Overtesting & Overuse of Supplement Protocols in Functional Medicine

Guest Case Study by Dr. Robert Abbott

• Michael is a 62 year old male with a PMHx of hyperlipidemia who seeks support in optimizing his health and mitigating the negative effects of quarterly air travel to Asia. His only major symptoms include improving nocturia and frequent urination as well as a couple of musculoskeletal complaints including occasional lower back pain and a history of L5 spondylolisthesis. He has no contributory GI Sxs.
• He previously saw an out of state functional medicine practitioner who performed extensive testing summarized below.

1. Diagnostic Solutions GI MAP – Benign with no major findings. No notable insufficiency dysbiosis, opportunistic pathogens or digestive insufficiency.

2. Genova Diagnostics ION Profile – Slight increased need for zinc, no other major findings.

3. Precision Analytical DUTCH Complete Profile – Low normal free cortisol with normal cortisol metabolites, low normal morning free cortisol, low normal testosterone- blood chemistry later showed normal total and free testosterone. Normal organic acids.

4. Spectracell Cardiometabolic Panel– Reveals markedly, but positively discordant LDL Particle Count (1327 nmol/L) to LDL-C (218 mgdL) and Total Cholesterol (310 mg/dL). HDL Particle count is low. Lipoprotein (a) is suboptimal at 42.4 mg/dL. Insulin, homocysteine, hs-CRP, hemoglobin a1c and triglycerides are normal.

Note: I am not personally familiar with Spectracell’s Cardiometabolic Panel and I am suspicious that the lipoprotein markers are incorrect as they appear inconsistent with results from a NMR Lipoprofile through Labcorp earlier in 2019.

5. Basic blood chemistry – High normal Na, elevated Cl, low normal CO2, low normal Total T3 and Free T3 compared to Total T4 and Free T4. Less than optimal RDW.

Testing and Clinical Summary

On his GI MAP, the patient showed no clinically significant or correlative findings and is without GI symptoms. The patient had no major clinical indication for the GI MAP test. On his DUTCH profile, the patient showed low normal free cortisol and a low normal free morning cortisol peak as well as low normal testosterone. Future blood testing showed normal total and free testosterone. The patient endorsed no clinically correlative fatigue, cognitive fatigue, decreased exercise tolerance, frequent infections or a high level of perceived stress. The DUTCH Complete profile was an arguably reasonable test without clinically significant findings in my opinion. On his Genova Diagnostics ION profile, the patient showed low normal zinc with otherwise no major clinical findings. The Genova Diagnostics ION profile was an arguably reasonable test with essentially only one marginally helpful clinical finding. On the patient’s Spectracell Cardiometabolic Panel there appeared to be significant, but positive discordance between LDL-P and LDL-C with low normal HDL-P and otherwise normal markers of blood sugar and inflammation. The test, however, seemed inconsistent in some areas compared to a previous NMR lipoprofile performed early in 2019. The Spectacell’s Cardiometabolic Panel was a clinically appropriate test for this patient, however, I have great concern about this test’s complete accuracy and the cost of the profile as compared to equivalent wholesale blood chemistry through a reputable lab such as Labcorp is significantly higher and unwarranted. On the patient’s basic blood chemistry, we noted some less than optimal electrolytes alongside low normal Total and Free T3. Basic blood chemistry is the best starting point for most patients. This patient received a full thyroid profile with antibodies that was arguably not indicated.

Outside Clinician’s Original Assessment and Plan

The patient was diagnosed with “Stage III adrenal fatigue”, told to stop coffee, consume a morning cocktail of lemon water and apple cider vinegar and placed on a slew of adrenal products including hormonal replacement of DHEA and pregnenolone with an initial plan for 6 months of intensive treatment. He was additionally recommended to complete a comprehensive herbal antimicrobial protocol including liquid Biocidin, a silver product and additional antimicrobials. Despite the potentially concerning lipid profile, the patient was instructed to continue following a ketogenic style diet and no comment was made or treatment recommended for his dyslipidemia and associated cardiac risk.

My Commentary

What I have provided for you above is a detailed example of the misguided approaches of some functional medicine specialists performing numerous functional tests at baseline and recommending months worth of expensive supplements including supplements that are entirely not clinically indicated. I was appalled by the recommendations to follow an herbal antimicrobial protocol when the patient had no significant symptom burden, had not even used probiotics and had an unremarkable GI MAP test. He noted during our visit that he enjoyed coffee with mild to moderate consumption and still did not understand the rationale for removing it from his diet. No attention was given to his cardiometabolic testing, which, for an individual seeking optimization, is one of the 2 primary areas of concern outside of assessing and limiting cancer risk. While arguments could be made for the scope of testing recommended, we can all likely agree it was excessive even for an individual seeking optimization. If we are to be taken seriously in the functional medicine community, clinical care as I have described above must be greatly refined.

Visit 1 – History and Exam

I evaluated the patient approximately 6 weeks after the testing described previously.

Initial Impression

• The patient is slightly overweight, but fit reporting robust financial means and openness to nearly any therapy. He continues to be without major symptom burden or high stress. He does not endorse a significant understanding of previous testing and asks for some better clarification regarding the previous tests.

Visit 2 – Testing and Initial Recommendations

Testing

• Tests ordered:
  • NMR Lipoprofile
  • Lipoprotein (a) (repeat)
  • Glycomark
  • Fasting Insulin (repeat)
  • Hemoglobin A1c (repeat)
  • CBC (repeat)
  • CMP (repeat), Uric Acid, GGT, Phosphorous, LDH
  • Iron Profile

Rationale

As previously discussed, I had many concerns with the Spectracell’s Cardiometabolic Panel. Given the relatively low wholesale cost of the labs, I chose to repeat some of the cardiometabolic markers with the addition of Glycomark and the NMR lipoprofile for better comparison with the very first expanded lipid test he had performed about 1 year prior. I repeated the CBC and CMP given the abnormal findings on the first test for better trend analysis. I added an iron profile that was not previously performed.

• Imaging ordered:
  • Cardiac CT for Calcium Scoring

Rationale

Given his age, previous lipid findings and lack of previous imaging, I suggested performing a Cardiac CT for Calcium Scoring to help risk stratify him with regards to his risk for a cardiovascular event over the next 5-10 years. This would also provide further insight into the dietary protocols we may recommend and pursue.

Recommendations

• We discussed significantly modifying his current supplemental protocol including stopping the herbal antimicrobials and almost all of the adrenal supplements. I did not make any major dietary recommendations at this time as he will be seeing the nutritionist in the near future. We focused on slight tweaks to his exercise regimen, encouraged a slight decrease in the use of photobiomodulation and increased use of cryotherapy.

Rationale

There was no clinical indication for either a complex “adrenal fatigue” protocol or an herbal antimicrobial protocol. We sought to strengthen his lifestyle foundation while also optimize his use of available technologies including cryotherapy and photobiomodulation.

Visit 3 – Lab Interpretation and Treatment Evaluation

Lab Interpretation:

Summary

As expected, the NMR Lipoprofile showed a more concerning lipid profile with an elevated and negatively discordant LDL-P to LDL-C ratio with high normal number of small LDL-P. He has even less HDL-P on this test than previously and the lipoprotein (a) is now markedly elevated. While blood sugar indices including fasting insulin, hemoglobin A1c, and the newly tested Glycomark are within normal limits, the NMR lipoprofile and lipoprotein (a) are certainly concerning.

The Cardiac CT for Calcium Scoring showed an optimal score of 0 Agatson units. Without a calcium score, his 10-year risk for a cardiovascular event was between 6-7.5%. With the 0 calcium score, his risk decreased to 2-3%.

https://www.mesa-nhlbi.org/MESACHDRisk/MesaRiskScore/RiskScore.aspx

Subjective Assessment:

• Michael has had no major changes in his health. He appreciated the simplification in supplements and explanation of the testing.

Impression:

• With our lipid testing, we found markedly different findings for his blood lipids that put him into a higher risk categorization. We should be very wary of specialty labs and also be sure to do our due diligence of trending labs using standardized technology or methods to provide the best clinical utility. With the addition of the Cardiac CT Calcium Scoring (low radiation, $150) we properly categorized this non-smoking, non-diabetic patient as low risk for a cardiac event over the next 10 years.

Recommendations:

• Visit with a nutritionist to explore optimization of his dietary pattern, fasting, etc
• Repeat blood chemistry at 3-month intervals

Visit 4

Subjective Assessment:

• Continues to feel good following a nutrient dense ketogenic diet. He is also desiring support in preparation for travel and eager to incorporate fasting into his regimen.

Impression:

• Prepared for maintenance supplementation with modified fasts during air travel and simplified fasting mimicking diet after his return. We will closely monitor any changes in his lipids over the next 3-6 months as well as his quality of life, but overall have provided a greatly simplified hands off approach to his wellness.

Recommendations:

• Vitamin A, D, E K complex
• Mitochondrial support supplement
• Adaptogen complex as desired in morning, encourage use during travel
• Omega 3 supplement
• Boulardii probiotic

Dr. Ruscio’s Comments

Amazing job Rob.  Admittedly, there are times when I feel I am being overly circumspect regarding functional medicine testing.  I try not to let the knowledge that I have in my areas, GI and thyroid, regarding the rampant follies of testing spill over into other areas, this could be a false conflation.  However, examples like this reinforce the generally suspicious nature I revert to.  The bottom line here, sadly, is that much functional medicine testing is not clinically helpful but will distress patients and expose them to unneeded treatment and worry – thus are more harmful than beneficial. 

Probiotics Protect Against Cold, Flu, and Respiratory Tract Infection

https://drruscio.com/probiotics-protect-against-cold-flu-and-respiratory-tract-infection/

Study Purpose

• Review data illustrating probiotics can protect against cold, flu and URTI (upper respiratory tract infections).

Intervention:

• Review, non-systematic

Main Results:

• Multiple reviews have found probiotics are more effective than placebo in
  • Duration of illness (URTI) and prevention
  • Abx use
• Treatments used
  • Various blends (Lact/Biff) and forms (food, capsules, powder) have been used
• Not all data agree, but there is a clear trend of benefit as supported by conclusions of review data.

Limitations:

• How well do these finding translate to the upper respiratory involvement from SARS/COVID-19 has not been determined.

Interesting Notes:

• See full post where I elaborate here
• The main data points to support my conclusions are listed below
  • Cochrane database systematic review “Probiotics for preventing acute upper respiratory tract infections.”
    • Probiotics were found to be better than placebo in reducing the number of participants experiencing episodes of acute upper respiratory tract infections. The mean duration of an episode and the amount of antibiotics that were used in this kind of cold/flu related way. So their conclusion,
    • “This indicates that probiotics may be more beneficial than placebo for preventing acute URTIs. However, the quality of the evidence was low or very low.”
  • Systematic review with meta-analysis from the British Journal of Nutrition “Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis.”
    • In this study they looked at evidence from a number of high quality randomized control trials and they found that the duration of illness of common acute respiratory infections in otherwise healthy children and adults was reduced. Additionally, 10 of these studies were conducted in adults of which two were conducted in elderly. So this finding does seem to permeate all age groups.
    • “This systematic review provides evidence from a number of good-quality RCT that probiotics reduce the duration of illness (common acute respiratory infectious) in otherwise healthy children and adults.”
  • Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies” published in the Journal of Evidence-based Complementary and Alternative Medicine.
    • “Probiotics were found better than placebo in reducing the number of episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use.” 
  • “Bifidobacterium bifidum R0071 results in a greater proportion of healthy days and a lower percentage of academically stressed students reporting a day of cold/flu: a randomised, double-blind, placebo-controlled study.”
    • “The proportion of participants reporting a cold on any given day was lower […] in the B. bifidum and B. infantis than with placebo for the average level of stress and the most commonly reported number of hours of sleep.”
    • So what they did there was they tried to control for stress and sleep. Obviously this is a great setup because increased stress and sleep deprivation could certainly confound the results. So by kind of stratifying the participants into tiers of sleep and of stress and looking at the effect of the intervention versus the control among those groups, we have a more apple to apple comparison. Leading them to conclude,
    • “Daily intake of bifidobacteria provides benefit related to cold/flu outcomes during acute stress.”
  • “The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: a systematic review and meta-analysis of randomized controlled trials.”
    • “Concomitant prebiotics or probiotics supplementation with influenza vaccination may hold great promise for improving vaccine efficacy. However, high heterogeneity was observed and further studies are warranted.”

Clinical Takeaways:

• Probiotics prevent and reduce cold flu episode, duration, severity and associated antibiotic use. 
• What to tell your patients:
  • Probiotics strengthen your immune system and help you fight the cold/flu virus.

Dr. Ruscio Comments

Obviously this post is meant to provide insights regarding probiotics’ potential role in the COVID pandemic.

Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much?

J Crohn’s Colitis. 2015 Feb;9(2):198-209.

Study Purpose

• Review data regarding vitamin D for IBD

Intervention:

• Review, non-systematic

Main Results:

• 2 studies have found vitamin D to improved Crohn’s. There are 8 (1, 2, 3, 4, 5, 6, 7, 8) published clinical studies/trials for UC with vitamin D injections or supplements which are preliminary positive but no meta-analysis or systematic review yet published, only reviews (1, 2).
  • To date, only two small open label trials and one randomized controlled trial have shown a positive effect of vitamin D supplementation on disease activity in patients with CD; no effect has been shown for UC.
  • Only two small open label trials (with 37 and 18 patients, respectively) and one randomized controlled trial (RCT) (with 104 patients) have analyzed the effects of vitamin D supplementation on disease activity in patients with CD (88, 89, 90) but there have been no clinical trials in patients with UC.
  • To date, no clinical trials have evaluated the effect of vitamin D supplementation on disease activity in patients with UC.
• Optimal blood levels have not yet been determined but might be between 30-50 ng/mL (US unites).
  • An optimal vitamin D supplementation protocol for patients with IBD remains undetermined, but targeting serum 25-hydroxy vitamin D [25(OH)D] levels between 30 and 50 ng/mL appears safe and may have benefits for IBD disease activity.
• Daily dose between 2,000 to 10,000 IUs per day may be required dose. Note: I usually recommend a maintenance dose of 2,000 IU/day and a treatment dose of 10,000 IU/day.
  • vitamin D doses between 1 800–10,000 international units/day are probably necessary.

Additional Results:

• Vitamin D supplementation reduces relapse in quiescent Crohn’s
  • A multicentre, randomized, double-blind placebo-controlled trial evaluating vitamin D maintenance therapy in 108 CD patients in clinical remission (CDAI score < 150) found that treatment with 1200 IU/day vitamin D3 for 3 months improved vitamin D status significantly compared with placebo (88) After a follow-up of 12 months, disease relapse rates were lower in the vitamin D than in the placebo group (29% versus 13%, p = 0.06).

Limitations:

• No data yet looking at UC.
• Only two trials for Crohn’s.

Authors Conclusion:

• Vitamin D supplementation and saturation of 25(OH)D3 reserves may be a novel therapeutic approach in patients with IBD, an approach that is simple, effective, safe and inexpensive. Preliminary preclinical and clinical data suggest that vitamin D has therapeutic potential in IBD, particularly in CD.

Interesting Notes:

• Mechanistic diagram on immunomodulatory effects of vitamin D
  
• Other data support colorectal cancer risk reduction with higher vitamin D levels or intake
  • A meta-analysis of five studies revealed that patients with serum 25(OH)D levels ≥ 33 ngl/L had a 50% lower risk of CRC than patients with 25(OH)D levels ≤12 nmol/L (101).
  • Furthermore, vitamin D intake of 1,000 IU/day was associated with a 50% lower CRC risk than intake of <100 IU/day (102).

Clinical Takeaways:

• Preliminary data suggest vitamin D supplementation improves IBD, namely Crohn’s. 
• Optimal intake and levels of vitamin D appears to reduce colorectal cancer risk
• What to tell your patients:
  • Obtaining healthy (30-50 ng/mL) levels of vitamin D may improve IBD, specifically Crohn’s, and may also protect against colorectal cancer.

Dr. Ruscio Comments

Something to monitor in IBD patients and a rather cheap, simple and non-invasive intervention for GI health.  Remember other preliminary data also suggest vitamin D improves IBS.

Treatment of refractory and severe hypothyroidism with sublingual levothyroxine in liquid formulation.

Endocrine. 2018 Apr;60(1):193-196. doi: 10.1007/s12020-017-1367-5. Epub 2017 Jul 13.

Study Purpose

• Assess impact of sublingual dosing of liquid thyroid hormone medication in those not optimally absorbing it through oral dosing.

Intervention:

• Case series

Main Results:

• Restoration of euthyroidism was achieved after switching from tablet to liquid L-T4
  • Here we report three cases of patients with severe hypothyroidism and persistent TSH increase despite the administration of high doses of tablet L-T4. Hypothyroid-ism suddenly improved and euthyroidism was progressively restored in these patients after sublingual administration of L-T4 in liquid formulation
    
• No adverse events were reported
  • Our patients did not complain any local or systemic adverse event after the sublingual administration of L-T4. They did not report cardiac arrhythmias or any ECG alterations or gastrointestinal adverse effects.

Additional Results:

• Liquid T4 medications may circumvent poor GI absorption
  • Novel oral formulations of L-T4 have been developed to improve this problematic issue. Oral liquid L-T4 formula-tions and soft gel capsules are useful in patients with con-temporary assumption of L-T4 with food or beverages during breakfast, pharmacological interferences, and gas-trointestinal disorders [8, 9, 10, 11, 12, 13]. They can improve the L-T4 assimilation in patients with and without malabsorption [12]
• Certain medication will limit absorption of thyroid HRT, including acid suppressors.
  • The contemporary ingestion of drugs (iron, sucralfate, calcium carbonate, antiacids, and prompton pump inhibitors) may reduce L-T4 absorption [1, 4, 5].
• Healthy GI function is required for thyroid Rx absorption – This is why so many thyroid patients do not require meticulous testing/treatment but rather improved GI competency
  • Moreover, malabsorption of L-T4 may occur in patients with gastrointestinal disorders such as coeliac disease [1], Helicobacter pylori infection [5], congestive gastropathy, autoimmune gastritis [6], short bowel syndrome [1], lactose intolerance [7], and chronic giardiasis [1].

Limitations:

• Small number of subjects

Authors Conclusion:

• We can conclude that the sublingual administration of L-T4 may be a safe alternative method for acute treatment of severe hypothyroidism, compared to the parenteral L-T4 administration.

Interesting Notes:

• Certain medications interfere with thyroid absorption
  • Only 70–80% of the L-T4 administered dose is absorbed [3, 4, 5] and a normal gastric acid secretion environment is needed to allow an adequate L-T4 assimilation [1, 2, 3, 4, 5], which occurs within the first 90 min after tablet ingestion [3, 5].
• The starting optimal replacement dose of L-T4 related to body weight (BW) is about 1.6–1.8 µg/kg/d in hypothyroid adults [1].

Clinical Takeaways:

• In those who only partially respond to liquid L-T4 (ie: Tirosint) dosing liquid L-T4 sublingual may yield to normalization of thyroid hormone levels.
• What to tell your patients:
  • Absorption of your medication should be our first priority before we evaluate down-stream metabolites or conversion. First make sure the car has gas, then worry about the gas mileage.

Dr. Ruscio Comments

More data supporting the importance of GI-health and absorption of thyroid medication.

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

Effect of probiotic supplementation in pregnant women: A meta-analysis of randomized controlled trials.

Br J Nutr. 2020 Apr 28;123(8):870-880. doi: 10.1017/S0007114519003374. Epub 2019 Dec 20.

• A total of eighteen randomized controlled trials (RCT) including 4356 pregnant women were eligible.
• Probiotic supplementation was associated with a significant decrease in the risk of
  • Atopic eczema (RR 0·68; 95 % CI 0·58, 0·81; P < 0·001)
  • Eczema (RR 0·79; 95 % CI 0·68, 0·91; P = 0·002)
  • Probiotic supplementation was associated with a prolonged gestational age
• whereas no significant effect was exerted on birth weight (P = 0·851).
• The risks of death and necrotizing enterocolitis were significantly reduced in pregnant women receiving probiotics

These findings suggested that probiotics in pregnant women were beneficial for atopic eczema, eczema, gestational age, death and NEC.