Toxins are so widely distributed within our environment that even for those of us that are conscious of limiting our exposure, total avoidance is simply impossible. This is demonstrated with a population study in the United States finding 100% detection of urinary phthalate metabolites in men, women and children.¹ As the literature on the impact of environmental toxins on human health grow, naturopaths, nutritionists and integrative medicine practitioners will be at the forefront for developing and implementing treatment strategies to combat this impact and improve the health of our patients.

Whilst there is an array of environmental toxins that clinicians need to be familiar with, this case study focuses on the disruption of male hormones by phthalates and the subsequent consequences to the patient’s overall health. In fact, well-indicated treatments didn’t have their intended effect until the bioaccumulation of phthalates was addressed.

Phthalates are a diverse group of industrial compounds that are the most widely produced plasticisers. In some plastics, phthalates comprise up to 50% of the total weight. However, phthalates are also widely found in personal care products such as shampoo, deodorant and body wash as well as paints, adhesives, vinyl flooring, cables, and enteric-coated pharmaceuticals and nutritional tablets.²

The decline in testosterone levels in men over the past half-century has been attributed to increasing male obesity, however, Mazur et al (2013) used an unusually large and lengthy longitudinal study to determine that whilst indeed the testosterone decline was intensified with weight gain, the findings excluded obesity as the primary explanation.³

Phthalates have been shown to be associated with significantly reduced testosterone in both sexes and differing age groups. In adult men, a significant inverse association between phthalates and testosterone has been observed among men ages 40–60 years.¹

Presenting Symptoms

A 42-year-old male presented with fatigue that had been persistent for several years. Onset was hard for him to pinpoint but was associated with weakness and reduced muscle mass. He was unable to exercise as even light exertion would exacerbate his fatigue for 2 to 3 days. Additionally, he had been experiencing ‘foggy brain’ that was worse when his energy levels were low.

Systems Review

The patient had a history of reflux and had been on medication, Rabeprazole, but had ceased 4 months prior.

He frequently experienced loose stool up to 2 to 3 times per day and was intermittently associated with increased abdominal bloating and discomfort.

He was married with two children but had recognised that the fatigue was really having an impact on his libido. He had been taking Epimedium sagittatum (Horny Goat Weed) that he has purchased at a health food store, but it hadn’t helped at all. His work had started to suffer because of fatigue and brain fog. He had been having bouts of depression, but he found it difficult at times to separate the fatigue, brain fog and mood.

He experiences a lot of muscle aches and pains, which he would manage by taking Ibuprofen.

Sleep onset was problematic as he would often have a ‘busy mind’ and have trouble switching off. He was very restless at bedtime and would have trouble getting comfortable. He regularly had cramps in his calves at night.

Primary Health Goals:

• Improve sleep
• Enhance vitality
• Improve fatigue and body composition
• Improve digestion and bowel movements
• Enhance cognitive function and mood

Initial Prescription:

• Magnesium powder containing 315 mg elemental Magnesium plus Carnitine, B vitamins, Taurine, Glutamine, and Zinc: ½ scoop twice daily.
• Herbal sleep formula containing Lavandula angustifolia (Lavender), Piper methysticum (Kava) and Withania somnifera (Withania): 2 tablets at bedtime.
• Referral to GP for blood tests.
• Review appointment (3 weeks)
• Sleep improved dramatically. He was falling asleep much quicker and was experiencing improved quality sleep, waking more refreshed than in the past.

Key Pathology Findings:

CAPTION: Acronyms: HDL: High density lipoprotein cholesterol; LDL: Low density lipoprotein cholesterol; SHBG: Sex hormone binding globulin; DHEA: Dehydroepiandrosterone

The test results indicated low testosterone as a primary therapeutic target. Vitamin D was low and is a factor in testosterone levels in men. Not only has vitamin D deficiency been associated with lower testosterone, Pilz et al⁴ also showed that vitamin D supplementation improved testosterone levels in vitamin D deficient men when given 3332 IU daily for 12 months.

Zinc is another important nutrient for testosterone production, and whilst I prefer serum copper: zinc ratios as the ideal assessment, the test results did not highlight zinc as a concern.

Elevated ferritin has long been associated with inflammatory diseases and noted to provide protection against free radicals in oxidative stress. More recently, accumulation of iron has also been implicated in obesity, cancer, aging, and progression of chronic neurodegenerative conditions, such as Alzheimer and Parkinson disease.⁵

Metabolic syndrome was confirmed for this patient with:

• High risk waist circumference 105 cm
• Blood pressure: 135/90 mm Hg
• Elevated triglycerides > 1.7 mmol/L

Treatment Plan

1. Improve testosterone levels as a key component to improving presenting symptoms
2. Reduce inflammation and oxidative stress
3. Address metabolic syndrome

Prescription updates:

• Reduce herbal sleep formula to 1 tablet at night
• Reduce Magnesium & B complex powder to ½ scoop at night
• Add Tribulus terrestris (Tribulus) containing 13.5 dried herb: 1 tablet, three times daily
• Vitamin D3: 5000 IU daily
• Iron-free multivitamin containing a unique nutritional profile including B vitamins, Lithium, Rubidium, Cobalt, and Betaine Hydrochloride

Review appointment (8 weeks)

Generally, the patient was feeling some improvement (self-rated 2/10). His sleep had continued to improve, which he felt was contributing to feeling better. No change in physical strength, libido or ability to exercise.

Test results showed no improvements in testosterone levels or free testosterone. His GP was considering testosterone hormone replacement.

I referred the patient for salivary oestrone and oestradiol to identify if excessive aromatase activity was a consideration in this case. I also referred the patient for a urinary environmental pollutant panel. The results excluded high aromatase activity/excess estrogen but did show high phthalate exposure as indicated by urinary metabolites:

Phthalates are eliminated through glucuronidation, predominantly via the urine, and to a lesser extent, the gut and through sweat. Increasing perspiration has been shown to increase elimination of phthalates. Genuis et al6 demonstrated that whilst not all metabolites, some parent phthalate compounds and metabolites are readily excreted in sweat and infrared saunas may play a valuable role in reducing bioaccumulation.

Treatment interventions:

1. Reduce exposure
   • Food packaging
   • Personal care products
   • Selective use of organic foods - prioritise high fat foods plus dirty dozen
   • Occupational exposure - computer/IT
2. Increase elimination^6,7
   • Induce sweating through infrared saunas
   • Include sources of glucuronic acid (required by glucuronidation) including Chondroitin, fermented foods (kombucha) and Glycyrrhiza glabra (Licorice)
   • Increase Magnesium levels as it is a co-factor for glucuronidation
   • Increase Green tea, Rosemary, Quercetin, Curcumin and Fish Oil consumption to promote glucuronidation
3. Avoid medications that inhibit glucuronidation i.e., non-steroidal anti-inflammatory drugs (NSAIDs)

Prescription update:

Continue with previous supplements adding:

• Infrared sauna, 3 times per week
• Herbal tablet containing Vitis vinifera (Grape Seed), Camellia sinensis (Green Tea), Curcumin longa (Turmeric), and Salvia Rosmarinus (Rosemary): 1 tablet, twice daily
• Tablet containing Glucosamine 750 mg, Chondroitin Sulfate 205 mg and Boron 1.5mg; 1 tablet, daily
• Add kombucha to diet

Response to Treatment:

Once the detoxification processes where supported, there was a marked and noticeable change in the symptom presentation almost immediately. Whilst energy levels improved incrementally, it was consistent and substantial. He noticed a difference in his muscle mass and he had been able to start light exercise with no exacerbations in symptoms. The improvements were associated with improvement in testosterone levels as determined by follow-up testing over a 12-month period.

Ongoing treatment has now been re-focused to addressing inflammation, reducing ferritin and managing metabolic syndrome, though improving testosterone and muscle mass has already started to improve some of these parameters.

Conclusion

This case really highlighted the importance of a holistic approach is in addressing toxin exposure. Whilst reducing exposure is advised, complete avoidance is impossible as exposure is ubiquitous with living in the modern world. Naturopaths, nutritionist and integrative medicine have an important role in highlighting not only the impact of environmental toxins, but in helping patients understand how to limit exposure. Our in-depth understanding of liver detoxification pathways and application of nutritional and herbal treatments, can positively and profoundly impact the health of our patients.

References

1. Meeker JD, Ferguson KK. Urinary Phthalate Metabolites Are Associated with Decreased Serum Testoerone in Men, Women and Children From NHANES 2011-2012. J Clin Endocrinol Metab. 2014; 99(11):4436-4352.
2. Saeidnia S. Phthalates, in Encyclopedia of Toxicology (3rd Ed), 2014. P 928-933. Elsevier Publishing.
3. Mazur A, et al. Is Rising Obesity Causing a Secular (Age-Independent) Decline in Testosterone among American Men? PLosOne 2013, 8(10): e76178
4. Pilz S, et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. 2011; 43(3): 223-225
5. Mahroun N, et al. Ferritin – from iron, through inflammation and autoimmunity, to COVID-19. J Autoimmun. 2022; 126: 102778.
6. Genuis SJ, et al. Human Elimination of Phthalate Compounds: Blood, Urine and Sweat (BUS) Study. Sci World J. 2012; 615068.
7. Hodges Re, Minich D. Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: a scientific review with clinical application. J Nutr Metab; 2015: 760689