements. She is already noticing the connection between high-histamine foods and some of her symptoms. She feels very good about the program and is excited to start working with Dr. Skinner.

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Visit 3 - 10/11/2019 – Progress Review

Subjective Assessment: 

Client seems to be more energetic, positive and upbeat.

Dr. Skinner: Client had her first appointment with him today. I was present at that meeting and we mutually agreed that it’s time to start making Rx changes.

Current Rx: Discontinued Metformin and BHRT. Switched to Armour. Weaning off steroids.

Dr. R’s note: Key change here – reducing the amount of hormones and moving from T3 only to a combination of T4 and T3. My take is it’s best to start with T4, but this is not an absolute rule and the underlying principle still applies; reduce unneeded medications (testosterone, DHEA, etc.) and regarding thyroid, ensure T4 is being addressed, as many problems with T3 are secondary to something else (in this case histamine intolerance and presumed inflammation). 

New labs: low T4, low RT3, low FT4.

Current hydration habits: about 120 oz daily intake

Current nutrition habits: has been following elimination diet

Current Supplements: taking all supplements

Other treatments in the past four weeks: weekly chiropractic care

Reported improvement since last visit:

  • Weight issues – lost 6 lbs
  • Digestive issues – heartburn resolved, alternate constipation/diarrhea resolved, flatulence/gas/bloating resolved, hemorrhoids improved
  • Chronic migraines – significantly improved
  • Excessive fatigue – significantly improved
  • Muscle pain, joint pain – significantly improved
  • Heart palpitations and high heart rate – comes and goes
  • Frequent sinus infections – none in the past month
  • Frequent UTI’s – none in the past month
  • Anxiety – resolved
  • Brain fog – significantly improved
  • Difficulty focusing – improved
  • Sleep issues – significantly improved, sleeping much better
  • New complaint: hair loss
    • From Dr. R: look at all these improvements from making the right changes. The patient is taking fewer supplements and drugs, yet feeling better. In functional/natural medicine, more is not better. 

Recommendations: 

  • Continue following the elimination of gluten, lectins, and high-histamine foods.
  • Additional guidelines were provided in regard to protein and fat intake as well as a few lifestyle factors.
  • Per Dr. Skinner: start gradual elimination of steroids and switch from BHRT to Armour.
  • Additional labs: thyroid panel in 2 months.
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Visit 4 - 12/13/2019 – Progress Review

Subjective Assessment: 

Client is thriving. Most symptoms resolved. Energy up. Feeling very well. Very happy and hopeful.

Current Rx: discontinued Metformin, steroids, and BHRT. Switched to Armour. Weaning off Dexilant and Acebutolol.

New labs: normal thyroid panel

Current hydration habits: about 120 oz daily intake

Current nutrition habits: has been following the elimination diet

Current Supplements: taking all supplements

Other treatments in the past four weeks: weekly chiropractic care

Reported improvement since last visit:

  • Weight issues – lost 18 lbs since the beginning of the program
  • Digestive issues – heartburn resolved, alternate constipation/diarrhea resolved, flatulence/gas/bloating resolved, hemorrhoids resolved
  • Chronic migraines – resolved
  • Excessive fatigue – resolved
  • Muscle pain – improved
  • Joint pain – resolved
  • Heart palpitations and high heart rate – significantly improved, saw Dr. Rajit Abrol with Heart Place Plano (electrophysiologist) and he was amazed with her improvement and took her off Acebutol
  • Frequent sinus infections – resolved
  • Frequent UTI’s – a mild episode of unexplained bladder pain but other than that no issues
  • Anxiety – resolved
  • Brain fog – resolved
  • Difficulty focusing – significantly improved
  • Sleep issues – resolved

Recommendations: 

  • Continue following elimination of gluten and lectins. May re-introduce certain high-histamine foods occasionally and in measure.
  • Additional guidelines were provided in regard to a few lifestyle factors.
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Visit 5 - 1/17/2020 – Brief Checkpoint

Subjective Assessment: 

Client is thriving. All symptoms (except for neck pain) resolved. Energy up. Feeling very well. Very happy and hopeful. She just scheduled both of her teenage kids to see me because they have similar symptoms to her symptoms prior to working with me.

Current Rx: Discontinued Metformin, steroids, Dexilant, Acebutolol, Ajovi, Botox shots and BHRT. Switched to Armour. Still taking pain meds for muscle pain.

Current hydration habits: about 120 oz daily intake

Current nutrition habits: Has been following the elimination diet, gradually reintroducing some high-histamine foods in extreme moderation and care.

Current Supplements: taking all supplements

Other treatments in the past four weeks: weekly chiropractic care

Reported improvement since last visit:

  • Weight issues – lost 22 lbs since the beginning of the program
  • Still has mild neck pain
  • All other symptoms resolved

Recommendations: 

  • Continue following nutrition/lifestyle guidelines and supplement plan.
  • Additional guidelines were provided in regard to a few lifestyle factors.
  • Referred to: Osteopathic doctor for osteopathic manipulative treatment.
  • Next steps: Complete wellness panel and progress review in 2 months.

Note: Months later, Ellen emailed to express how great she was feeling and how happy she was with her care.

Dr. Ruscio’s Comments 

What a great case illustrating the difference between treating the cause (diet, histamine, lifestyle…) versus the symptoms. Also, resolution of symptoms without requiring an array of lab tests. This type of care is how you build a busy, thriving practice full of happy patients. 

Bravo Dr. Mor. 


 

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RESEARCH REVIEW

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Systematic review: Quality of trials on the symptomatic effects of the low FODMAP diet for irritable bowel syndrome.

Aliment Pharmacol Ther. 2017 Jun;45(12):1506-1513. doi: 10.1111/apt.14065. Epub 2017 Apr 25.

Study Purpose

  • Review of the quality trials on the low FODMAP diet trials

Intervention:

  • Systematic review
  • Nine RCTs were eligible, including 542 patients.
  • A high risk of bias was identified
    • Domains with a high risk of bias were identified for all the trials. High risk of bias dominated domains regarding blinding, with only one trial double-blinded.
    • The risk of bias was assessed by the Cochrane collaborations tool.

Main Results:

  • 5 of 9 trials reported benefit from low FODMAP
  • 4 of the 9 reported no improvement over placebo.
    • Five of the nine trials reported a positive effect of the diet on IBS symptoms superior to the control intervention (9, 15, 17, 19, 20) and four trials reported an equivalent symptomatic effect of the low FODMAP diet compared with the control intervention.
  • Bias #1: The control diets, in some cases, were high FODMAP diets, thus potentially falsely inflating the positive impact of the LF, since control was high FODMAP.
    • In three trials all meals were provided to the study participants (9, 17, 20) The control meals reflected a typical Australian diet (9), a typical American childhood diet (17) and a high FODMAP diet (20). The FODMAP content in the typical Australian diet (24 g/d) exceeded the baseline FODMAP content (16 g/d) (9) and should therefore also be classified as a high FODMAP diet. The same applies to the typical American childhood diet (0.7 g/kg/d) (17) exceeding the FODMAP content of 12 g/d, as reported in the baseline diet of a comparable population in a study by the same authors (21).
  • Bias #2: A source of bias was due to monitoring symptoms (subjective outcomes) which inherently carry a risk of bias. However, I have some challenges with this as IBS does not have reliable biomarkers so a bias-laden subjective assessment might be the only way to evaluate this.
    • There was a high risk of performance bias in eight of the nine trials (Table S2). As the effect of the intervention relies primarily on subjective outcomes, the magnitude of performance bias is aggravated.
  • Bias #3: Another source of bias was due to patients being able to tell what diet they were on, you can visually see if high FODMAP foods are no longer allowed on your diet.
    • Dr. R’s note: Again, however, I’m not sure that this is a bias that can easily be designed out of a trial that maintains a degree of real-world applicability. We could, in theory, give participants a baseline low FODMAP diet and then give ½ capsules of placebo and the other ½ capsules of a high FODMAP pill. However, that loses the more real-world impact of assessing food changes in the diet.
  • Bias #4: Appears to be a difficult thing to design out of dietary trials, especially IBS trials. This is evidenced by the fact that even the standard dietary advice appears at risk of bias.
    • Unfortunately, standard of care dietary advice is also based on limited evidence (24).
    • There is a high placebo response in treatment trials of IBS patients, regardless of the character of the intervention (28). The placebo response ranges from 3% to 84% in published IBS treatment trials (29). In a meta-analysis of 76 placebo-controlled drug trials in IBS, Ford et al. found placebo rates between 0% and 91 (30).
  • Bias #5: The impact of a low FODMAP diet may only have applicability in a narrowed setting (tertiary care) and may lack applicability in primary care. And is based upon smaller trials.
    • The RCTs included small numbers of patients primarily recruited from tertiary care, which may compromise the ability to generalize. They included patients from tertiary care and breath test centers constituting a selected population that might be especially motivated for dietary intervention. Furthermore, there is a lack of trials investigating the effects of the diet in IBS patients in primary care, with only one study recruiting a limited number (4%) of patients from primary care (14).

Authors Conclusion:

  • The recommendation of the low FODMAP diet as a first-line treatment for patients with IBS is based on randomized interventional trials characterized by high risk of bias, primarily due to lack of proper blinding and choice of control group.
  • There are many indications in the published literature to suggest that the symptomatic effects of the low FODMAP diet are primarily driven by a placebo response.

Interesting Notes:

  • Wheat, dairy and onions were found to be the most avoided foods in one long-term follow-up study.
    • A limited characterization of reintroduced foods was described in a retrospective questionnaire study (32). At 15 months follow-up, 84% of patients lived on a modified diet with some foods rich in FODMAPs and wheat; dairy products and onions were least often reintroduced (32).

Clinical Takeaways:

  • High-level scientific evidence has found that low FODMAP diet benefits IBS patients
  • These results also carry a high risk of bias.
  • To guard against this, maintain objectivity when counseling patients on the low FODMAP diet.
  • What to tell your patients:
    • The low FODMAP diet can be helpful for those with digestive symptoms. However, it is not helpful for all patients so it is important to approach this objectively and listen to your body.
    • We will also work to heal your gut and thus allow you to expand your diet over time.

Dr. Ruscio Comments

The piece on bias here is important to be aware of, the better we understand the limitations of the science, the more accurately we can speak to a diet’s potential effect and comment on it with our patients.

A more recent meta-analysis in the journal Nutrition concluded that a low FODMAP diet is beneficial, but made no mention of bias in the abstract. However, full-text reports: Overall, risk of bias of the included studies was unclear. Only three studies [out of nine] reported adequate blinding of outcome assessment  and a generally high risk was found for performance bias.

The critique that an LF diet’s improvements could be driven by placebo exemplifies how important it is that providers attempt to strike an objective middle-ground when discussing diet with their patients. On the one hand, a bit of optimizing can be helpful for a struggling patient. On the other hand, we should avoid indoctrinating patients.


 

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Microbiota and Thyroid Interaction in Health and Disease.

Trends Endocrinol Metab. 2019 Aug;30(8):479-490. doi: 10.1016/j.tem.2019.05.008. Epub 2019 Jun 27.

Study Purpose

  • Review data regarding the gut-thyroid connection

Intervention:

  • Review, non-systematic

Main Results:

  • While tempting, a definitive tie between the gut and hypothyroid has not yet been determined
    • Current data do not support the hypothesis of a microbiota composition specific for thyroid diseases.
  • The authors cite a study finding treating SIBO with Rifaximin did not impact the LT4 dose. However, one other interesting study did find that probiotics could decrease the dose of T4 needed, so what might be happening here is there is malabsorption that is not SIBO-dependent but which does improve from probiotics.
    • On the other hand, doses of L-thyroxine therapy to normalize T4 levels in hypothyroid patients with SIBO did not significantly differ from hypothyroid patients without SIBO [47].
  • Zinc deficiency impacts thyroid hormone levels
    • Zn deficiency reduces free T3 and T4 levels by 30% in animals [29]. In humans TSH, T4, and T3 serum levels are also decreased by Zn deficiency, hypothyroid individuals frequently present with low serum Zn levels [30].
    • It appears that the relationship between Zn and thyroid metabolism is reciprocal because hypothyroidism induces Zn deficiency and insufficient supplementation with Zn causes hypothyroidism.
  • Gut bacteria compete with the host for selenium, as we have discussed prior.
    • These minerals also have prominent roles influencing the gut microbiota. Bacteria compete with the host for Se. Resident microbes of the colon metabolize the Se, which is not absorbed by the host in the upper GI tract [31].
  • Dr. R’s note: those with hypothyroid have a roughly 30% chance of hypochlorhydria, this is likely why low ferritin is more prevalent in this cohort.
    • Iron is absorbed as Fe (II) mainly in the duodenum, where the pH is acidic (pH ~6.0).
  • The authors site data related hypothyroid to bile and SIBO.
    • Bile acids regulate energy metabolism via changes in TSH levels, and total bile acid levels in blood were decreased in patients with subclinical hypothyroidism [45]
    • The higher levels of secondary bile acids in hypothyroidism may result from the fact that small intestinal bacterial overgrowth (SIBO) is common in patients with hypothyroidism [47].
  • Thus, I penned a diagram as food for thought (please excuse typos and penmanship). AIT – autoimmune thyroid, APCA – anti-parietal cell antibodies.
    r2-01.png
  • There is a potential embryonic link between thyroid autoimmunity and gastric (parietal) autoimmunity.
    • The coincidence of both diseases may be explained by the common embryonic origin of thyroid follicular cells and gastric mucosal cells because the thyroid gland develops from primitive gut cells [51]. Both cells also share the ability to take up I− and they express similar peroxidases (gastric peroxidase and thyroperoxidase).
  • Table comparing overlap of autoimmune diseases, see the caption for abbreviations
    r2-02.png
  • The association between pylori and AIT is inconsistent, as we have discussed
    • Although dysbiosis is a known predisposing factor for AIDs in general, colonization with Helicobacter pylori has been linked only to AMAG and GD, and disparate reports of an association between Helicobacter pylori and HT have been published [51].

Additional Results:

  • More iodine is not better, too much or too little pose a problem
    • Severe iodine deficiency is linked to hypothyroidism, mild to moderate deficiencies cause multifocal autonomous growth of the thyroid, and excess of iodine is associated with thyroid autoimmunity [7].
  • Autoimmune thyroid diseases are the most prevalent organ-specific autoimmune diseases and affect 2–5% of the population. But their support for this statement is poor, one study in Graves’. Other data contradict this finding.
    • In both autoimmune thyroid diseases (AITDs) the severity of the disease is not correlated to antibody levels. Furthermore, anxiety and depression in GD are not linked to thyroid function or thyroid autoimmunity [11].
  • Authors make another interesting remark, but with no reference. I’ll attempt to find it and list below.
    • Direct effects on mood by thyroid hormones are unlikely because subclinical hyperthyroidism is associated with better mood compared to euthyroid subjects. [13, 14]
  • Disruptions in gut bacteria were noted in mood disorders.
    • An abundance of Actinobacter and Enterobacteriacae was noted in all mood disorders, whereas Faecalibacterium spp. were decreased [12] relative to the distribution of phyla (see classification of bacteria) in the normal gut (Box 2).

Limitations:

  • This study made some contentious claims with no reference and made definitive sounding claims based upon sparse evidence, not the best review I have seen.

Interesting Notes:

  • Authors claim that thyroid antibody levels do not correlate with sequela of anxiety or depression.
    • In both autoimmune thyroid diseases (AITDs) the severity of the disease is not correlated to antibody levels. Furthermore, anxiety and depression in GD are not linked to thyroid function or thyroid autoimmunity [11].

Clinical Takeaways:

  • The gut-thyroid connection exists but is still not fully understood
  • Some symptoms might be GI-driven and not from the thyroid
  • What to tell your patients:
    • It is important we look to your gut health as a potential cause or contributor to your thyroid health and symptoms.

Dr. Ruscio Comments

The main point here I would like to emphasize is the hypothyroid-hypochlorhydria-SIBO connection. This is something I am paying closer attention to after the podcast with Dr. Richar McCallum and his finding that SIBO might be more of a top-down phenomenon than a colonic refluxing of bacteria up into the SI.


 

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Personalized Nutrition by Prediction of Glycemic Responses.

Cell. 2015 Nov 19;163(5):1079-1094. doi: 10.1016/j.cell.2015.11.001.

Study Purpose

  • Evaluate if a microbiota-base assessment can be more effective in managing blood glucose than a diet guided by glycemic index.

Intervention:

  • “We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals.
  • We validated these predictions in an independent 100-person cohort.
  • Finally, a blinded randomized controlled dietary intervention based on this algorithm resulted in significantly lower postprandial responses and consistent alterations to gut microbiota configuration.”
    r3-01.png

Main Results:

  • “Together, our results suggest that personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences.”
  • Highlights
    • High interpersonal variability in post-meal glucose observed in an 800-person cohort
    • Using personal and microbiome features enable accurate glucose response prediction
    • Prediction is accurate and superior to common practice in an independent cohort
    • Short-term personalized dietary interventions successfully lower post-meal glucose
  • The test-guided diet outperformed a nutritionist/glycemic-index-guided-diet. **Note: This is the type of data we need to justify a test, for contrast, most gene-testing-studies of this type have failed to show gene-guided interventions are better than control interventions**
    • Next, we asked whether personally tailored dietary interventions based on our algorithm could improve PPGRs.
    • We designed a two-arm blinded randomized controlled trial and recruited 26 new participants.
    • A clinical dietitian met each participant and compiled 4–6 distinct isocaloric options for each type of meal (breakfast, lunch, dinner, and up to two intermediate meals), accommodating the participant’s regular diet, eating preferences, and dietary constraints.
    • Participants then underwent the same 1-week profiling of our main 800-person cohort (except that they consumed the meals compiled by the dietitian), thus providing the inputs (microbiome, blood parameters, CGM, etc.) that our algorithm needs for predicting their [postprandial (post-meal) glycemic responses] PPGRs.
  • Dr. R’s note: My interpretation of this study is as follows
    • Using glycemic index works about as well for predicting a ‘good foods’ impact on blood glucose.
    • However, for foods with higher glycemic indices (‘bad foods’), it appears the prediction/test-guided diet, has a better effect on blood glucose.
    • Said more simply – the testing can help you determine what higher glycemic index foods risk a more or less negative impact on your blood sugar.

Additional Results:

  • I have not taken a hard stance on post-prandial glucose (PPG) levels in the office, it’s not an area I focus on. I also questioned if meticulous monitoring was necessary. I still question this as I feel looking at practical endpoints may be more efficient; weight, energy, FBG, HA1c.   However, the authors make an interesting point here – also see chart below (in short PPG correlates with other important measures; BMI, HA1c)
    • These associations (between post-prandial glucose levels and morbidity) are not confined to extreme values but persist along the entire range of PPGR values, suggesting that the reduction in levels of risk factors is continuous across all postprandial values, with lower values associated with lower levels of risk factors even within the normal value ranges (Figure 2A)
      r3-02.png
  • A higher degree of variability between individuals BS response to a given food was noted:
    • “…when comparing the PPGRs of different people to the same meal, we found high interpersonal variability, with the PPGRs of every meal type (except fructose) spanning the entire range of PPGRs measured in our cohort (Figures 2B)”.

Limitations:

  • Preliminary data, first of its kind. However, they have continued to refine the data and published data in 5 other articles and collaborate with a product Day Two: “The product is based on a five-year research conducted by Prof. Eran Segal and Prof. Eran Elinav from the Weizmann Institute of Science in Israel; the research was funded solely by the Weizmann Insitute of Science and upon its completion, the research technology was licensed to DayTwo.”

Interesting Notes:

  • “up to 70% of prediabetics eventually developing the disease (Nathan et al., 2007). It is also linked to other manifestations, collectively termed the metabolic syndrome, including obesity, hypertension, non-alcoholic fatty liver disease, hypertriglyceridemia, and cardiovascular disease”.
  • “Indeed, studies examining the effect of diets with a low glycemic index on TIIDM risk, weight loss, and cardiovascular risk factors yielded mixed results (Greenwood et al., 2013; Kristo et al., 2013; Schwingshackl and Hoffmann, 2013).”
  • The post-prandial glucose response to foods is highly variable
    • “More broadly, ascribing a single PPGR to each food assumes that the response is solely an intrinsic property of the consumed food. However, the few small-scale (n = 23–40) studies that examined interpersonal differences in PPGRs found high variability in the response of different people to the same food (Vega-Lopez et al., 2007; Vrolix and Mensink, 2010), but the factors underlying this variability have not been systematically studied.”

Clinical Takeaways:

  • The commercial version of this test, Day Two, may further enhance an individual’s blood sugar regulation.
  • What to tell your patients:
    • This is a very interesting test with preliminary evidence validating its use. It is not a test we ‘start’ with, but once we are in the refinement/optimization phase, it makes sense to consider.

Dr. Ruscio Comments

See our podcast with lead researcher Dr. Elan Erinav here.

Follow up validation has been performed by lab Day Two. This is one of the few microbiota assays that has been validated.


 

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Rapid-Fire Research: Ultra-Concise Summaries of Noteworthy Studies

Systematic review with meta-analysis: the prevalence of small intestinal bacterial overgrowth in inflammatory bowel disease.

Aliment Pharmacol Ther. 2019 Mar;49(6):624-635. doi: 10.1111/apt.15133. Epub 2019 Feb 8.

  • Overall, there is a substantial increase in the prevalence of SIBO in IBD patients compared to controls. Prior surgery and the presence of fibrostenosing disease are risk factors for SIBO in IBD.

The Convergence of Bacterial Overgrowth, Systemic Inflammatory Biomarkers, and Anti-Vinculin Antibodies in Determining the Response to Rifaximin Treatment in Diarrhea-Predominant IBS (D-Ibs) Subjects

https://ep70.eventpilot.us/web/page.php?page=IntHtml&project=DDW18&id=2918438

  • Conclusions: In this study, breath testing remains the strongest predictor of response to rifaximin in D-IBS. However, the addition of systemic inflammatory molecules and AbV to breath testing improved the prediction of response to rifaximin. Further studies are needed to determine the ideal predictors of response to therapy in IBS-D patients.
    • Note: In short, Vinculin and CtdB testing don’t enhance antibiotic treatment.

Discussion

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