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Leptin Resistance, Weight Loss Difficulty and Hypothyroidism

For those with hypothyroidism, leptin resistance can cause never-ending hunger and another layer of difficulty in losing weight.
Leptin Resistance, Weight Loss Difficulty and Hypothyroidism
Last updated:
9/15/2023
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If you’re trying to lose weight – especially if you have Hashimoto’s thyroiditis or hypothyroidism – it often feels like a difficult challenge. You’re not imagining it. It’s not just that your thyroid can negatively affect your metabolic rate. There’s also a hormone – leptin – that controls your hunger levels and fat burning. When your brain stops responding to it – a condition called leptin resistance – weight loss becomes an almost impossible challenge. In this article, learn about the role of leptin, leptin resistance, the relationship between leptin and the thyroid, the signs and symptoms of leptin resistance, and what can do to overcome the impediments to achieving a healthy weight.

What is leptin?

Leptin is a hormone produced by adipose tissue (body fat) that helps regulate body weight on a long-term basis. Leptin mainly communicates with the hypothalamus to regulate hunger and energy balance, providing the sensation of satiety (feeling full).

Leptin is often called the “satiety hormone” or the “starvation hormone” because it sends signals to your brain that help you feel full and less interested in food.

Leptin doesn’t affect your hunger levels and food intake from meal to meal. Still, it directly affects your food intake and energy expenditure over an extended period to help you maintain a healthy weight.

What is leptin resistance?

When everything is functioning normally, leptin tells your brain when enough fat is stored and sends the brain the message that you’re full, which prevents overeating and aids in healthy calorie burning.

But in some cases, the brain doesn’t respond to leptin. This condition is called leptin resistance.

Some of the causes of leptin resistance include:

  • Obesity: Obesity can lead to elevated leptin levels, which can cause leptin resistance
  • Hypothalamic Inflammation: Leptin works by sending signals to the hypothalamus, and studies suggest that people with obesity have increased inflammation in this area, which disrupts the hormone’s communication with the brain
  • Mutations in genes: Research has shown that mutations in the genes encoding leptin and its receptors, as well as proteins, can contribute to the development of leptin resistance
  • Lifestyle factors: Four lifestyle factors contribute to leptin resistance. They include too little sleep, too much stress, overconsumption of the wrong foods, and overeating in general.

Leptin resistance is an example of a broken feedback loop. The more you eat and gain weight, the more leptin increases, causing more leptin resistance. Your brain does not respond to leptin, so you don’t feel full and keep eating despite adequate or excessive fat stores, which leads to more weight gain and more leptin resistance.





Leptin resistance and thyroid conditions

When you have Hashimoto’s thyroiditis or hypothyroidism, you typically have higher leptin secretion, putting you at a higher risk of leptin resistance. In fact, hypothyroidism is one of the most common medical conditions associated with elevated serum leptin levels.

Studies have found that thyroid stimulating hormone (TSH) stimulates TSH receptors on the surface of fat cells, which directly increases leptin production.

A 2023 study found that serum leptin levels are higher in Hashimoto’s patients and significantly higher in people with hypothyroidism.

In another study of patients with hypothyroidism, serum leptin levels were significantly higher than in healthy euthyroid subjects. 

Symptoms of leptin resistance

Here are some of the symptoms of leptin resistance:

  • Weight gain, even with diet and exercise
  • Difficult losing weight – or an inability to lose weight -- despite eating a calorie-restricted diet and regular exercise
  • Increased appetite
  • Food cravings and hunger, even after eating
  • Cravings for sugary or high-fat foods
  • Fatigue or low energy levels
  • Difficulty sleeping or insomnia
  • Mood swings or irritability
  • Brain fog or difficulty concentrating
  • Joint pain or inflammation
  • High blood pressure or cholesterol levels

These symptoms may be more severe in people with Hashimoto’s or hypothyroidism.

Diagnosing leptin resistance

Leptin resistance is often a diagnosis based on a clinical evaluation of signs and symptoms. In some cases, healthcare providers may also order a serum leptin blood test, which measures the total leptin hormone concentration in your blood. According to the Cleveland Clinic, the reference range for leptin is 0.5 - 15.2 ng/mL for women and 0.5 - 12.5 ng/mL for men. Levels above 10 ng/mL are considered potential leptin resistance, and levels above 25 ng/mL are considered high, consistent with a leptin resistance diagnosis.

There is currently no specific medication or one-size-fits-all treatment for leptin resistance. Effectively reducing the degree of leptin resistance involves several approaches.

Thyroid treatment: If you’re hypothyroid, optimal treatment of your underactive thyroid with thyroid hormone replacement medication has been shown to reduce leptin secretion and help reverse the effects of leptin resistance. It is also essential to ensure adequate intake of micronutrients such as iron, selenium, and zinc, which are important for thyroid function.

Make dietary changes: Eating an anti-inflammatory diet low in sugar, simple carbohydrates, and processed foods – and higher in filling proteins and fiber -- may help reduce leptin resistance.

Intermittent fasting: According to research, intermittent fasting protocols can improve insulin resistance and sensitivity, as well as insulin resistance. It’s thought that fasting can reduce inflammation that causes leptin resistance and reset leptin receptors, encouraging weight loss.

Regular exercise: Physical activity may help reverse leptin resistance by lowering excess leptin levels. Specifically, research has found that endurance exercises like running or cycling can reduce leptin concentrations immediately after exercise and during rest. Resistance exercise such as weightlifting can also help lower leptin levels, although research shows that the effect may be delayed.

Get enough sleep: A lack of adequate sleep, poor sleep habits, and altered circadian rhythms can increase the risk for leptin resistance. Getting enough sleep – ideally, from 7 to 9 hours per night – can help to improve leptin sensitivity.

Try supplements: The herbs Cinnamomum cassia (Chinese cinnamon) and Gymnema Sylvestre may regulate appetite by influencing leptin, glucose, and insulin levels. Omega-3 fatty acids have been shown to reduce inflammation and improve insulin sensitivity, which may indirectly improve leptin sensitivity. Low vitamin D levels have been associated with obesity and insulin resistance, which can contribute to leptin resistance. Probiotics have been shown to improve gut health and reduce inflammation, which may indirectly improve leptin sensitivity.

Take medication: There are several prescription medications for type 2 diabetes that are used to target and reverse leptin resistance. These include Trulicity, Ozempic, Tanzeum, Lyxumia, Byetta, and Symlin. The type 2 diabetes drug Glucophage (metformin) appears to have some effects on leptin levels and leptin sensitivity, but the results are mixed. Several studies have found that metformin reduces leptin resistance, but other studies have found no significant effect on leptin levels. More research is needed to understand the relationship between metformin and leptin.

Practice stress reduction: Chronic stress can contribute to leptin resistance, so finding ways to manage stress, such as meditation, yoga, breathwork, or gentle exercise like tai chi, may be helpful.

A note from Paloma

As noted, hypothyroid patients won’t be able to resolve leptin resistance until they have optimal thyroid treatment and balanced thyroid hormones. Using the easy and convenient Paloma Complete thyroid test kit, you can monitor your progress with regular blood tests from home. While many labs only look only at Thyroid Stimulating Hormone (TSH) to assess thyroid function, Paloma Health believes it is also critical to measure Free Thyroxine (Free T4), Free Triiodothyronine (Free T3), and Thyroid Peroxidase Antibodies (TPOAb). You can also add on Reverse T3 and Vitamin D testing.

Since ensuring thyroid-friendly nutrient intake is an integral part of your thyroid treatment, Paloma’s Daily Thyroid Care supplement provides essential nutrients hypothyroid patients require for optimal thyroid gland function – including l-tyrosine, selenium, and zinc – in one easy-to-take capsule.

And because Paloma Health specializes in hypothyroidism, virtual visits with our team of trusted thyroid care providers ensure that you receive expert care in every aspect of your thyroid health.

With Paloma Health, you can get your blood tests, virtual visits, medical guidance, thyroid hormone prescriptions, and personalized care – all from the comfort of your own home!

Dealing with Hypothyroidism?  Video chat with a thyroid doctor

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References:

Gruzdeva O, Borodkina D, Uchasova E, Dyleva Y, Barbarash O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndr Obes. 2019 Jan 25;12:191-198. doi: 10.2147/DMSO.S182406. PMID: 30774404; PMCID: PMC6354688. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354688/

Upadhyaya P, Rehan HS, Seth V. Serum leptin changes with metformin treatment in polycystic ovarian syndrome: correlation with ovulation, insulin and testosterone levels. EXCLI J. 2011 Feb 24;10:9-15. PMID: 27857660; PMCID: PMC5109014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109014/

Oliveira, Luciana et al. Using Intermittent Fasting as a Non-pharmacological Strategy to Alleviate Obesity-Induced Hypothalamic Molecular Pathway Disruption. Front. Nutr., 30 March 2022. Sec. Nutrition, Psychology and Brain Health Volume 9 - 2022 | https://doi.org/10.3389/fnut.2022.858320 https://www.frontiersin.org/articles/10.3389/fnut.2022.858320/full

Tomov DG, Levterova BA, Troev DM, Miteva MZ, Mihaylova VN, Uzunova YI, Divarova VV, Orbetzova MM. Serum levels of leptin and adiponectin in patients with autoimmune Hashimoto’s thyroiditis. Folia Med (Plovdiv). 2023 Apr 30;65(2):199-206. doi: 10.3897/folmed.65.e75390. PMID: 37144303. https://foliamedica.bg/article/75390/

Oge A, Bayraktar F, Saygili F, Guney E, Demir S. TSH influences serum leptin levels independent of thyroid hormones in hypothyroid and hyperthyroid patients. Endocr J. 2005 Apr;52(2):213-7. doi: 10.1507/endocrj.52.213. PMID: 15863950. https://pubmed.ncbi.nlm.nih.gov/15863950/

El Amrousy, D., El-Afify, D. & Salah, S. Insulin resistance, leptin and adiponectin in lean and hypothyroid children and adolescents with obesity. BMC Pediatr 22, 245 (2022). https://doi.org/10.1186/s12887-022-03318-x
https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-022-03318-x

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Mary Shomon

Patient Advocate

Mary Shomon is an internationally-recognized writer, award-winning patient advocate, health coach, and activist, and the New York Times bestselling author of 15 books on health and wellness, including the Thyroid Diet Revolution and Living Well With Hypothyroidism. On social media, Mary empowers and informs a community of more than a quarter million patients who have thyroid and hormonal health challenges.

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